Single molecules and nanotechnology

CERN Document Server

Vogel, Horst

2007-01-01

This book focuses on recent advances in the rapidly evolving field of single molecule research. These advances are of importance for the investigation of biopolymers and cellular biochemical reactions, and are essential to the development of quantitative biology. Written by leading experts in the field, the articles cover a broad range of topics, including: quantum photonics of organic dyes and inorganic nanoparticles their use in detecting properties of single molecules the monitoring of single molecule (enzymatic) reactions single protein (un)folding in nanometer-sized confined volumes the dynamics of molecular interactions in biological cells The book is written for advanced students and scientists who wish to survey the concepts, techniques and results of single molecule research and assess them for their own scientific activities.

On Single-Valued Neutrosophic Entropy of order α

Directory of Open Access Journals (Sweden)

Harish Garg, Nancy

2016-12-01

Full Text Available Entropy is one of the measures which is used for measuring the fuzziness of the set. In this article, we have presented an entropy measure of order α under the single-valued neutrosophic set environment by considering the pair of their membership functions as well as the hesitation degree between them. Based on this measure, some of its desirable properties have been proposed and validated by taking an example of structure linguistic variable.

Parametric scaling from species relative abundances to absolute abundances in the computation of biological diversity: a first proposal using Shannon's entropy.

Science.gov (United States)

Ricotta, Carlo

2003-01-01

Traditional diversity measures such as the Shannon entropy are generally computed from the species' relative abundance vector of a given community to the exclusion of species' absolute abundances. In this paper, I first mention some examples where the total information content associated with a given community may be more adequate than Shannon's average information content for a better understanding of ecosystem functioning. Next, I propose a parametric measure of statistical information that contains both Shannon's entropy and total information content as special cases of this more general function.

Single Molecule Electronics and Devices

Science.gov (United States)

Tsutsui, Makusu; Taniguchi, Masateru

2012-01-01

The manufacture of integrated circuits with single-molecule building blocks is a goal of molecular electronics. While research in the past has been limited to bulk experiments on self-assembled monolayers, advances in technology have now enabled us to fabricate single-molecule junctions. This has led to significant progress in understanding electron transport in molecular systems at the single-molecule level and the concomitant emergence of new device concepts. Here, we review recent developments in this field. We summarize the methods currently used to form metal-molecule-metal structures and some single-molecule techniques essential for characterizing molecular junctions such as inelastic electron tunnelling spectroscopy. We then highlight several important achievements, including demonstration of single-molecule diodes, transistors, and switches that make use of electrical, photo, and mechanical stimulation to control the electron transport. We also discuss intriguing issues to be addressed further in the future such as heat and thermoelectric transport in an individual molecule. PMID:22969345

Colloidal lenses allow high-temperature single-molecule imaging and improve fluorophore photostability

Science.gov (United States)

Schwartz, Jerrod J.; Stavrakis, Stavros; Quake, Stephen R.

2010-02-01

Although single-molecule fluorescence spectroscopy was first demonstrated at near-absolute zero temperatures (1.8 K), the field has since advanced to include room-temperature observations, largely owing to the use of objective lenses with high numerical aperture, brighter fluorophores and more sensitive detectors. This has opened the door for many chemical and biological systems to be studied at native temperatures at the single-molecule level both in vitro and in vivo. However, it is difficult to study systems and phenomena at temperatures above 37 °C, because the index-matching fluids used with high-numerical-aperture objective lenses can conduct heat from the sample to the lens, and sustained exposure to high temperatures can cause the lens to fail. Here, we report that TiO2 colloids with diameters of 2 µm and a high refractive index can act as lenses that are capable of single-molecule imaging at 70 °C when placed in immediate proximity to an emitting molecule. The optical system is completed by a low-numerical-aperture optic that can have a long working distance and an air interface, which allows the sample to be independently heated. Colloidal lenses were used for parallel imaging of surface-immobilized single fluorophores and for real-time single-molecule measurements of mesophilic and thermophilic enzymes at 70 °C. Fluorophores in close proximity to TiO2 also showed a 40% increase in photostability due to a reduction of the excited-state lifetime.

Single Molecule Analysis Research Tool (SMART: an integrated approach for analyzing single molecule data.

Directory of Open Access Journals (Sweden)

Max Greenfeld

Full Text Available Single molecule studies have expanded rapidly over the past decade and have the ability to provide an unprecedented level of understanding of biological systems. A common challenge upon introduction of novel, data-rich approaches is the management, processing, and analysis of the complex data sets that are generated. We provide a standardized approach for analyzing these data in the freely available software package SMART: Single Molecule Analysis Research Tool. SMART provides a format for organizing and easily accessing single molecule data, a general hidden Markov modeling algorithm for fitting an array of possible models specified by the user, a standardized data structure and graphical user interfaces to streamline the analysis and visualization of data. This approach guides experimental design, facilitating acquisition of the maximal information from single molecule experiments. SMART also provides a standardized format to allow dissemination of single molecule data and transparency in the analysis of reported data.

Single-molecule dynamics in nanofabricated traps

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Cohen, Adam

2009-03-01

The Anti-Brownian Electrokinetic trap (ABEL trap) provides a means to immobilize a single fluorescent molecule in solution, without surface attachment chemistry. The ABEL trap works by tracking the Brownian motion of a single molecule, and applying feedback electric fields to induce an electrokinetic motion that approximately cancels the Brownian motion. We present a new design for the ABEL trap that allows smaller molecules to be trapped and more information to be extracted from the dynamics of a single molecule than was previously possible. In particular, we present strategies for extracting dynamically fluctuating mobilities and diffusion coefficients, as a means to probe dynamic changes in molecular charge and shape. If one trapped molecule is good, many trapped molecules are better. An array of single molecules in solution, each immobilized without surface attachment chemistry, provides an ideal test-bed for single-molecule analyses of intramolecular dynamics and intermolecular interactions. We present a technology for creating such an array, using a fused silica plate with nanofabricated dimples and a removable cover for sealing single molecules within the dimples. With this device one can watch the shape fluctuations of single molecules of DNA or study cooperative interactions in weakly associating protein complexes.

Single-photon sources based on single molecules in solids

International Nuclear Information System (INIS)

Moerner, W E

2004-01-01

Single molecules in suitable host crystals have been demonstrated to be useful single-photon emitters both at liquid-helium temperatures and at room temperature. The low-temperature source achieved controllable emission of single photons from a single terrylene molecule in p-terphenyl by an adiabatic rapid passage technique. In contrast with almost all other single-molecule systems, terrylene single molecules show extremely high photostability under continuous, high-intensity irradiation. A room-temperature source utilizing this material has been demonstrated, in which fast pumping into vibrational sidebands of the electronically excited state achieved efficient inversion of the emissive level. This source yielded a single-photon emission probability p(1) of 0.86 at a detected count rate near 300 000 photons s -1 , with very small probability of emission of more than one photon. Thus, single molecules in solids can be considered as contenders for applications of single-photon sources such as quantum key distribution

Single-Molecule Spectroscopy

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 2. Single-Molecule Spectroscopy: Every Molecule is Different! Kankan Bhattacharyya. General Article Volume 20 Issue 2 February 2015 pp 151-164. Fulltext. Click here to view fulltext PDF. Permanent link:

Preface: Special Topic on Single-Molecule Biophysics.

Science.gov (United States)

Makarov, Dmitrii E; Schuler, Benjamin

2018-03-28

Single-molecule measurements are now almost routinely used to study biological systems and processes. The scope of this special topic emphasizes the physics side of single-molecule observations, with the goal of highlighting new developments in physical techniques as well as conceptual insights that single-molecule measurements bring to biophysics. This issue also comprises recent advances in theoretical physical models of single-molecule phenomena, interpretation of single-molecule signals, and fundamental areas of statistical mechanics that are related to single-molecule observations. A particular goal is to illustrate the increasing synergy between theory, simulation, and experiment in single-molecule biophysics.

Pulsed IR Heating Studies of Single-Molecule DNA Duplex Dissociation Kinetics and Thermodynamics

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Holmstrom, Erik D.; Dupuis, Nicholas F.; Nesbitt, David J.

2014-01-01

Single-molecule fluorescence spectroscopy is a powerful technique that makes it possible to observe the conformational dynamics associated with biomolecular processes. The addition of precise temperature control to these experiments can yield valuable thermodynamic information about equilibrium and kinetic rate constants. To accomplish this, we have developed a microscopy technique based on infrared laser overtone/combination band absorption to heat small (≈10−11 liter) volumes of water. Detailed experimental characterization of this technique reveals three major advantages over conventional stage heating methods: 1), a larger range of steady-state temperatures (20–100°C); 2), substantially superior spatial (≤20 μm) control; and 3), substantially superior temporal (≈1 ms) control. The flexibility and breadth of this spatial and temporally resolved laser-heating approach is demonstrated in single-molecule fluorescence assays designed to probe the dissociation of a 21 bp DNA duplex. These studies are used to support a kinetic model based on nucleic acid end fraying that describes dissociation for both short (10 bp) DNA duplexes. These measurements have been extended to explore temperature-dependent kinetics for the 21 bp construct, which permit determination of single-molecule activation enthalpies and entropies for DNA duplex dissociation. PMID:24411254

Predictions of the entropies of molecules and condensed matter

International Nuclear Information System (INIS)

Blander, M.; Stover, C.R.

1992-01-01

In this paper, we discuss a statistical mechanical theory for calculating the standard nonelectronic entropies (S O T ) and free energy functions [(G O T --H O 298 )/T] of substances at high temperatures. These quantities are important and are often the only unknown data necessary for determining free energies of compounds, which is necessary for the calculation of chemical and phase equilibria. This lack of data is particularly significant at high temperatures that are important in the genesis of magmas and metamorphic rocks. Accurate enthalpies of formation of compounds are relatively easy to measure calorimetrically. In order to calculate the free energies of compounds from enthalpies of formation at different temperatures, one needs a knowledge of the entropies as a function of temperature. On the other hand, with a knowledge of the free energy functions of a compound as a function of temperature, one needs only a single measurement of the enthalpy of formation of that compound to determine the free energies over a range of temperatures. Thus, since there are very many substances for which such enthalpies of formation are the only known thermodynamic data, a major expansion of standard tables of free energies of formation is possible if one can predict entropies or free energy functions for these substances

Single-Molecule Interfacial Electron Transfer

Energy Technology Data Exchange (ETDEWEB)

Lu, H. Peter [Bowling Green State Univ., Bowling Green, OH (United States). Dept. of Chemistry and Center for Photochemical Sciences

2017-11-28

This project is focused on the use of single-molecule high spatial and temporal resolved techniques to study molecular dynamics in condensed phase and at interfaces, especially, the complex reaction dynamics associated with electron and energy transfer rate processes. The complexity and inhomogeneity of the interfacial ET dynamics often present a major challenge for a molecular level comprehension of the intrinsically complex systems, which calls for both higher spatial and temporal resolutions at ultimate single-molecule and single-particle sensitivities. Combined single-molecule spectroscopy and electrochemical atomic force microscopy approaches are unique for heterogeneous and complex interfacial electron transfer systems because the static and dynamic inhomogeneities can be identified and characterized by studying one molecule at a specific nanoscale surface site at a time. The goal of our project is to integrate and apply these spectroscopic imaging and topographic scanning techniques to measure the energy flow and electron flow between molecules and substrate surfaces as a function of surface site geometry and molecular structure. We have been primarily focusing on studying interfacial electron transfer under ambient condition and electrolyte solution involving both single crystal and colloidal TiO₂ and related substrates. The resulting molecular level understanding of the fundamental interfacial electron transfer processes will be important for developing efficient light harvesting systems and broadly applicable to problems in fundamental chemistry and physics. We have made significant advancement on deciphering the underlying mechanism of the complex and inhomogeneous interfacial electron transfer dynamics in dyesensitized TiO₂ nanoparticle systems that strongly involves with and regulated by molecule-surface interactions. We have studied interfacial electron transfer on TiO₂ nanoparticle surfaces by using ultrafast single-molecule

Communication: Probing the absolute configuration of chiral molecules at aqueous interfaces

Energy Technology Data Exchange (ETDEWEB)

Lotze, Stephan, E-mail: lotze@amolf.nl; Versluis, Jan [FOM Institute for Atomic and Molecular Physics, Science Park 104, 1098 XG Amsterdam (Netherlands); Olijve, Luuk L. C.; Schijndel, Luuk van; Milroy, Lech G.; Voets, Ilja K. [Laboratory of Macromolecular and Organic Chemistry, Department of Chemical Engineering and Chemistry, and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven (Netherlands); Bakker, Huib J., E-mail: bakker@amolf.nl [FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam (Netherlands)

2015-11-28

We demonstrate that the enantiomers of chiral macromolecules at an aqueous interface can be distinguished with monolayer sensitivity using heterodyne-detected vibrational sum-frequency generation (VSFG). We perform VSFG spectroscopy with a polarization combination that selectively probes chiral molecular structures. By using frequencies far detuned from electronic resonances, we probe the chiral macromolecular structures with high surface specificity. The phase of the sum-frequency light generated by the chiral molecules is determined using heterodyne detection. With this approach, we can distinguish right-handed and left-handed helical peptides at a water-air interface. We thus show that heterodyne-detected VSFG is sensitive to the absolute configuration of complex, interfacial macromolecules and has the potential to determine the absolute configuration of enantiomers at interfaces.

Single-molecule dataset (SMD): a generalized storage format for raw and processed single-molecule data.

Science.gov (United States)

Greenfeld, Max; van de Meent, Jan-Willem; Pavlichin, Dmitri S; Mabuchi, Hideo; Wiggins, Chris H; Gonzalez, Ruben L; Herschlag, Daniel

2015-01-16

Single-molecule techniques have emerged as incisive approaches for addressing a wide range of questions arising in contemporary biological research [Trends Biochem Sci 38:30-37, 2013; Nat Rev Genet 14:9-22, 2013; Curr Opin Struct Biol 2014, 28C:112-121; Annu Rev Biophys 43:19-39, 2014]. The analysis and interpretation of raw single-molecule data benefits greatly from the ongoing development of sophisticated statistical analysis tools that enable accurate inference at the low signal-to-noise ratios frequently associated with these measurements. While a number of groups have released analysis toolkits as open source software [J Phys Chem B 114:5386-5403, 2010; Biophys J 79:1915-1927, 2000; Biophys J 91:1941-1951, 2006; Biophys J 79:1928-1944, 2000; Biophys J 86:4015-4029, 2004; Biophys J 97:3196-3205, 2009; PLoS One 7:e30024, 2012; BMC Bioinformatics 288 11(8):S2, 2010; Biophys J 106:1327-1337, 2014; Proc Int Conf Mach Learn 28:361-369, 2013], it remains difficult to compare analysis for experiments performed in different labs due to a lack of standardization. Here we propose a standardized single-molecule dataset (SMD) file format. SMD is designed to accommodate a wide variety of computer programming languages, single-molecule techniques, and analysis strategies. To facilitate adoption of this format we have made two existing data analysis packages that are used for single-molecule analysis compatible with this format. Adoption of a common, standard data file format for sharing raw single-molecule data and analysis outcomes is a critical step for the emerging and powerful single-molecule field, which will benefit both sophisticated users and non-specialists by allowing standardized, transparent, and reproducible analysis practices.

Searching for Next Single-Phase High-Entropy Alloy Compositions

Directory of Open Access Journals (Sweden)

David E. Alman

2013-10-01

Full Text Available There has been considerable technological interest in high-entropy alloys (HEAs since the initial publications on the topic appeared in 2004. However, only several of the alloys investigated are truly single-phase solid solution compositions. These include the FCC alloys CoCrFeNi and CoCrFeMnNi based on 3d transition metals elements and BCC alloys NbMoTaW, NbMoTaVW, and HfNbTaTiZr based on refractory metals. The search for new single-phase HEAs compositions has been hindered by a lack of an effective scientific strategy for alloy design. This report shows that the chemical interactions and atomic diffusivities predicted from ab initio molecular dynamics simulations which are closely related to primary crystallization during solidification can be used to assist in identifying single phase high-entropy solid solution compositions. Further, combining these simulations with phase diagram calculations via the CALPHAD method and inspection of existing phase diagrams is an effective strategy to accelerate the discovery of new single-phase HEAs. This methodology was used to predict new single-phase HEA compositions. These are FCC alloys comprised of CoFeMnNi, CuNiPdPt and CuNiPdPtRh, and HCP alloys of CoOsReRu.

Fluorescent Biosensors Based on Single-Molecule Counting.

Science.gov (United States)

Ma, Fei; Li, Ying; Tang, Bo; Zhang, Chun-Yang

2016-09-20

Biosensors for highly sensitive, selective, and rapid quantification of specific biomolecules make great contributions to biomedical research, especially molecular diagnostics. However, conventional methods for biomolecular assays often suffer from insufficient sensitivity and poor specificity. In some case (e.g., early disease diagnostics), the concentration of target biomolecules is too low to be detected by these routine approaches, and cumbersome procedures are needed to improve the detection sensitivity. Therefore, there is an urgent need for rapid and ultrasensitive analytical tools. In this respect, single-molecule fluorescence approaches may well satisfy the requirement and hold promising potential for the development of ultrasensitive biosensors. Encouragingly, owing to the advances in single-molecule microscopy and spectroscopy over past decades, the detection of single fluorescent molecule comes true, greatly boosting the development of highly sensitive biosensors. By in vitro/in vivo labeling of target biomolecules with proper fluorescent tags, the quantification of certain biomolecule at the single-molecule level is achieved. In comparison with conventional ensemble measurements, single-molecule detection-based analytical methods possess the advantages of ultrahigh sensitivity, good selectivity, rapid analysis time, and low sample consumption. Consequently, single-molecule detection may be potentially employed as an ideal analytical approach to quantify low-abundant biomolecules with rapidity and simplicity. In this Account, we will summarize our efforts for developing a series of ultrasensitive biosensors based on single-molecule counting. Single-molecule counting is a member of single-molecule detection technologies and may be used as a very simple and ultrasensitive method to quantify target molecules by simply counting the individual fluorescent bursts. In the fluorescent sensors, the signals of target biomolecules may be translated to the

Electrochemically-gated single-molecule electrical devices

International Nuclear Information System (INIS)

Guo, Shaoyin; Artés, Juan Manuel; Díez-Pérez, Ismael

2013-01-01

In the last decade, single-molecule electrical contacts have emerged as a new experimental platform that allows exploring charge transport phenomena in individual molecular blocks. This novel tool has evolved into an essential element within the Molecular Electronics field to understand charge transport processes in hybrid (bio)molecule/electrode interfaces at the nanoscale, and prospect the implementation of active molecular components into functional nanoscale optoelectronic devices. Within this area, three-terminal single-molecule devices have been sought, provided that they are highly desired to achieve full functionality in logic electronic circuits. Despite the latest experimental developments offer consistent methods to bridge a molecule between two electrodes (source and drain in a transistor notation), placing a third electrode (gate) close to the single-molecule electrical contact is still technically challenging. In this vein, electrochemically-gated single-molecule devices have emerged as an experimentally affordable alternative to overcome these technical limitations. In this review, the operating principle of an electrochemically-gated single-molecule device is presented together with the latest experimental methodologies to built them and characterize their charge transport characteristics. Then, an up-to-date comprehensive overview of the most prominent examples will be given, emphasizing on the relationship between the molecular structure and the final device electrical behaviour

Nano-manipulation of single DNA molecules

International Nuclear Information System (INIS)

Hu Jun; Shanghai Jiaotong Univ., Shanghai; Lv Junhong; Wang Guohua; Wang Ying; Li Minqian; Zhang Yi; Li Bin; Li Haikuo; An Hongjie

2004-01-01

Nano-manipulation of single atoms and molecules is a critical technique in nanoscience and nanotechnology. This review paper will focus on the recent development of the manipulation of single DNA molecules based on atomic force microscopy (AFM). Precise manipulation has been realized including varied manipulating modes such as 'cutting', 'pushing', 'folding', 'kneading', 'picking up', 'dipping', etc. The cutting accuracy is dominated by the size of the AFM tip, which is usually 10 nm or less. Single DNA fragments can be cut and picked up and then amplified by single molecule PCR. Thus positioning isolation and sequencing can be performed. (authors)

Absolute beam-charge measurement for single-bunch electron beams

International Nuclear Information System (INIS)

Suwada, Tsuyoshi; Ohsawa, Satoshi; Furukawa, Kazuro; Akasaka, Nobumasa

2000-01-01

The absolute beam charge of a single-bunch electron beam with a pulse width of 10 ps and that of a short-pulsed electron beam with a pulse width of 1 ns were measured with a Faraday cup in a beam test for the KEK B-Factory (KEKB) injector linac. It is strongly desired to obtain a precise beam-injection rate to the KEKB rings, and to estimate the amount of beam loss. A wall-current monitor was also recalibrated within an error of ±2%. This report describes the new results for an absolute beam-charge measurement for single-bunch and short-pulsed electron beams, and recalibration of the wall-current monitors in detail. (author)

Single Molecule Spectroscopy of Electron Transfer

International Nuclear Information System (INIS)

Holman, Michael; Zang, Ling; Liu, Ruchuan; Adams, David M.

2009-01-01

The objectives of this research are threefold: (1) to develop methods for the study electron transfer processes at the single molecule level, (2) to develop a series of modifiable and structurally well defined molecular and nanoparticle systems suitable for detailed single molecule/particle and bulk spectroscopic investigation, (3) to relate experiment to theory in order to elucidate the dependence of electron transfer processes on molecular and electronic structure, coupling and reorganization energies. We have begun the systematic development of single molecule spectroscopy (SMS) of electron transfer and summaries of recent studies are shown. There is a tremendous need for experiments designed to probe the discrete electronic and molecular dynamic fluctuations of single molecules near electrodes and at nanoparticle surfaces. Single molecule spectroscopy (SMS) has emerged as a powerful method to measure properties of individual molecules which would normally be obscured in ensemble-averaged measurement. Fluctuations in the fluorescence time trajectories contain detailed molecular level statistical and dynamical information of the system. The full distribution of a molecular property is revealed in the stochastic fluctuations, giving information about the range of possible behaviors that lead to the ensemble average. In the case of electron transfer, this level of understanding is particularly important to the field of molecular and nanoscale electronics: from a device-design standpoint, understanding and controlling this picture of the overall range of possible behaviors will likely prove to be as important as designing ia the ideal behavior of any given molecule.

Fast recognition of single molecules based on single-event photon statistics

International Nuclear Information System (INIS)

Dong Shuangli; Huang Tao; Liu Yuan; Wang Jun; Zhang Guofeng; Xiao Liantuan; Jia Suotang

2007-01-01

Mandel's Q parameter, which is determined from single-event photon statistics, provides an alternative way to recognize single molecules with fluorescence detection, other than the second-order correlation function. It is shown that the Q parameter of an assumed ideal double-molecule fluorescence with the same average photon number as that of the sample fluorescence can act as the criterion for single-molecule recognition. The influence of signal-to-background ratio and the error estimates for photon statistics are also presented. We have applied this method to ascertain single Cy5 dye molecules within hundreds of milliseconds

A Brief Introduction to Single-Molecule Fluorescence Methods.

Science.gov (United States)

van den Wildenberg, Siet M J L; Prevo, Bram; Peterman, Erwin J G

2018-01-01

One of the more popular single-molecule approaches in biological science is single-molecule fluorescence microscopy, which will be the subject of the following section of this volume. Fluorescence methods provide the sensitivity required to study biology on the single-molecule level, but they also allow access to useful measurable parameters on time and length scales relevant for the biomolecular world. Before several detailed experimental approaches will be addressed, we will first give a general overview of single-molecule fluorescence microscopy. We start with discussing the phenomenon of fluorescence in general and the history of single-molecule fluorescence microscopy. Next, we will review fluorescent probes in more detail and the equipment required to visualize them on the single-molecule level. We will end with a description of parameters measurable with such approaches, ranging from protein counting and tracking, single-molecule localization super-resolution microscopy, to distance measurements with Förster Resonance Energy Transfer and orientation measurements with fluorescence polarization.

Single-Molecule Analysis of Pre-mRNA Splicing with Colocalization Single-Molecule Spectroscopy (CoSMoS).

Science.gov (United States)

Braun, Joerg E; Serebrov, Victor

2017-01-01

Recent development of single-molecule techniques to study pre-mRNA splicing has provided insights into the dynamic nature of the spliceosome. Colocalization single-molecule spectroscopy (CoSMoS) allows following spliceosome assembly in real time at single-molecule resolution in the full complexity of cellular extracts. A detailed protocol of CoSMoS has been published previously (Anderson and Hoskins, Methods Mol Biol 1126:217-241, 2014). Here, we provide an update on the technical advances since the first CoSMoS studies including slide surface treatment, data processing, and representation. We describe various labeling strategies to generate RNA reporters with multiple dyes (or other moieties) at specific locations.

Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape.

Science.gov (United States)

Ferreon, Allan Chris M; Moosa, Mahdi Muhammad; Gambin, Yann; Deniz, Ashok A

2012-10-30

Protein structure and function depend on a close interplay between intrinsic folding energy landscapes and the chemistry of the protein environment. Osmolytes are small-molecule compounds that can act as chemical chaperones by altering the environment in a cellular context. Despite their importance, detailed studies on the role of these chemical chaperones in modulating structure and dimensions of intrinsically disordered proteins have been limited. Here, we used single-molecule Förster resonance energy transfer to test the counteraction hypothesis of counterbalancing effects between the protecting osmolyte trimethylamine-N-oxide (TMAO) and denaturing osmolyte urea for the case of α-synuclein, a Parkinson's disease-linked protein whose monomer exhibits significant disorder. The single-molecule experiments, which avoid complications from protein aggregation, do not exhibit clear solvent-induced cooperative protein transitions for these osmolytes, unlike results from previous studies on globular proteins. Our data demonstrate the ability of TMAO and urea to shift α-synuclein structures towards either more compact or expanded average dimensions. Strikingly, the experiments directly reveal that a 21 [urea][TMAO] ratio has a net neutral effect on the protein's dimensions, a result that holds regardless of the absolute osmolyte concentrations. Our findings shed light on a surprisingly simple aspect of the interplay between urea and TMAO on α-synuclein in the context of intrinsically disordered proteins, with potential implications for the biological roles of such chemical chaperones. The results also highlight the strengths of single-molecule experiments in directly probing the chemical physics of protein structure and disorder in more chemically complex environments.

Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape

Science.gov (United States)

Ferreon, Allan Chris M.; Moosa, Mahdi Muhammad; Deniz, Ashok A.

2012-01-01

Protein structure and function depend on a close interplay between intrinsic folding energy landscapes and the chemistry of the protein environment. Osmolytes are small-molecule compounds that can act as chemical chaperones by altering the environment in a cellular context. Despite their importance, detailed studies on the role of these chemical chaperones in modulating structure and dimensions of intrinsically disordered proteins have been limited. Here, we used single-molecule Förster resonance energy transfer to test the counteraction hypothesis of counterbalancing effects between the protecting osmolyte trimethylamine-N-oxide (TMAO) and denaturing osmolyte urea for the case of α-synuclein, a Parkinson’s disease-linked protein whose monomer exhibits significant disorder. The single-molecule experiments, which avoid complications from protein aggregation, do not exhibit clear solvent-induced cooperative protein transitions for these osmolytes, unlike results from previous studies on globular proteins. Our data demonstrate the ability of TMAO and urea to shift α-synuclein structures towards either more compact or expanded average dimensions. Strikingly, the experiments directly reveal that a 2∶1 [urea]∶[TMAO] ratio has a net neutral effect on the protein’s dimensions, a result that holds regardless of the absolute osmolyte concentrations. Our findings shed light on a surprisingly simple aspect of the interplay between urea and TMAO on α-synuclein in the context of intrinsically disordered proteins, with potential implications for the biological roles of such chemical chaperones. The results also highlight the strengths of single-molecule experiments in directly probing the chemical physics of protein structure and disorder in more chemically complex environments. PMID:22826265

The consequences of translational and rotational entropy lost by small molecules on binding to proteins

Science.gov (United States)

Murray, Christopher W.; Verdonk, Marcel L.

2002-10-01

When a small molecule binds to a protein, it loses a significant amount of rigid body translational and rotational entropy. Estimates of the associated energy barrier vary widely in the literature yet accurate estimates are important in the interpretation of results from fragment-based drug discovery techniques. This paper describes an analysis that allows the estimation of the rigid body entropy barrier from the increase in binding affinities that results when two fragments of known affinity and known binding mode are joined together. The paper reviews the relatively rare number of examples where good quality data is available. From the analysis of this data, we estimate that the barrier to binding, due to the loss of rigid-body entropy, is 15-20 kJ/mol, i.e. around 3 orders of magnitude in affinity at 298 K. This large barrier explains why it is comparatively rare to observe multiple fragments binding to non-overlapping adjacent sites in enzymes. The barrier is also consistent with medicinal chemistry experience where small changes in the critical binding regions of ligands are often poorly tolerated by enzymes.

Relation Entropy and Transferable Entropy Think of Aggregation on Group Decision Making

Institute of Scientific and Technical Information of China (English)

CHENG Qi-yue; QIU Wan-hua; LIU Xiao-feng

2002-01-01

In this paper, aggregation question based on group decision making and a single decision making is studied. The theory of entropy is applied to the sets pair analysis. The system of relation entropy and the transferable entropy notion are put. The character is studied. An potential by the relation entropy and transferable entropy are defined. It is the consistency measure on the group between a single decision making. We gained a new aggregation effective definition on the group misjudge.

Twinning of Polymer Crystals Suppressed by Entropy

Directory of Open Access Journals (Sweden)

Nikos Ch. Karayiannis

2014-09-01

Full Text Available We propose an entropic argument as partial explanation of the observed scarcity of twinned structures in crystalline samples of synthetic organic polymeric materials. Polymeric molecules possess a much larger number of conformational degrees of freedom than low molecular weight substances. The preferred conformations of polymer chains in the bulk of a single crystal are often incompatible with the conformations imposed by the symmetry of a growth twin, both at the composition surfaces and in the twin axis. We calculate the differences in conformational entropy between chains in single crystals and chains in twinned crystals, and find that the reduction in chain conformational entropy in the twin is sufficient to make the single crystal the stable thermodynamic phase. The formation of cyclic twins in molecular dynamics simulations of chains of hard spheres must thus be attributed to kinetic factors. In more realistic polymers this entropic contribution to the free energy can be canceled or dominated by nonbonded and torsional energetics.

A brief introduction to single-molecule fluorescence methods

NARCIS (Netherlands)

Wildenberg, S.M.J.L.; Prevo, B.; Peterman, E.J.G.; Peterman, EJG; Wuite, GJL

2011-01-01

One of the more popular single-molecule approaches in biological science is single-molecule fluorescence microscopy, which is the subject of the following section of this volume. Fluorescence methods provide the sensitivity required to study biology on the single-molecule level, but they also allow

A brief introduction to single-molecule fluorescence methods

NARCIS (Netherlands)

van den Wildenberg, Siet M.J.L.; Prevo, Bram; Peterman, Erwin J.G.

2018-01-01

One of the more popular single-molecule approaches in biological science is single-molecule fluorescence microscopy, which will be the subject of the following section of this volume. Fluorescence methods provide the sensitivity required to study biology on the single-molecule level, but they also

Single-molecule techniques in biophysics: a review of the progress in methods and applications

Science.gov (United States)

Miller, Helen; Zhou, Zhaokun; Shepherd, Jack; Wollman, Adam J. M.; Leake, Mark C.

2018-02-01

Single-molecule biophysics has transformed our understanding of biology, but also of the physics of life. More exotic than simple soft matter, biomatter lives far from thermal equilibrium, covering multiple lengths from the nanoscale of single molecules to up to several orders of magnitude higher in cells, tissues and organisms. Biomolecules are often characterized by underlying instability: multiple metastable free energy states exist, separated by levels of just a few multiples of the thermal energy scale k B T, where k B is the Boltzmann constant and T absolute temperature, implying complex inter-conversion kinetics in the relatively hot, wet environment of active biological matter. A key benefit of single-molecule biophysics techniques is their ability to probe heterogeneity of free energy states across a molecular population, too challenging in general for conventional ensemble average approaches. Parallel developments in experimental and computational techniques have catalysed the birth of multiplexed, correlative techniques to tackle previously intractable biological questions. Experimentally, progress has been driven by improvements in sensitivity and speed of detectors, and the stability and efficiency of light sources, probes and microfluidics. We discuss the motivation and requirements for these recent experiments, including the underpinning mathematics. These methods are broadly divided into tools which detect molecules and those which manipulate them. For the former we discuss the progress of super-resolution microscopy, transformative for addressing many longstanding questions in the life sciences, and for the latter we include progress in ‘force spectroscopy’ techniques that mechanically perturb molecules. We also consider in silico progress of single-molecule computational physics, and how simulation and experimentation may be drawn together to give a more complete understanding. Increasingly, combinatorial techniques are now used, including

Direct single-molecule dynamic detection of chemical reactions.

Science.gov (United States)

Guan, Jianxin; Jia, Chuancheng; Li, Yanwei; Liu, Zitong; Wang, Jinying; Yang, Zhongyue; Gu, Chunhui; Su, Dingkai; Houk, Kendall N; Zhang, Deqing; Guo, Xuefeng

2018-02-01

Single-molecule detection can reveal time trajectories and reaction pathways of individual intermediates/transition states in chemical reactions and biological processes, which is of fundamental importance to elucidate their intrinsic mechanisms. We present a reliable, label-free single-molecule approach that allows us to directly explore the dynamic process of basic chemical reactions at the single-event level by using stable graphene-molecule single-molecule junctions. These junctions are constructed by covalently connecting a single molecule with a 9-fluorenone center to nanogapped graphene electrodes. For the first time, real-time single-molecule electrical measurements unambiguously show reproducible large-amplitude two-level fluctuations that are highly dependent on solvent environments in a nucleophilic addition reaction of hydroxylamine to a carbonyl group. Both theoretical simulations and ensemble experiments prove that this observation originates from the reversible transition between the reactant and a new intermediate state within a time scale of a few microseconds. These investigations open up a new route that is able to be immediately applied to probe fast single-molecule physics or biophysics with high time resolution, making an important contribution to broad fields beyond reaction chemistry.

Single Molecule Nanoelectrochemistry in Electrical Junctions.

Science.gov (United States)

Nichols, Richard J; Higgins, Simon J

2016-11-15

It is now possible to reliably measure single molecule conductance in a wide variety of environments including organic liquids, ultrahigh vacuum, water, ionic liquids, and electrolytes. The most commonly used methods deploy scanning probe microscopes, mechanically formed break junctions, or lithographically formed nanogap contacts. Molecules are generally captured between a pair of facing electrodes, and the junction current response is measured as a function of bias voltage. Gating electrodes can also be added so that the electrostatic potential at the molecular bridge can be independently controlled by this third noncontacting electrode. This can also be achieved in an electrolytic environment using a four-electrode bipotentiostatic configuration, which allows independent electrode potential control of the two contacting electrodes. This is commonly realized using an electrochemical STM and enables single molecule electrical characterization as a function of electrode potential and redox state of the molecular bridge. This has emerged as a powerful tool in modern interfacial electrochemistry and nanoelectrochemistry for studying charge transport across single molecules as a function of electrode potential and the electrolytic environments. Such measurements are possible in electrolytes ranging from aqueous buffers to nonaqueous ionic liquids. In this Account, we illustrate a number of examples of single molecule electrical measurements under electrode potential control use a scanning tunneling microscope (STM) and demonstrate how these can help in the understanding of charge transport in single molecule junctions. Examples showing charge transport following phase coherent tunneling to incoherent charge hopping across redox active molecular bridges are shown. In the case of bipyridinium (or viologen) molecular wires, it is shown how electrochemical reduction leads to an increase of the single molecule conductance, which is controlled by the liquid electrochemical

Challenges for single molecule electronic devices with nanographene and organic molecules. Do single molecules offer potential as elements of electronic devices in the next generation?

Science.gov (United States)

Enoki, Toshiaki; Kiguchi, Manabu

2018-03-01

Interest in utilizing organic molecules to fabricate electronic materials has existed ever since organic (molecular) semiconductors were first discovered in the 1950s. Since then, scientists have devoted serious effort to the creation of various molecule-based electronic systems, such as molecular metals and molecular superconductors. Single-molecule electronics and the associated basic science have emerged over the past two decades and provided hope for the development of highly integrated molecule-based electronic devices in the future (after the Si-based technology era has ended). Here, nanographenes (nano-sized graphene) with atomically precise structures are among the most promising molecules that can be utilized for electronic/spintronic devices. To manipulate single small molecules for an electronic device, a single molecular junction has been developed. It is a powerful tool that allows even small molecules to be utilized. External electric, magnetic, chemical, and mechanical perturbations can change the physical and chemical properties of molecules in a way that is different from bulk materials. Therefore, the various functionalities of molecules, along with changes induced by external perturbations, allows us to create electronic devices that we cannot create using current top-down Si-based technology. Future challenges that involve the incorporation of condensed matter physics, quantum chemistry calculations, organic synthetic chemistry, and electronic device engineering are expected to open a new era in single-molecule device electronic technology.

Single-Molecule Electronics: Chemical and Analytical Perspectives.

Science.gov (United States)

Nichols, Richard J; Higgins, Simon J

2015-01-01

It is now possible to measure the electrical properties of single molecules using a variety of techniques including scanning probe microcopies and mechanically controlled break junctions. Such measurements can be made across a wide range of environments including ambient conditions, organic liquids, ionic liquids, aqueous solutions, electrolytes, and ultra high vacuum. This has given new insights into charge transport across molecule electrical junctions, and these experimental methods have been complemented with increasingly sophisticated theory. This article reviews progress in single-molecule electronics from a chemical perspective and discusses topics such as the molecule-surface coupling in electrical junctions, chemical control, and supramolecular interactions in junctions and gating charge transport. The article concludes with an outlook regarding chemical analysis based on single-molecule conductance.

Single Molecule Biophysics Experiments and Theory

CERN Document Server

Komatsuzaki, Tamiki; Takahashi, Satoshi; Yang, Haw; Silbey, Robert J; Rice, Stuart A; Dinner, Aaron R

2011-01-01

Discover the experimental and theoretical developments in optical single-molecule spectroscopy that are changing the ways we think about molecules and atoms The Advances in Chemical Physics series provides the chemical physics field with a forum for critical, authoritative evaluations of advances in every area of the discipline. This latest volume explores the advent of optical single-molecule spectroscopy, and how atomic force microscopy has empowered novel experiments on individual biomolecules, opening up new frontiers in molecular and cell biology and leading to new theoretical approaches

Single molecule detection, thermal fluctuation and life

Science.gov (United States)

YANAGIDA, Toshio; ISHII, Yoshiharu

2017-01-01

Single molecule detection has contributed to our understanding of the unique mechanisms of life. Unlike artificial man-made machines, biological molecular machines integrate thermal noises rather than avoid them. For example, single molecule detection has demonstrated that myosin motors undergo biased Brownian motion for stepwise movement and that single protein molecules spontaneously change their conformation, for switching to interactions with other proteins, in response to thermal fluctuation. Thus, molecular machines have flexibility and efficiency not seen in artificial machines. PMID:28190869

On theory of single-molecule transistor

International Nuclear Information System (INIS)

Tran Tien Phuc

2009-01-01

The results of the study on single-molecule transistor are mainly investigated in this paper. The structure of constructed single-molecule transistor is similar to a conventional MOSFET. The conductive channel of the transistors is a single-molecule of halogenated benzene derivatives. The chemical simulation software CAChe was used to design and implement for the essential parameter of the molecules utilized as the conductive channel. The GUI of Matlab has been built to design its graphical interface, calculate and plot the output I-V characteristic curves for the transistor. The influence of temperature, length and width of the conductive channel, and gate voltage is considered. As a result, the simulated curves are similar to the traditional MOSFET's. The operating temperature range of the transistors is wider compared with silicon semiconductors. The supply voltage for transistors is only about 1 V. The size of transistors in this research is several nanometers.

Molecular electronics: the single molecule switch and transistor

NARCIS (Netherlands)

Sotthewes, Kai; Geskin, Victor; Heimbuch, Rene; Kumar, Avijit; Zandvliet, Henricus J.W.

2014-01-01

In order to design and realize single-molecule devices it is essential to have a good understanding of the properties of an individual molecule. For electronic applications, the most important property of a molecule is its conductance. Here we show how a single octanethiol molecule can be connected

Single-Molecule Plasmon Sensing: Current Status and Future Prospects.

Science.gov (United States)

Taylor, Adam B; Zijlstra, Peter

2017-08-25

Single-molecule detection has long relied on fluorescent labeling with high quantum-yield fluorophores. Plasmon-enhanced detection circumvents the need for labeling by allowing direct optical detection of weakly emitting and completely nonfluorescent species. This review focuses on recent advances in single molecule detection using plasmonic metal nanostructures as a sensing platform, particularly using a single particle-single molecule approach. In the past decade two mechanisms for plasmon-enhanced single-molecule detection have been demonstrated: (1) by plasmonically enhancing the emission of weakly fluorescent biomolecules, or (2) by monitoring shifts of the plasmon resonance induced by single-molecule interactions. We begin with a motivation regarding the importance of single molecule detection, and advantages plasmonic detection offers. We describe both detection mechanisms and discuss challenges and potential solutions. We finalize by highlighting the exciting possibilities in analytical chemistry and medical diagnostics.

Observing single molecule chemical reactions on metal nanoparticles.

Energy Technology Data Exchange (ETDEWEB)

Emory, S. R. (Steven R.); Ambrose, W. Patrick; Goodwin, P. M. (Peter M); Keller, Richard A.

2001-01-01

We report the study of the photodecomposition of single Rhodamine 6G (R6G) dye molecules adsorbed on silver nanoparticles. The nanoparticles were immobilized and spatially isolated on polylysine-derivatized glass coverslips, and confocal laser microspectroscopy was used to obtain surface-enhanced Raman scattering (SERS) spectra from individual R6G molecules. The photodecomposition of these molecules was observed with 150-ms temporal resolution. The photoproduct was identified as graphitic carbon based on the appearance of broad SERS vibrational bands at 1592 cm{sup -1} and 1340 cm{sup -1} observed in both bulk and averaged single-molecule photoproduct spectra. In contrast, when observed at the single-molecule level, the photoproduct yielded sharp SERS spectra. The inhomogeneous broadening of the bulk SERS spectra is due to a variety of photoproducts in different surface orientations and is a characteristic of ensemble-averaged measurements of disordered systems. These single-molecule studies indicate a photodecomposition pathway by which the R6G molecule desorbs from the metal surface, an excited-state photoreaction occurs, and the R6G photoproduct(s) readsorbs to the surface. A SERS spectrum is obtained when either the intact R6G or the R6G photoproduct(s) are adsorbed on a SERS-active site. This work further illustrates the power of single-molecule spectroscopy (SMS) to reveal unique behaviors of single molecules that are not discernable with bulk measurements.

Single-Molecule Transport at a Rectifying GaAs Contact.

Science.gov (United States)

Vezzoli, Andrea; Brooke, Richard J; Ferri, Nicolò; Higgins, Simon J; Schwarzacher, Walther; Nichols, Richard J

2017-02-08

In most single- or few-molecule devices, the contact electrodes are simple ohmic resistors. Here we describe a new type of single-molecule device in which metal and semiconductor contact electrodes impart a function, namely, current rectification, which is then modified by a molecule bridging the gap. We study junctions with the structure Au STM tip/X/n-GaAs substrate, where "X" is either a simple alkanedithiol or a conjugated unit bearing thiol/methylthiol contacts, and we detect current jumps corresponding to the attachment and detachment of single molecules. From the magnitudes of the current jumps we can deduce values for the conductance decay constant with molecule length that agree well with values determined from Au/molecule/Au junctions. The ability to impart functionality to a single-molecule device through the properties of the contacts as well as through the properties of the molecule represents a significant extension of the single-molecule electronics "tool-box".

Single molecule force spectroscopy: methods and applications in biology

International Nuclear Information System (INIS)

Shen Yi; Hu Jun

2012-01-01

Single molecule measurements have transformed our view of biomolecules. Owing to the ability of monitoring the activity of individual molecules, we now see them as uniquely structured, fluctuating molecules that stochastically transition between frequently many substrates, as two molecules do not follow precisely the same trajectory. Indeed, it is this discovery of critical yet short-lived substrates that were often missed in ensemble measurements that has perhaps contributed most to the better understanding of biomolecular functioning resulting from single molecule experiments. In this paper, we give a review on the three major techniques of single molecule force spectroscopy, and their applications especially in biology. The single molecular study of biotin-streptavidin interactions is introduced as a successful example. The problems and prospects of the single molecule force spectroscopy are discussed, too. (authors)

Investigating single molecule adhesion by atomic force spectroscopy.

Science.gov (United States)

Stetter, Frank W S; Kienle, Sandra; Krysiak, Stefanie; Hugel, Thorsten

2015-02-27

Atomic force spectroscopy is an ideal tool to study molecules at surfaces and interfaces. An experimental protocol to couple a large variety of single molecules covalently onto an AFM tip is presented. At the same time the AFM tip is passivated to prevent unspecific interactions between the tip and the substrate, which is a prerequisite to study single molecules attached to the AFM tip. Analyses to determine the adhesion force, the adhesion length, and the free energy of these molecules on solid surfaces and bio-interfaces are shortly presented and external references for further reading are provided. Example molecules are the poly(amino acid) polytyrosine, the graft polymer PI-g-PS and the phospholipid POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine). These molecules are desorbed from different surfaces like CH3-SAMs, hydrogen terminated diamond and supported lipid bilayers under various solvent conditions. Finally, the advantages of force spectroscopic single molecule experiments are discussed including means to decide if truly a single molecule has been studied in the experiment.

Computer systems for annotation of single molecule fragments

Science.gov (United States)

Schwartz, David Charles; Severin, Jessica

2016-07-19

There are provided computer systems for visualizing and annotating single molecule images. Annotation systems in accordance with this disclosure allow a user to mark and annotate single molecules of interest and their restriction enzyme cut sites thereby determining the restriction fragments of single nucleic acid molecules. The markings and annotations may be automatically generated by the system in certain embodiments and they may be overlaid translucently onto the single molecule images. An image caching system may be implemented in the computer annotation systems to reduce image processing time. The annotation systems include one or more connectors connecting to one or more databases capable of storing single molecule data as well as other biomedical data. Such diverse array of data can be retrieved and used to validate the markings and annotations. The annotation systems may be implemented and deployed over a computer network. They may be ergonomically optimized to facilitate user interactions.

Massively Parallel Single-Molecule Manipulation Using Centrifugal Force

Science.gov (United States)

Wong, Wesley; Halvorsen, Ken

2011-03-01

Precise manipulation of single molecules has led to remarkable insights in physics, chemistry, biology, and medicine. However, two issues that have impeded the widespread adoption of these techniques are equipment cost and the laborious nature of making measurements one molecule at a time. To meet these challenges, we have developed an approach that enables massively parallel single- molecule force measurements using centrifugal force. This approach is realized in the centrifuge force microscope, an instrument in which objects in an orbiting sample are subjected to a calibration-free, macroscopically uniform force- field while their micro-to-nanoscopic motions are observed. We demonstrate high- throughput single-molecule force spectroscopy with this technique by performing thousands of rupture experiments in parallel, characterizing force-dependent unbinding kinetics of an antibody-antigen pair in minutes rather than days. Currently, we are taking steps to integrate high-resolution detection, fluorescence, temperature control and a greater dynamic range in force. With significant benefits in efficiency, cost, simplicity, and versatility, single-molecule centrifugation has the potential to expand single-molecule experimentation to a wider range of researchers and experimental systems.

Single molecule transcription profiling with AFM

International Nuclear Information System (INIS)

Reed, Jason; Mishra, Bud; Pittenger, Bede; Magonov, Sergei; Troke, Joshua; Teitell, Michael A; Gimzewski, James K

2007-01-01

Established techniques for global gene expression profiling, such as microarrays, face fundamental sensitivity constraints. Due to greatly increasing interest in examining minute samples from micro-dissected tissues, including single cells, unorthodox approaches, including molecular nanotechnologies, are being explored in this application. Here, we examine the use of single molecule, ordered restriction mapping, combined with AFM, to measure gene transcription levels from very low abundance samples. We frame the problem mathematically, using coding theory, and present an analysis of the critical error sources that may serve as a guide to designing future studies. We follow with experiments detailing the construction of high density, single molecule, ordered restriction maps from plasmids and from cDNA molecules, using two different enzymes, a result not previously reported. We discuss these results in the context of our calculations

Optical probing of single fluorescent molecules and proteins

NARCIS (Netherlands)

Garcia Parajo, M.F.; Veerman, J.A.; Bouwhuis, R.; Bouwhuis, Rudo; van Hulst, N.F.; Vallée, R.A.L.

2001-01-01

Single-molecule detection and analysis of organic fluorescent molecules and proteins are presented, with emphasis o­n the underlying principles methodology and the application of single-molecule analysis at room temperature. This Minireview is mainly focused o­n the application of confocal and

Theoretical Investigations Regarding Single Molecules

DEFF Research Database (Denmark)

Pedersen, Kim Georg Lind

Neoclassical Valence Bond Theory, Quantum Transport, Quantum Interference, Kondo Effect, and Electron Pumping. Trap a single organic molecule between two electrodes and apply a bias voltage across this "molecular junction". When electrons pass through the molecule, the different electron paths can...... interfere destructively or constructively. Destructive interference effects in electron transport could potentially improve thermo-electrics, organic logic circuits and energy harvesting. We have investigated destructive interference in off-resonant transport through organic molecules, and have found a set...

Single Molecule Nano-Metronome

OpenAIRE

Buranachai, Chittanon; McKinney, Sean A.; Ha, Taekjip

2006-01-01

We constructed a DNA-based nano-mechanical device called the nano-metronome. Our device is made by introducing complementary single stranded overhangs at the two arms of the DNA four-way junction. The ticking rates of this stochastic metronome depend on ion concentrations and can be changed by a set of DNA-based switches to deactivate/reactivate the sticky end. Since the device displays clearly distinguishable responses even with a single basepair difference, it may lead to a single molecule ...

Investigation on Single-Molecule Junctions Based on Current–Voltage Characteristics

Directory of Open Access Journals (Sweden)

Yuji Isshiki

2018-02-01

Full Text Available The relationship between the current through an electronic device and the voltage across its terminals is a current–voltage characteristic (I–V that determine basic device performance. Currently, I–V measurement on a single-molecule scale can be performed using break junction technique, where a single molecule junction can be prepared by trapping a single molecule into a nanogap between metal electrodes. The single-molecule I–Vs provide not only the device performance, but also reflect information on energy dispersion of the electronic state and the electron-molecular vibration coupling in the junction. This mini review focuses on recent representative studies on I–Vs of the single molecule junctions that cover investigation on the single-molecule diode property, the molecular vibration, and the electronic structure as a form of transmission probability, and electronic density of states, including the spin state of the single-molecule junctions. In addition, thermoelectronic measurements based on I–Vs and identification of the charged carriers (i.e., electrons or holes are presented. The analysis in the single-molecule I–Vs provides fundamental and essential information for a better understanding of the single-molecule science, and puts the single molecule junction to more practical use in molecular devices.

Novel approaches for single molecule activation and detection

CERN Document Server

Benfenati, Fabio; Torre, Vincent

2014-01-01

How can we obtain tools able to process and exchange information at the molecular scale In order to do this, it is necessary to activate and detect single molecules under controlled conditions. This book focuses on the generation of biologically-inspired molecular devices. These devices are based on the developments of new photonic tools able to activate and stimulate single molecule machines. Additionally, new light sensitive molecules can be selectively activated by photonic tools. These technological innovations will provide a way to control activation of single light-sensitive molecules, a

Calculation of Five Thermodynamic Molecular Descriptors by Means of a General Computer Algorithm Based on the Group-Additivity Method: Standard Enthalpies of Vaporization, Sublimation and Solvation, and Entropy of Fusion of Ordinary Organic Molecules and Total Phase-Change Entropy of Liquid Crystals

Directory of Open Access Journals (Sweden)

Rudolf Naef

2017-06-01

Full Text Available The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion as well as the total phase-change entropy of liquid crystals. The present method is based on the complete breakdown of the molecules into their constituting atoms and their immediate neighbourhood; the respective calculations of the contribution of the atomic groups by means of the Gauss-Seidel fitting method is based on experimental data collected from literature. The feasibility of the calculations for each of the mentioned descriptors was verified by means of a 10-fold cross-validation procedure proving the good to high quality of the predicted values for the three mentioned enthalpies and for the entropy of fusion, whereas the predictive quality for the total phase-change entropy of liquid crystals was poor. The goodness of fit (Q2 and the standard deviation (σ of the cross-validation calculations for the five descriptors was as follows: 0.9641 and 4.56 kJ/mol (N = 3386 test molecules for the enthalpy of vaporization, 0.8657 and 11.39 kJ/mol (N = 1791 for the enthalpy of sublimation, 0.9546 and 4.34 kJ/mol (N = 373 for the enthalpy of solvation, 0.8727 and 17.93 J/mol/K (N = 2637 for the entropy of fusion and 0.5804 and 32.79 J/mol/K (N = 2643 for the total phase-change entropy of liquid crystals. The large discrepancy between the results of the two closely related entropies is discussed in detail. Molecules for which both the standard enthalpies of vaporization and sublimation were calculable, enabled the estimation of their standard enthalpy of fusion by simple subtraction of the former from the latter enthalpy. For 990 of them the experimental enthalpy-of-fusion values are also known, allowing their comparison with predictions, yielding a correlation

Calculation of Five Thermodynamic Molecular Descriptors by Means of a General Computer Algorithm Based on the Group-Additivity Method: Standard Enthalpies of Vaporization, Sublimation and Solvation, and Entropy of Fusion of Ordinary Organic Molecules and Total Phase-Change Entropy of Liquid Crystals.

Science.gov (United States)

Naef, Rudolf; Acree, William E

2017-06-25

The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion as well as the total phase-change entropy of liquid crystals. The present method is based on the complete breakdown of the molecules into their constituting atoms and their immediate neighbourhood; the respective calculations of the contribution of the atomic groups by means of the Gauss-Seidel fitting method is based on experimental data collected from literature. The feasibility of the calculations for each of the mentioned descriptors was verified by means of a 10-fold cross-validation procedure proving the good to high quality of the predicted values for the three mentioned enthalpies and for the entropy of fusion, whereas the predictive quality for the total phase-change entropy of liquid crystals was poor. The goodness of fit ( Q ²) and the standard deviation (σ) of the cross-validation calculations for the five descriptors was as follows: 0.9641 and 4.56 kJ/mol ( N = 3386 test molecules) for the enthalpy of vaporization, 0.8657 and 11.39 kJ/mol ( N = 1791) for the enthalpy of sublimation, 0.9546 and 4.34 kJ/mol ( N = 373) for the enthalpy of solvation, 0.8727 and 17.93 J/mol/K ( N = 2637) for the entropy of fusion and 0.5804 and 32.79 J/mol/K ( N = 2643) for the total phase-change entropy of liquid crystals. The large discrepancy between the results of the two closely related entropies is discussed in detail. Molecules for which both the standard enthalpies of vaporization and sublimation were calculable, enabled the estimation of their standard enthalpy of fusion by simple subtraction of the former from the latter enthalpy. For 990 of them the experimental enthalpy-of-fusion values are also known, allowing their comparison with predictions, yielding a correlation coefficient R

Spectroscopic characterization of Venus at the single molecule level.

Science.gov (United States)

David, Charlotte C; Dedecker, Peter; De Cremer, Gert; Verstraeten, Natalie; Kint, Cyrielle; Michiels, Jan; Hofkens, Johan

2012-02-01

Venus is a recently developed, fast maturating, yellow fluorescent protein that has been used as a probe for in vivo applications. In the present work the photophysical characteristics of Venus were analyzed spectroscopically at the bulk and single molecule level. Through time-resolved single molecule measurements we found that single molecules of Venus display pronounced fluctuations in fluorescence emission, with clear fluorescence on- and off-times. These fluorescence intermittencies were found to occupy a broad range of time scales, ranging from milliseconds to several seconds. Such long off-times can complicate the analysis of single molecule counting experiments or single-molecule FRET experiments. This journal is © The Royal Society of Chemistry and Owner Societies 2012

Single-base resolution and long-coverage sequencing based on single-molecule nanomanipulation

International Nuclear Information System (INIS)

An Hongjie; Huang Jiehuan; Lue Ming; Li Xueling; Lue Junhong; Li Haikuo; Zhang Yi; Li Minqian; Hu Jun

2007-01-01

We show new approaches towards a novel single-molecule sequencing strategy which consists of high-resolution positioning isolation of overlapping DNA fragments with atomic force microscopy (AFM), subsequent single-molecule PCR amplification and conventional Sanger sequencing. In this study, a DNA labelling technique was used to guarantee the accuracy in positioning the target DNA. Single-molecule multiplex PCR was carried out to test the contamination. The results showed that the two overlapping DNA fragments isolated by AFM could be successfully sequenced with high quality and perfect contiguity, indicating that single-base resolution and long-coverage sequencing have been achieved simultaneously

Lattice diffusion of a single molecule in solution

Science.gov (United States)

Ruggeri, Francesca; Krishnan, Madhavi

2017-12-01

The ability to trap a single molecule in an electrostatic potential well in solution has opened up new possibilities for the use of molecular electrical charge to study macromolecular conformation and dynamics at the level of the single entity. Here we study the diffusion of a single macromolecule in a two-dimensional lattice of electrostatic traps in solution. We report the ability to measure both the size and effective electrical charge of a macromolecule by observing single-molecule transport trajectories, typically a few seconds in length, using fluorescence microscopy. While, as shown previously, the time spent by the molecule in a trap is a strong function of its effective charge, we demonstrate here that the average travel time between traps in the landscape yields its hydrodynamic radius. Tailoring the pitch of the lattice thus yields two different experimentally measurable time scales that together uniquely determine both the size and charge of the molecule. Since no information is required on the location of the molecule between consecutive departure and arrival events at lattice sites, the technique is ideally suited to measurements on weakly emitting entities such as single molecules.

The origin of transverse anisotropy in axially symmetric single molecule magnets.

Science.gov (United States)

Barra, Anne-Laure; Caneschi, Andrea; Cornia, Andrea; Gatteschi, Dante; Gorini, Lapo; Heiniger, Leo-Philipp; Sessoli, Roberta; Sorace, Lorenzo

2007-09-05

Single-crystal high-frequency electron paramagnetic resonance spectroscopy has been employed on a truly axial single molecule magnet of formula [Mn(12)O(12)(tBu-CH(2)CO(2))16(CH(3)OH)4].CH(3)OH to investigate the origin of the transverse magnetic anisotropy, a crucial parameter that rules the quantum tunneling of the magnetization. The crystal structure, including the absolute structure of the crystal used for EPR experiments, has been fully determined and found to belong to I4 tetragonal space group. The angular dependence of the resonance fields in the crystallographic ab plane shows the presence of high-order tetragonal anisotropy and strong dependence on the MS sublevels with the second-highest-field transition being angular independent. This was rationalized including competing fourth- and sixth-order transverse parameters in a giant spin Hamiltonian which describes the magnetic anisotropy in the ground S = 10 spin state of the cluster. To establish the origin of these anisotropy terms, the experimental results have been further analyzed using a simplified multispin Hamiltonian which takes into account the exchange interactions and the single ion magnetic anisotropy of the Mn(III) centers. It has been possible to establish magnetostructural correlations with spin Hamiltonian parameters up to the sixth order. Transverse anisotropy in axial single molecule magnets was found to originate from the multispin nature of the system and from the breakdown of the strong exchange approximation. The tilting of the single-ion easy axes of magnetization with respect to the 4-fold molecular axis of the cluster plays the major role in determining the transverse anisotropy. Counterintuitively, the projections of the single ion easy axes on the ab plane correspond to hard axes of magnetization.

Extending Single-Molecule Microscopy Using Optical Fourier Processing

Science.gov (United States)

2015-01-01

This article surveys the recent application of optical Fourier processing to the long-established but still expanding field of single-molecule imaging and microscopy. A variety of single-molecule studies can benefit from the additional image information that can be obtained by modulating the Fourier, or pupil, plane of a widefield microscope. After briefly reviewing several current applications, we present a comprehensive and computationally efficient theoretical model for simulating single-molecule fluorescence as it propagates through an imaging system. Furthermore, we describe how phase/amplitude-modulating optics inserted in the imaging pathway may be modeled, especially at the Fourier plane. Finally, we discuss selected recent applications of Fourier processing methods to measure the orientation, depth, and rotational mobility of single fluorescent molecules. PMID:24745862

Single Molecule Nano-Metronome

Science.gov (United States)

Buranachai, Chittanon; McKinney, Sean A.; Ha, Taekjip

2008-01-01

We constructed a DNA-based nano-mechanical device called the nano-metronome. Our device is made by introducing complementary single stranded overhangs at the two arms of the DNA four-way junction. The ticking rates of this stochastic metronome depend on ion concentrations and can be changed by a set of DNA-based switches to deactivate/reactivate the sticky end. Since the device displays clearly distinguishable responses even with a single basepair difference, it may lead to a single molecule sensor of minute sequence differences of a target DNA. PMID:16522050

Controlling single-molecule junction conductance by molecular interactions

Science.gov (United States)

Kitaguchi, Y.; Habuka, S.; Okuyama, H.; Hatta, S.; Aruga, T.; Frederiksen, T.; Paulsson, M.; Ueba, H.

2015-01-01

For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment. PMID:26135251

DNA-psoralen interaction: a single molecule experiment.

Science.gov (United States)

Rocha, M S; Viana, N B; Mesquita, O N

2004-11-15

By attaching one end of a single lambda-DNA molecule to a microscope coverslip and the other end to a polystyrene microsphere trapped by an optical tweezers, we can study the entropic elasticity of the lambda-DNA by measuring force versus extension as we stretch the molecule. This powerful method permits single molecule studies. We are particularly interested in the effects of the photosensitive drug psoralen on the elasticity of the DNA molecule. We have illuminated the sample with different light sources, studying how the different wavelengths affect the psoralen-DNA linkage. To do this, we measure the persistence length of individual DNA-psoralen complexes.

Handbook of Single-Molecule Biophysics

CERN Document Server

Hinterdorfer, Peter

2009-01-01

The last decade has seen the development of a number of novel biophysical methods that allow the manipulation and study of individual biomolecules. The ability to monitor biological processes at this fundamental level of sensitivity has given rise to an improved understanding of the underlying molecular mechanisms. Through the removal of ensemble averaging, distributions and fluctuations of molecular properties can be characterized, transient intermediates identified, and catalytic mechanisms elucidated. By applying forces on biomolecules while monitoring their activity, important information can be obtained on how proteins couple function to structure. The Handbook of Single-Molecule Biophysics provides an introduction to these techniques and presents an extensive discussion of the new biological insights obtained from them. Coverage includes: Experimental techniques to monitor and manipulate individual biomolecules The use of single-molecule techniques in super-resolution and functional imaging Single-molec...

Quantum information entropies of ultracold atomic gases in a ...

Indian Academy of Sciences (India)

The position and momentum space information entropies of weakly interacting trapped atomic Bose–Einstein condensates and spin-polarized trapped atomic Fermi gases at absolute zero temperature are evaluated. We find that sum of the position and momentum space information entropies of these quantum systems ...

Zero-mode waveguide nanophotonic structures for single molecule characterization

Science.gov (United States)

Crouch, Garrison M.; Han, Donghoon; Bohn, Paul W.

2018-05-01

Single-molecule characterization has become a crucial research tool in the chemical and life sciences, but limitations, such as limited concentration range, inability to control molecular distributions in space, and intrinsic phenomena, such as photobleaching, present significant challenges. Recent developments in non-classical optics and nanophotonics offer promising routes to mitigating these restrictions, such that even low affinity (K D ~ mM) biomolecular interactions can be studied. Here we introduce and review specific nanophotonic devices used to support single molecule studies. Optical nanostructures, such as zero-mode waveguides (ZMWs), are usually fabricated in thin gold or aluminum films and serve to confine the observation volume of optical microspectroscopy to attoliter to zeptoliter volumes. These simple nanostructures allow individual molecules to be isolated for optical and electrochemical analysis, even when the molecules of interest are present at high concentration (µM–mM) in bulk solution. Arrays of ZMWs may be combined with optical probes such as single molecule fluorescence, single molecule fluorescence resonance energy transfer, and fluorescence correlation spectroscopy for distributed analysis of large numbers of single-molecule reactions or binding events in parallel. Furthermore, ZMWs may be used as multifunctional devices, for example by combining optical and electrochemical functions in a single discrete architecture to achieve electrochemical ZMWs. In this review, we will describe the optical properties, fabrication, and applications of ZMWs for single-molecule studies, as well as the integration of ZMWs into systems for chemical and biochemical analysis.

Thousand-fold enhancement of single-molecule fluorescence near a single gold nanorod

NARCIS (Netherlands)

Yuan, H.; Khatua, S.; Zijlstra, P.; Yorulmaz, M.; Orrit, M.

2013-01-01

Single molecules: Large enhancements of single-molecule fluorescence up to 1100 times by using synthesized gold nanorods are reported (see picture). This high enhancement is achieved by selecting a dye with its adsorption and emission close to the surface plasmon resonance of the gold nanorods

Single Molecule Conductance of Oligothiophene Derivatives

Science.gov (United States)

Dell, Emma J.

This thesis studies the electronic properties of small organic molecules based on the thiophene motif. If we are to build next-generation devices, advanced materials must be designed which possess requisite electronic functionality. Molecules present attractive candidates for these ad- vanced materials since nanoscale devices are particularly sought after. However, selecting a molecule that is suited to a certain electronic function remains a challenge, and characterization of electronic behavior is therefore critical. Single molecule conductance measurements are a powerful tool to determine properties on the nanoscale and, as such, can be used to investigate novel building blocks that may fulfill the design requirements of next-generation devices. Combining these conductance results with strategic chemical synthesis allows for the development of new families of molecules that show attractive properties for future electronic devices. Since thiophene rings are the fruitflies of organic semiconductors on the bulk scale, they present an intriguing starting point for building functional materials on the nanoscale, and therefore form the structural basis of all molecules studied herein. First, the single-molecule conductance of a family of bithiophene derivatives was measured. A broad distribution in the single-molecule conductance of bithiophene was found compared with that of a biphenyl. This increased breadth in the conductance distribution was shown to be explained by the difference in 5-fold symmetry of thiophene rings as compared to the 6-fold symmetry of benzene rings. The reduced symmetry of thiophene rings results in a restriction on the torsion angle space available to these molecules when bound between two metal electrodes in a junction, causing each molecular junction to sample a different set of conformers in the conductance measurements. By contrast, the rotations of biphenyl are essentially unimpeded by junction binding, allowing each molecular junction

Improved Dye Stability in Single-Molecule Fluorescence Experiments

Science.gov (United States)

EcheverrÍa Aitken, Colin; Marshall, R. Andrew; Pugi, Joseph D.

Complex biological systems challenge existing single-molecule methods. In particular, dye stability limits observation time in singlemolecule fluorescence applications. Current approaches to improving dye performance involve the addition of enzymatic oxygen scavenging systems and small molecule additives. We present an enzymatic oxygen scavenging system that improves dye stability in single-molecule experiments. Compared to the currently-employed glucose-oxidase/catalase system, the protocatechuate-3,4-dioxygenase system achieves lower dissolved oxygen concentration and stabilizes single Cy3, Cy5, and Alexa488 fluorophores. Moreover, this system possesses none of the limitations associated with the glucose oxidase/catalase system. We also tested the effects of small molecule additives in this system. Biological reducing agents significantly destabilize the Cy5 fluorophore as a function of reducing potential. In contrast, anti-oxidants stabilize the Cy3 and Alexa488 fluorophores. We recommend use of the protocatechuate-3,4,-dioxygenase system with antioxidant additives, and in the absence of biological reducing agents. This system should have wide application to single-molecule fluorescence experiments.

Nernst Theorem and Statistical Entropy of 5-Dimensional Rotating Black Hole

Institute of Scientific and Technical Information of China (English)

ZHAO Ren; WU Yue-Qin; ZHANG Li-Chun

2003-01-01

In this paper, by using quantum statistical method, we obtain the partition function of Bose field and Fermi field on the background of the 5-dimensional rotating black hole. Then via the improved brick-wall method and membrane model, we calculate the entropy of Bose field and Fermi field of the black hole. And it is obtained that the entropy of the black hole is not only related to the area of the outer horizon but also is the function of inner horizon's area. In our results, there are not the left out term and the divergent logarithmic term in the original brick-wall method.The doubt that why the entropy of the scalar or Dirac field outside the event horizon is the entropy of the black hole in the original brick-wall method does not exist. The influence of spinning degeneracy of particles on entropy of the black hole is also given. It is shown that the entropy determined by the areas of the inner and outer horizons will approach zero,when the radiation temperature of the black hole approaches absolute zero. It satisfies Nernst theorem. The entropy can be taken as the Planck absolute entropy. We provide a way to study higher dimensional black hole.

Third law of thermodynamics as a key test of generalized entropies.

Science.gov (United States)

Bento, E P; Viswanathan, G M; da Luz, M G E; Silva, R

2015-02-01

The laws of thermodynamics constrain the formulation of statistical mechanics at the microscopic level. The third law of thermodynamics states that the entropy must vanish at absolute zero temperature for systems with nondegenerate ground states in equilibrium. Conversely, the entropy can vanish only at absolute zero temperature. Here we ask whether or not generalized entropies satisfy this fundamental property. We propose a direct analytical procedure to test if a generalized entropy satisfies the third law, assuming only very general assumptions for the entropy S and energy U of an arbitrary N-level classical system. Mathematically, the method relies on exact calculation of β=dS/dU in terms of the microstate probabilities p(i). To illustrate this approach, we present exact results for the two best known generalizations of statistical mechanics. Specifically, we study the Kaniadakis entropy S(κ), which is additive, and the Tsallis entropy S(q), which is nonadditive. We show that the Kaniadakis entropy correctly satisfies the third law only for -1law for q<1. Finally, we give a concrete example of the power of our proposed method by applying it to a paradigmatic system: the one-dimensional ferromagnetic Ising model with nearest-neighbor interactions.

Cell biochemistry studied by single-molecule imaging.

Science.gov (United States)

Mashanov, G I; Nenasheva, T A; Peckham, M; Molloy, J E

2006-11-01

Over the last decade, there have been remarkable developments in live-cell imaging. We can now readily observe individual protein molecules within living cells and this should contribute to a systems level understanding of biological pathways. Direct observation of single fluorophores enables several types of molecular information to be gathered. Temporal and spatial trajectories enable diffusion constants and binding kinetics to be deduced, while analyses of fluorescence lifetime, intensity, polarization or spectra give chemical and conformational information about molecules in their cellular context. By recording the spatial trajectories of pairs of interacting molecules, formation of larger molecular complexes can be studied. In the future, multicolour and multiparameter imaging of single molecules in live cells will be a powerful analytical tool for systems biology. Here, we discuss measurements of single-molecule mobility and residency at the plasma membrane of live cells. Analysis of diffusional paths at the plasma membrane gives information about its physical properties and measurement of temporal trajectories enables rates of binding and dissociation to be derived. Meanwhile, close scrutiny of individual fluorophore trajectories enables ideas about molecular dimerization and oligomerization related to function to be tested directly.

Probing Intranuclear Environments at the Single-Molecule Level

Science.gov (United States)

Grünwald, David; Martin, Robert M.; Buschmann, Volker; Bazett-Jones, David P.; Leonhardt, Heinrich; Kubitscheck, Ulrich; Cardoso, M. Cristina

2008-01-01

Genome activity and nuclear metabolism clearly depend on accessibility, but it is not known whether and to what extent nuclear structures limit the mobility and access of individual molecules. We used fluorescently labeled streptavidin with a nuclear localization signal as an average-sized, inert protein to probe the nuclear environment. The protein was injected into the cytoplasm of mouse cells, and single molecules were tracked in the nucleus with high-speed fluorescence microscopy. We analyzed and compared the mobility of single streptavidin molecules in structurally and functionally distinct nuclear compartments of living cells. Our results indicated that all nuclear subcompartments were easily and similarly accessible for such an average-sized protein, and even condensed heterochromatin neither excluded single molecules nor impeded their passage. The only significant difference was a higher frequency of transient trappings in heterochromatin, which lasted only tens of milliseconds. The streptavidin molecules, however, did not accumulate in heterochromatin, suggesting comparatively less free volume. Interestingly, the nucleolus seemed to exclude streptavidin, as it did many other nuclear proteins, when visualized by conventional fluorescence microscopy. The tracking of single molecules, nonetheless, showed no evidence for repulsion at the border but relatively unimpeded passage through the nucleolus. These results clearly show that single-molecule tracking can provide novel insights into mobility of proteins in the nucleus that cannot be obtained by conventional fluorescence microscopy. Our results suggest that nuclear processes may not be regulated at the level of physical accessibility but rather by local concentration of reactants and availability of binding sites. PMID:18065482

Single molecule image formation, reconstruction and processing: introduction.

Science.gov (United States)

Ashok, Amit; Piestun, Rafael; Stallinga, Sjoerd

2016-07-01

The ability to image at the single molecule scale has revolutionized research in molecular biology. This feature issue presents a collection of articles that provides new insights into the fundamental limits of single molecule imaging and reports novel techniques for image formation and analysis.

Single-Molecule Photocurrent at a Metal-Molecule-Semiconductor Junction.

Science.gov (United States)

Vezzoli, Andrea; Brooke, Richard J; Higgins, Simon J; Schwarzacher, Walther; Nichols, Richard J

2017-11-08

We demonstrate here a new concept for a metal-molecule-semiconductor nanodevice employing Au and GaAs contacts that acts as a photodiode. Current-voltage traces for such junctions are recorded using a STM, and the "blinking" or "I(t)" method is used to record electrical behavior at the single-molecule level in the dark and under illumination, with both low and highly doped GaAs samples and with two different types of molecular bridge: nonconjugated pentanedithiol and the more conjugated 1,4-phenylene(dimethanethiol). Junctions with highly doped GaAs show poor rectification in the dark and a low photocurrent, while junctions with low doped GaAs show particularly high rectification ratios in the dark (>10 3 for a 1.5 V bias potential) and a high photocurrent in reverse bias. In low doped GaAs, the greater thickness of the depletion layer not only reduces the reverse bias leakage current, but also increases the volume that contributes to the photocurrent, an effect amplified by the point contact geometry of the junction. Furthermore, since photogenerated holes tunnel to the metal electrode assisted by the HOMO of the molecular bridge, the choice of the latter has a strong influence on both the steady state and transient metal-molecule-semiconductor photodiode response. The control of junction current via photogenerated charge carriers adds new functionality to single-molecule nanodevices.

A new microcavity design for single molecule detection

International Nuclear Information System (INIS)

Steiner, M.; Schleifenbaum, F.; Stupperich, C.; Failla, A.V.; Hartschuh, A.; Meixner, A.J.

2006-01-01

We present a new microcavity design which allows for efficient detection of single molecules by measuring the molecular fluorescence emission coupled into a resonant cavity mode. The Fabry-Perot-type microresonator consists of two silver mirrors separated by a thin polymer film doped with dye molecules in ultralow concenctration. By slightly tilting one of the mirrors different cavity lengths can be selected within the same sample. Locally, on a μm scale, the microcavity still acts as a planar Fabry-Perot resonator. Using scanning confocal fluorescence microscopy, single emitters on resonance with a single mode of the microresonator can be spatially addressed. Our microcavity is demonstrated to be well-suited for investigating the coupling mechanism between single quantum emitters and single modes of the electromagnetic field. The microcavity layout could be integrated in a lab-on-a-microchip design for ultrasensitive microfluidic analytics and can be considered as an important improvement for single photon sources based on single molecules operating at room temperature

Sensing single electrons with single molecules

International Nuclear Information System (INIS)

Plakhotnik, Taras

2007-01-01

We propose a new methodology for probing transport of just one electron, a process of great importance both in nature and in artificial devices. Our idea for locating a single electron is analogues to the conventional GPS where signals from several satellites are used to locate a macro object. Using fluorescent molecules as tiny sensors, it is possible to determine 3D displacement vector of an electron

Molecular electronics with single molecules in solid-state devices

DEFF Research Database (Denmark)

Moth-Poulsen, Kasper; Bjørnholm, Thomas

2009-01-01

The ultimate aim of molecular electronics is to understand and master single-molecule devices. Based on the latest results on electron transport in single molecules in solid-state devices, we focus here on new insights into the influence of metal electrodes on the energy spectrum of the molecule...

Research Update: Molecular electronics: The single-molecule switch and transistor

Directory of Open Access Journals (Sweden)

Kai Sotthewes

2014-01-01

Full Text Available In order to design and realize single-molecule devices it is essential to have a good understanding of the properties of an individual molecule. For electronic applications, the most important property of a molecule is its conductance. Here we show how a single octanethiol molecule can be connected to macroscopic leads and how the transport properties of the molecule can be measured. Based on this knowledge we have realized two single-molecule devices: a molecular switch and a molecular transistor. The switch can be opened and closed at will by carefully adjusting the separation between the electrical contacts and the voltage drop across the contacts. This single-molecular switch operates in a broad temperature range from cryogenic temperatures all the way up to room temperature. Via mechanical gating, i.e., compressing or stretching of the octanethiol molecule, by varying the contact's interspace, we are able to systematically adjust the conductance of the electrode-octanethiol-electrode junction. This two-terminal single-molecule transistor is very robust, but the amplification factor is rather limited.

The Elusive Nature of Entropy and Its Physical Meaning

Directory of Open Access Journals (Sweden)

Milivoje M. Kostic

2014-02-01

Full Text Available Entropy is the most used and often abused concept in science, but also in philosophy and society. Further confusions are produced by some attempts to generalize entropy with similar but not the same concepts in other disciplines. The physical meaning of phenomenological, thermodynamic entropy is reasoned and elaborated by generalizing Clausius definition with inclusion of generated heat, since it is irrelevant if entropy is changed due to reversible heat transfer or irreversible heat generation. Irreversible, caloric heat transfer is introduced as complementing reversible heat transfer. It is also reasoned and thus proven why entropy cannot be destroyed but is always generated (and thus over-all increased locally and globally, at every space and time scales, without any exception. It is concluded that entropy is a thermal displacement (dynamic thermal-volume of thermal energy due to absolute temperature as a thermal potential (dQ = TdS, and thus associated with thermal heat and absolute temperature, i.e., distribution of thermal energy within thermal micro-particles in space. Entropy is an integral measure of (random thermal energy redistribution (due to heat transfer and/or irreversible heat generation within a material system structure in space, per absolute temperature level: dS = dQSys/T = mCSysdT/T, thus logarithmic integral function, with J/K unit. It may be also expressed as a measure of “thermal disorder”, being related to logarithm of number of all thermal, dynamic microstates W (their position and momenta, S = kBlnW, or to the sum of their logarithmic probabilities S = −kB∑pilnpi, that correspond to, or are consistent with the given thermodynamic macro-state. The number of thermal microstates W, is correlated with macro-properties temperature T and volume V for ideal gases. A system form and/or functional order or disorder are not (thermal energy order/disorder and the former is not related to Thermodynamic entropy. Expanding

Single molecule microscopy and spectroscopy: concluding remarks.

Science.gov (United States)

van Hulst, Niek F

2015-01-01

Chemistry is all about molecules: control, synthesis, interaction and reaction of molecules. All too easily on a blackboard, one draws molecules, their structures and dynamics, to create an insightful picture. The dream is to see these molecules in reality. This is exactly what "Single Molecule Detection" provides: a look at molecules in action at ambient conditions; a breakthrough technology in chemistry, physics and biology. Within the realms of the Royal Society of Chemistry, the Faraday Discussion on "Single Molecule Microscopy and Spectroscopy" was a very appropriate topic for presentation, deliberation and debate. Undoubtedly, the Faraday Discussions have a splendid reputation in stimulating scientific debates along the traditions set by Michael Faraday. Interestingly, back in the 1830's, Faraday himself pursued an experiment that led to the idea that atoms in a compound were joined by an electrical component. He placed two opposite electrodes in a solution of water containing a dissolved compound, and observed that one of the elements of the compound accumulated on one electrode, while the other was deposited on the opposite electrode. Although Faraday was deeply opposed to atomism, he had to recognize that electrical forces were responsible for the joining of atoms. Probably a direct view on the atoms or molecules in his experiment would have convinced him. As such, Michael Faraday might have liked the gathering at Burlington House in September 2015 (). Surely, with the questioning eyes of his bust on the 1st floor corridor, the non-believer Michael Faraday has incited each passer-by to enter into discussion and search for deeper answers at the level of single molecules. In these concluding remarks, highlights of the presented papers and discussions are summarized, complemented by a conclusion on future perspectives.

Single-molecule force-conductance spectroscopy of hydrogen-bonded complexes

Science.gov (United States)

Pirrotta, Alessandro; De Vico, Luca; Solomon, Gemma C.; Franco, Ignacio

2017-03-01

The emerging ability to study physical properties at the single-molecule limit highlights the disparity between what is observable in an ensemble of molecules and the heterogeneous contributions of its constituent parts. A particularly convenient platform for single-molecule studies are molecular junctions where forces and voltages can be applied to individual molecules, giving access to a series of electromechanical observables that can form the basis of highly discriminating multidimensional single-molecule spectroscopies. Here, we computationally examine the ability of force and conductance to inform about molecular recognition events at the single-molecule limit. For this, we consider the force-conductance characteristics of a prototypical class of hydrogen bonded bimolecular complexes sandwiched between gold electrodes. The complexes consist of derivatives of a barbituric acid and a Hamilton receptor that can form up to six simultaneous hydrogen bonds. The simulations combine classical molecular dynamics of the mechanical deformation of the junction with non-equilibrium Green's function computations of the electronic transport. As shown, in these complexes hydrogen bonds mediate transport either by directly participating as a possible transport pathway or by stabilizing molecular conformations with enhanced conductance properties. Further, we observe that force-conductance correlations can be very sensitive to small changes in the chemical structure of the complexes and provide detailed information about the behavior of single molecules that cannot be gleaned from either measurement alone. In fact, there are regions during the elongation that are only mechanically active, others that are only conductance active, and regions where both force and conductance changes as the complex is mechanically manipulated. The implication is that force and conductance provide complementary information about the evolution of molecules in junctions that can be used to

Semisynthetic protein nanoreactor for single-molecule chemistry

OpenAIRE

Lee, Joongoo; Bayley, Hagan

2015-01-01

The modulation of ionic current flowing through an individual protein pore provides information at the single-molecule level about chemical reactions occurring within the pore. However, chemistry investigated in this way has been largely confined to the reactions of thiolates, presented by the side chains of cysteine residues. The introduction of unnatural amino acids would provide a large variety of reactive side chains with which additional single-molecule chemistry could be investigated. H...

Modulation and Control of Charge Transport Through Single-Molecule Junctions.

Science.gov (United States)

Wang, Kun; Xu, Bingqian

2017-02-01

The ability to modulate and control charge transport though single-molecule junction devices is crucial to achieving the ultimate goal of molecular electronics: constructing real-world-applicable electronic components from single molecules. This review aims to highlight the progress made in single-molecule electronics, emphasizing the development of molecular junction electronics in recent years. Among many techniques that attempt to wire a molecule to metallic electrodes, the single-molecule break junction (SMBJ) technique is one of the most reliable and tunable experimental platforms for achieving metal-molecule-metal configurations. It also provides great freedom to tune charge transport through the junction. Soon after the SMBJ technique was introduced, it was extensively used to measure the conductances of individual molecules; however, different conductances were obtained for the same molecule, and it proved difficult to interpret this wide distribution of experimental data. This phenomenon was later found to be mainly due to a lack of precise experimental control and advanced data analysis methods. In recent years, researchers have directed considerable effort into advancing the SMBJ technique by gaining a deeper physical understanding of charge transport through single molecules and thus enhancing its potential applicability in functional molecular-scale electronic devices, such as molecular diodes and molecular transistors. In parallel with that research, novel data analysis methods and approaches that enable the discovery of hidden yet important features in the data are being developed. This review discusses various aspects of molecular junction electronics, from the initial goal of molecular electronics, the development of experimental techniques for creating single-molecule junctions and determining single-molecule conductance, to the characterization of functional current-voltage features and the investigation of physical properties other than charge

Single Molecules as Optical Probes for Structure and Dynamics

Science.gov (United States)

Orrit, Michel

Single molecules and single nanoparticles are convenient links between the nanoscale world and the laboratory. We discuss the limits for their optical detection by three different methods: fluorescence, direct absorption, and photothermal detection. We briefly review some recent illustrations of qualitatively new information gathered from single-molecule signals: intermittency of the fluorescence intensity, acoustic vibrations of nanoparticles (1-100 GHz) or of extended defects in molecular crystals (0.1-1 MHz), and dynamical heterogeneity in glass-forming molecular liquids. We conclude with an outlook of future uses of single-molecule methods in physical chemistry, soft matter, and material science.

Single-Molecule Nanomagnets

Science.gov (United States)

Friedman, Jonathan R.; Sarachik, Myriam P.

2010-04-01

Single-molecule magnets straddle the classical and quantum mechanical worlds, displaying many fascinating phenomena. They may have important technological applications in information storage and quantum computation. We review the physical properties of two prototypical molecular nanomagnets, Mn12-acetate and Fe8: Each behaves as a rigid, spin-10 object and exhibits tunneling between up and down directions. As temperature is lowered, the spin-reversal process evolves from thermal activation to pure quantum tunneling. At low temperatures, magnetic avalanches occur in which the magnetization of an entire sample rapidly reverses. We discuss the important role that symmetry-breaking fields play in driving tunneling and in producing Berry-phase interference. Recent experimental advances indicate that quantum coherence can be maintained on timescales sufficient to allow a meaningful number of quantum computing operations to be performed. Efforts are under way to create monolayers and to address and manipulate individual molecules.

Entropy for theories with indefinite causal structure

International Nuclear Information System (INIS)

Markes, Sonia; Hardy, Lucien

2011-01-01

Any theory with definite causal structure has a defined past and future, be it defined by light cones or an absolute time scale. Entropy is a concept that has traditionally been reliant on a definite notion of causality. However, without a definite notion of causality, the concept of entropy is not all lost. Indefinite causal structure results from combining probabilistic predictions and dynamical space-time. The causaloid framework lays the mathematical groundwork to be able to treat indefinite causal structure. In this paper, we build on the causaloid mathematics and define a causally-unbiased entropy for an indefinite causal structure. In defining a causally-unbiased entropy, there comes about an emergent idea of causality in the form of a measure of causal connectedness, termed the Q factor.

Identification of Auditory Object-Specific Attention from Single-Trial Electroencephalogram Signals via Entropy Measures and Machine Learning

Directory of Open Access Journals (Sweden)

Yun Lu

2018-05-01

Full Text Available Existing research has revealed that auditory attention can be tracked from ongoing electroencephalography (EEG signals. The aim of this novel study was to investigate the identification of peoples’ attention to a specific auditory object from single-trial EEG signals via entropy measures and machine learning. Approximate entropy (ApEn, sample entropy (SampEn, composite multiscale entropy (CmpMSE and fuzzy entropy (FuzzyEn were used to extract the informative features of EEG signals under three kinds of auditory object-specific attention (Rest, Auditory Object1 Attention (AOA1 and Auditory Object2 Attention (AOA2. The linear discriminant analysis and support vector machine (SVM, were used to construct two auditory attention classifiers. The statistical results of entropy measures indicated that there were significant differences in the values of ApEn, SampEn, CmpMSE and FuzzyEn between Rest, AOA1 and AOA2. For the SVM-based auditory attention classifier, the auditory object-specific attention of Rest, AOA1 and AOA2 could be identified from EEG signals using ApEn, SampEn, CmpMSE and FuzzyEn as features and the identification rates were significantly different from chance level. The optimal identification was achieved by the SVM-based auditory attention classifier using CmpMSE with the scale factor τ = 10. This study demonstrated a novel solution to identify the auditory object-specific attention from single-trial EEG signals without the need to access the auditory stimulus.

Quantum design rules for single molecule logic gates.

Science.gov (United States)

Renaud, N; Hliwa, M; Joachim, C

2011-08-28

Recent publications have demonstrated how to implement a NOR logic gate with a single molecule using its interaction with two surface atoms as logical inputs [W. Soe et al., ACS Nano, 2011, 5, 1436]. We demonstrate here how this NOR logic gate belongs to the general family of quantum logic gates where the Boolean truth table results from a full control of the quantum trajectory of the electron transfer process through the molecule by very local and classical inputs practiced on the molecule. A new molecule OR gate is proposed for the logical inputs to be also single metal atoms, one per logical input.

Ordered array of CoPc-vacancies filled with single-molecule rotors

Science.gov (United States)

Xie, Zheng-Bo; Wang, Ya-Li; Tao, Min-Long; Sun, Kai; Tu, Yu-Bing; Yuan, Hong-Kuan; Wang, Jun-Zhong

2018-05-01

We report the highly ordered array of CoPc-vacancies and the single-molecule rotors inside the vacancies. When CoPc molecules are deposited on Cd(0001) at low-temperature, three types of molecular vacancies appeared randomly in the CoPc monolayer. Annealing the sample to higher temperature leads to the spontaneous phase separation and self-organized arrangement of the vacancies. Highly ordered arrays of two-molecule vacancies and single-molecule vacancies have been obtained. In particular, there is a rotating CoPc molecule inside each single-molecule vacancy, which constitutes the array of single-molecule rotors. These results provide a new routine to fabricate the nano-machines on a large scale.

Supramolecular Systems and Chemical Reactions in Single-Molecule Break Junctions.

Science.gov (United States)

Li, Xiaohui; Hu, Duan; Tan, Zhibing; Bai, Jie; Xiao, Zongyuan; Yang, Yang; Shi, Jia; Hong, Wenjing

2017-04-01

The major challenges of molecular electronics are the understanding and manipulation of the electron transport through the single-molecule junction. With the single-molecule break junction techniques, including scanning tunneling microscope break junction technique and mechanically controllable break junction technique, the charge transport through various single-molecule and supramolecular junctions has been studied during the dynamic fabrication and continuous characterization of molecular junctions. This review starts from the charge transport characterization of supramolecular junctions through a variety of noncovalent interactions, such as hydrogen bond, π-π interaction, and electrostatic force. We further review the recent progress in constructing highly conductive molecular junctions via chemical reactions, the response of molecular junctions to external stimuli, as well as the application of break junction techniques in controlling and monitoring chemical reactions in situ. We suggest that beyond the measurement of single molecular conductance, the single-molecule break junction techniques provide a promising access to study molecular assembly and chemical reactions at the single-molecule scale.

Electrochemical proton relay at the single-molecule level

DEFF Research Database (Denmark)

Kuznetsov, A. M.; Medvedev, I. G.; Ulstrup, Jens

2009-01-01

A scheme for the experimental study of single-proton transfer events, based on proton-coupled two-electron transfer between a proton donor and a proton acceptor molecule confined in the tunneling gap between two metal leads in electrolyte solution is suggested. Expressions for the electric current...... are derived and compared with formalism for electron tunneling through redox molecules. The scheme allows studying the kinetics of proton and hydrogen atom transfer as well as kinetic isotope effects at the single-molecule level under electrochemical potential control....

Coherent interaction of single molecules and plasmonic nanowires

Science.gov (United States)

Gerhardt, Ilja; Grotz, Bernhard; Siyushev, Petr; Wrachtrup, Jörg

2017-09-01

Quantum plasmonics opens the option to integrate complex quantum optical circuitry onto chip scale devices. In the past, often external light sources were used and nonclassical light was coupled in and out of plasmonic structures, such as hole arrays or waveguide structures. Another option to launch single plasmonic excitations is the coupling of single emitters in the direct proximity of, e.g., a silver or gold nanostructure. Here, we present our attempts to integrate the research of single emitters with wet-chemically grown silver nanowires. The emitters of choice are single organic dye molecules under cryogenic conditions, which are known to act as high-brightness and extremely narrow-band single photon sources. Another advantage is their high optical nonlinearity, such that they might mediate photon-photon interactions on the nanoscale. We report on the coupling of a single molecule fluorescence emission through the wire over the length of several wavelengths. The transmission of coherently emitted photons is proven by an extinction type experiment. As for influencing the spectral properties of a single emitter, we are able to show a remote change of the line-width of a single terrylene molecule, which is in close proximity to the nanowire.

Absolute Configuration from Different Multifragmentation Pathways in Light-Induced Coulomb Explosion Imaging.

Science.gov (United States)

Pitzer, Martin; Kastirke, Gregor; Kunitski, Maksim; Jahnke, Till; Bauer, Tobias; Goihl, Christoph; Trinter, Florian; Schober, Carl; Henrichs, Kevin; Becht, Jasper; Zeller, Stefan; Gassert, Helena; Waitz, Markus; Kuhlins, Andreas; Sann, Hendrik; Sturm, Felix; Wiegandt, Florian; Wallauer, Robert; Schmidt, Lothar Ph H; Johnson, Allan S; Mazenauer, Manuel; Spenger, Benjamin; Marquardt, Sabrina; Marquardt, Sebastian; Schmidt-Böcking, Horst; Stohner, Jürgen; Dörner, Reinhard; Schöffler, Markus; Berger, Robert

2016-08-18

The absolute configuration of individual small molecules in the gas phase can be determined directly by light-induced Coulomb explosion imaging (CEI). Herein, this approach is demonstrated for ionization with a single X-ray photon from a synchrotron light source, leading to enhanced efficiency and faster fragmentation as compared to previous experiments with a femtosecond laser. In addition, it is shown that even incomplete fragmentation pathways of individual molecules from a racemic CHBrClF sample can give access to the absolute configuration in CEI. This leads to a significant increase of the applicability of the method as compared to the previously reported complete break-up into atomic ions and can pave the way for routine stereochemical analysis of larger chiral molecules by light-induced CEI. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Absolute single electron loss in collisions of Ar+ with various atoms

Science.gov (United States)

Reyes, P. G.; Martínez, H.; Castillo, F.

2001-07-01

Absolute differential and total cross sections for single electron loss were measured for Ar+ ions on various atoms in the energy range of 1.5 to 5.0 keV. The laboratory angular scan for the distributions ranged from -2.5 to 2.5 degrees. The measured differential cross sections have been integrated over the experimental angular range providing absolute total cross sections. The behavior of the total electron loss cross sections with the target atomic number, Zt, shows different dependences as the collision energy increases. In all cases it displays a saturation as Zt increases.

The spontaneous formation of single-molecule junctions via terminal alkynes

International Nuclear Information System (INIS)

Pla-Vilanova, Pepita; Aragonès, Albert C; Sanz, Fausto; Darwish, Nadim; Diez-Perez, Ismael; Ciampi, Simone

2015-01-01

Herein, we report the spontaneous formation of single-molecule junctions via terminal alkyne contact groups. Self-assembled monolayers that form spontaneously from diluted solutions of 1, 4-diethynylbenzene (DEB) were used to build single-molecule contacts and assessed using the scanning tunneling microscopy-break junction technique (STM-BJ). The STM-BJ technique in both its dynamic and static approaches was used to characterize the lifetime (stability) and the conductivity of a single-DEB wire. It is demonstrated that single-molecule junctions form spontaneously with terminal alkynes and require no electrochemical control or chemical deprotonation. The alkyne anchoring group was compared against typical contact groups exploited in single-molecule studies, i.e. amine (benzenediamine) and thiol (benzendithiol) contact groups. The alkyne contact showed a conductance magnitude comparable to that observed with amine and thiol groups. The lifetime of the junctions formed from alkynes were only slightly less than that of thiols and greater than that observed for amines. These findings are important as (a) they extend the repertoire of chemical contacts used in single-molecule measurements to 1-alkynes, which are synthetically accessible and stable and (b) alkynes have a remarkable affinity toward silicon surfaces, hence opening the door for the study of single-molecule transport on a semiconducting electronic platform. (fast track communication)

Central dogma at the single-molecule level in living cells.

Science.gov (United States)

Li, Gene-Wei; Xie, X Sunney

2011-07-20

Gene expression originates from individual DNA molecules within living cells. Like many single-molecule processes, gene expression and regulation are stochastic, that is, sporadic in time. This leads to heterogeneity in the messenger-RNA and protein copy numbers in a population of cells with identical genomes. With advanced single-cell fluorescence microscopy, it is now possible to quantify transcriptomes and proteomes with single-molecule sensitivity. Dynamic processes such as transcription-factor binding, transcription and translation can be monitored in real time, providing quantitative descriptions of the central dogma of molecular biology and the demonstration that a stochastic single-molecule event can determine the phenotype of a cell.

Torque Measurement at the Single Molecule Level

Science.gov (United States)

Forth, Scott; Sheinin, Maxim Y.; Inman, James; Wang, Michelle D.

2017-01-01

Methods for exerting and measuring forces on single molecules have revolutionized the study of the physics of biology. However, it is often the case that biological processes involve rotation or torque generation, and these parameters have been more difficult to access experimentally. Recent advances in the single molecule field have led to the development of techniques which add the capability of torque measurement. By combining force, displacement, torque, and rotational data, a more comprehensive description of the mechanics of a biomolecule can be achieved. In this review, we highlight a number of biological processes for which torque plays a key mechanical role. We describe the various techniques that have been developed to directly probe the torque experienced by a single molecule, and detail a variety of measurements made to date using these new technologies. We conclude by discussing a number of open questions and propose systems of study which would be well suited for analysis with torsional measurement techniques. PMID:23541162

Rotation of a single molecule within a supramolecular bearing

DEFF Research Database (Denmark)

Gimzewski, J.K.; Joachim, C.; Schlittler, R.R.

1998-01-01

Experimental visualization and verification of a single-molecule rotor operating within a supramolecular bearing is reported. Using a scanning tunneling microscope, single molecules were observed to exist in one of two spatially defined states Laterally separated by 0.26 nanometers. One...

Molecular electronics with single molecules in solid-state devices.

Science.gov (United States)

Moth-Poulsen, Kasper; Bjørnholm, Thomas

2009-09-01

The ultimate aim of molecular electronics is to understand and master single-molecule devices. Based on the latest results on electron transport in single molecules in solid-state devices, we focus here on new insights into the influence of metal electrodes on the energy spectrum of the molecule, and on how the electron transport properties of the molecule depend on the strength of the electronic coupling between it and the electrodes. A variety of phenomena are observed depending on whether this coupling is weak, intermediate or strong.

Single-molecule imaging and manipulation of biomolecular machines and systems.

Science.gov (United States)

Iino, Ryota; Iida, Tatsuya; Nakamura, Akihiko; Saita, Ei-Ichiro; You, Huijuan; Sako, Yasushi

2018-02-01

Biological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration. We provide an overview of single-molecule imaging methods involving both small and large probes used to monitor the dynamic motions of molecular machines in vitro (purified proteins) and in living cells, and single-molecule manipulation methods used to measure the forces, mechanical properties and responses of biomolecules. We also introduce several examples of single-molecule analysis, focusing primarily on motor proteins and signal transduction systems. Single-molecule analysis is a powerful approach to unveil the operational mechanisms both of individual molecular machines and of systems consisting of many molecular machines. Quantitative, high-resolution single-molecule analyses of biomolecular systems at the various hierarchies of life will help to answer our fundamental question: "What is life?" This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. Copyright © 2017 Elsevier B.V. All rights reserved.

A plasmonic biosensor with single-molecule sensitivity

NARCIS (Netherlands)

Zijlstra, P.; Paulo, P.M.R.; Yuan, H.; Khatua, S.; Yorulmaz, M.; Orrit, M.

2013-01-01

The plasmon resonance of a single metal nanoparticle induces an enhancement of the local electromagnetic field. We exploit this field enhancement to detect single molecules that are (1) poorly fluorescent or (2) completely non-fluorescent.

Molecular electronics--resonant transport through single molecules.

Science.gov (United States)

Lörtscher, Emanuel; Riel, Heike

2010-01-01

The mechanically controllable break-junction technique (MCBJ) enables us to investigate charge transport through an individually contacted and addressed molecule in ultra-high vacuum (UHV) environment at variable temperature ranging from room temperature down to 4 K. Using a statistical measurement and analysis approach, we acquire current-voltage (I-V) characteristics during the repeated formation, manipulation, and breaking of a molecular junction. At low temperatures, voltages accessing the first molecular orbitals in resonance can be applied, providing spectroscopic information about the junction's energy landscape, in particular about the molecular level alignment in respect to the Fermi energy of the electrodes. Thereby, we can investigate the non-linear transport properties of various types of functional molecules and explore their potential use as functional building blocks for future nano-electronics. An example will be given by the reversible and controllable switching between two distinct conductive states of a single molecule. As a proof-of-principle for functional molecular devices, a single-molecule memory element will be demonstrated.

Quantum dynamical entropy revisited

International Nuclear Information System (INIS)

Hudetz, T.

1996-10-01

We define a new quantum dynamical entropy, which is a 'hybrid' of the closely related, physically oriented entropy introduced by Alicki and Fannes in 1994, and of the mathematically well-developed, single-argument entropy introduced by Connes, Narnhofer and Thirring in 1987. We show that this new quantum dynamical entropy has many properties similar to the ones of the Alicki-Fannes entropy, and also inherits some additional properties from the CNT entropy. In particular, the 'hybrid' entropy interpolates between the two different ways in which both the AF and the CNT entropy of the shift automorphism on the quantum spin chain agree with the usual quantum entropy density, resulting in even better agreement. Also, the new quantum dynamical entropy generalizes the classical dynamical entropy of Kolmogorov and Sinai in the same way as does the AF entropy. Finally, we estimate the 'hybrid' entropy both for the Powers-Price shift systems and for the noncommutative Arnold map on the irrational rotation C * -algebra, leaving some interesting open problems. (author)

Structural contributions to the third-law entropy of uranyl phases

International Nuclear Information System (INIS)

Chen, F.; Ewing, R.C.

1999-01-01

Entropies that are used in geochemical calculations are usually based on calorimetric measurements. However, because of the contributions of neglected residual entropies which cannot be determined by calorimetric measurements, the true third-law entropies for many phases may be quite different from those derived from thermal data. The residual entropies are caused by site-mixing, structural disorder and magnetic spin disorder and may result in a considerable contribution to the third-law entropy of solid phases. Magnetic spin-configurational entropy is not expected to be significant in uranyl phases. However, because most uranyl phases are based on sheet or chain structures and usually contain several molecular water groups, site-mixing, vacancies, as well as disorder in the orientation of hydrogen bonds and the polar H 2 O molecules may occur. Calculations of the ideal site-mixing configurational entropy for some uranyl phases indicate that the residual contributions that arise from substitution and vacancies to the third-law entropies of uranyl phases may be large. A brief examination of the crystal chemistry of water molecules in uranyl phases suggests that considerable residual entropy may be caused by the disorder of hydrogen bonds associated with interstitial H 2 O groups

Stereoelectronic Effect-Induced Conductance Switching in Aromatic Chain Single-Molecule Junctions.

Science.gov (United States)

Xin, Na; Wang, Jinying; Jia, Chuancheng; Liu, Zitong; Zhang, Xisha; Yu, Chenmin; Li, Mingliang; Wang, Shuopei; Gong, Yao; Sun, Hantao; Zhang, Guanxin; Liu, Zhirong; Zhang, Guangyu; Liao, Jianhui; Zhang, Deqing; Guo, Xuefeng

2017-02-08

Biphenyl, as the elementary unit of organic functional materials, has been widely used in electronic and optoelectronic devices. However, over decades little has been fundamentally understood regarding how the intramolecular conformation of biphenyl dynamically affects its transport properties at the single-molecule level. Here, we establish the stereoelectronic effect of biphenyl on its electrical conductance based on the platform of graphene-molecule single-molecule junctions, where a specifically designed hexaphenyl aromatic chain molecule is covalently sandwiched between nanogapped graphene point contacts to create stable single-molecule junctions. Both theoretical and temperature-dependent experimental results consistently demonstrate that phenyl twisting in the aromatic chain molecule produces different microstates with different degrees of conjugation, thus leading to stochastic switching between high- and low-conductance states. These investigations offer new molecular design insights into building functional single-molecule electrical devices.

A single molecule DNA flow stretching microscope for undergraduates

NARCIS (Netherlands)

Williams, Kelly; Grafe, Brendan; Burke, Kathryn M.; Tanner, Nathan; van Oijen, Antoine M.; Loparo, Joseph; Price, Allen C.

2011-01-01

The design of a simple, safe, and inexpensive single molecule flow stretching instrument is presented. The instrument uses a low cost upright microscope coupled to a webcam for imaging single DNA molecules that are tethered in an easy to construct microfluidic flow cell. The system requires no

Single particle tracking and single molecule energy transfer

CERN Document Server

Bräuchle, Christoph; Michaelis, Jens

2009-01-01

Closing a gap in the literature, this handbook gathers all the information on single particle tracking and single molecule energy transfer. It covers all aspects of this hot and modern topic, from detecting virus entry to membrane diffusion, and from protein folding using spFRET to coupled dye systems, as well recent achievements in the field. Throughout, the first-class editors and top international authors present content of the highest quality, making this a must-have for physical chemists, spectroscopists, molecular physicists and biochemists.

Thermodynamic optimization of ground heat exchangers with single U-tube by entropy generation minimization method

International Nuclear Information System (INIS)

Li Min; Lai, Alvin C.K.

2013-01-01

Highlights: ► A second-law-based analysis is performed for single U-tube ground heat exchangers. ► Two expressions for the optimal length and flow velocity are developed for GHEs. ► Empirical velocities of GHEs are large compared to thermodynamic optimum values. - Abstract: This paper investigates thermodynamic performance of borehole ground heat exchangers with a single U-tube by the entropy generation minimization method which requires information of heat transfer and fluid mechanics, in addition to thermodynamics analysis. This study first derives an expression for dimensionless entropy generation number, a function that consists of five dimensionless variables, including Reynolds number, dimensionless borehole length, scale factor of pressures, and two duty parameters of ground heat exchangers. The derivation combines a heat transfer model and a hydraulics model for borehole ground heat exchangers with the first law and the second law of thermodynamics. Next, the entropy generation number is minimized to produce two analytical expressions for the optimal length and the optimal flow velocity of ground heat exchangers. Then, this paper discusses and analyzes implications and applications of these optimization formulas with two case studies. An important finding from the case studies is that widely used empirical velocities of circulating fluid are too large to operate ground-coupled heat pump systems in a thermodynamic optimization way. This paper demonstrates that thermodynamic optimal parameters of ground heat exchangers can probably be determined by using the entropy generation minimization method.

Electrons, Photons, and Force: Quantitative Single-Molecule Measurements from Physics to Biology

Science.gov (United States)

2011-01-01

Single-molecule measurement techniques have illuminated unprecedented details of chemical behavior, including observations of the motion of a single molecule on a surface, and even the vibration of a single bond within a molecule. Such measurements are critical to our understanding of entities ranging from single atoms to the most complex protein assemblies. We provide an overview of the strikingly diverse classes of measurements that can be used to quantify single-molecule properties, including those of single macromolecules and single molecular assemblies, and discuss the quantitative insights they provide. Examples are drawn from across the single-molecule literature, ranging from ultrahigh vacuum scanning tunneling microscopy studies of adsorbate diffusion on surfaces to fluorescence studies of protein conformational changes in solution. PMID:21338175

Biological Nanopores: Confined Spaces for Electrochemical Single-Molecule Analysis.

Science.gov (United States)

Cao, Chan; Long, Yi-Tao

2018-02-20

Nanopore sensing is developing into a powerful single-molecule approach to investigate the features of biomolecules that are not accessible by studying ensemble systems. When a target molecule is transported through a nanopore, the ions occupying the pore are excluded, resulting in an electrical signal from the intermittent ionic blockade event. By statistical analysis of the amplitudes, duration, frequencies, and shapes of the blockade events, many properties of the target molecule can be obtained in real time at the single-molecule level, including its size, conformation, structure, charge, geometry, and interactions with other molecules. With the development of the use of α-hemolysin to characterize individual polynucleotides, nanopore technology has attracted a wide range of research interest in the fields of biology, physics, chemistry, and nanoscience. As a powerful single-molecule analytical method, nanopore technology has been applied for the detection of various biomolecules, including oligonucleotides, peptides, oligosaccharides, organic molecules, and disease-related proteins. In this Account, we highlight recent developments of biological nanopores in DNA-based sensing and in studying the conformational structures of DNA and RNA. Furthermore, we introduce the application of biological nanopores to investigate the conformations of peptides affected by charge, length, and dipole moment and to study disease-related proteins' structures and aggregation transitions influenced by an inhibitor, a promoter, or an applied voltage. To improve the sensing ability of biological nanopores and further extend their application to a wider range of molecular sensing, we focus on exploring novel biological nanopores, such as aerolysin and Stable Protein 1. Aerolysin exhibits an especially high sensitivity for the detection of single oligonucleotides both in current separation and duration. Finally, to facilitate the use of nanopore measurements and statistical analysis

Synthesis of single-molecule nanocars.

Science.gov (United States)

Vives, Guillaume; Tour, James M

2009-03-17

The drive to miniaturize devices has led to a variety of molecular machines inspired by macroscopic counterparts such as molecular motors, switches, shuttles, turnstiles, barrows, elevators, and nanovehicles. Such nanomachines are designed for controlled mechanical motion and the transport of nanocargo. As researchers miniaturize devices, they can consider two complementary approaches: (1) the "top-down" approach, which reduces the size of macroscopic objects to reach an equivalent microscopic entity using photolithography and related techniques and (2) the "bottom-up" approach, which builds functional microscopic or nanoscopic entities from molecular building blocks. The top-down approach, extensively used by the semiconductor industry, is nearing its scaling limits. On the other hand, the bottom-up approach takes advantage of the self-assembly of smaller molecules into larger networks by exploiting typically weak molecular interactions. But self-assembly alone will not permit complex assembly. Using nanomachines, we hope to eventually consider complex, enzyme-like directed assembly. With that ultimate goal, we are currently exploring the control of nanomachines that would provide a basis for the future bottom-up construction of complex systems. This Account describes the synthesis of a class of molecular machines that resemble macroscopic vehicles. We designed these so-called nanocars for study at the single-molecule level by scanning probe microscopy (SPM). The vehicles have a chassis connected to wheel-terminated axles and convert energy inputs such as heat, electric fields, or light into controlled motion on a surface, ultimately leading to transport of nanocargo. At first, we used C(60) fullerenes as wheels, which allowed the demonstration of a directional rolling mechanism of a nanocar on a gold surface by STM. However, because of the low solubility of the fullerene nanocars and the incompatibility of fullerenes with photochemical processes, we developed new

Studies of G-quadruplex DNA structures at the single molecule level

DEFF Research Database (Denmark)

Kragh, Sofie Louise

2015-01-01

Folding of G-quaduplex structures adopted by the human telomeric repeat is here studied by single molecule FRET microscopy. This method allows for the investigation of G-quadruplex structures and their conformational dynamic. Telomeres are located at the ends of our chromosomes and end in a single...... with human telomeric repeat adopt several different G-quadruplex conformations in the presence of K+ ions. G-quadruplexes inhibit telomerase activity and are therefore potential targets for anti-cancer drugs, which can be small molecule ligands capable of stabilizing G-quadruplex structures. Understanding...... range. FRET spectroscopy can be performed on an ensemble of molecules, or on the single molecule level. In single molecule FRET experiments it is possible to follow the behaviour in time for each molecule independently, allowing insight into both dynamically and statistically heterogeneous molecular...

Automated imaging system for single molecules

Science.gov (United States)

Schwartz, David Charles; Runnheim, Rodney; Forrest, Daniel

2012-09-18

There is provided a high throughput automated single molecule image collection and processing system that requires minimal initial user input. The unique features embodied in the present disclosure allow automated collection and initial processing of optical images of single molecules and their assemblies. Correct focus may be automatically maintained while images are collected. Uneven illumination in fluorescence microscopy is accounted for, and an overall robust imaging operation is provided yielding individual images prepared for further processing in external systems. Embodiments described herein are useful in studies of any macromolecules such as DNA, RNA, peptides and proteins. The automated image collection and processing system and method of same may be implemented and deployed over a computer network, and may be ergonomically optimized to facilitate user interaction.

Single-molecule force-conductance spectroscopy of hydrogen-bonded complexes

DEFF Research Database (Denmark)

Pirrotta, Alessandro; De Vico, Luca; Solomon, Gemma C.

2017-01-01

to inform about molecular recognition events at the single-molecule limit. For this, we consider the force-conductance characteristics of a prototypical class of hydrogen bonded bimolecular complexes sandwiched between gold electrodes. The complexes consist of derivatives of a barbituric acid and a Hamilton...... is mechanically manipulated. The implication is that force and conductance provide complementary information about the evolution of molecules in junctions that can be used to interrogate basic structure-transport relations at the single-molecule limit....

Fast temporal fluctuations in single-molecule junctions.

Science.gov (United States)

Ochs, Roif; Secker, Daniel; Elbing, Mark; Mayor, Marcel; Weber, Heiko B

2006-01-01

The noise within the electrical current through single-molecule junctions is studied cryogenic temperature. The organic sample molecules were contacted with the mechanically controlled break-junction technique. The noise spectra refer to a where only few Lorentzian fluctuators occur in the conductance. The frequency dependence shows qualitative variations from sample to sample.

Electrochemistry and bioelectrochemistry towards the single-molecule level: Theoretical notions and systems

International Nuclear Information System (INIS)

Zhang Jingdong; Chi Qijin; Albrecht, Tim; Kuznetsov, Alexander M.; Grubb, Mikala; Hansen, Allan G.; Wackerbarth, Hainer; Welinder, Anne C.; Ulstrup, Jens

2005-01-01

Surface structures controlled at the nanometer and single-molecule levels, with functions crucially determined by interfacial electron transfer (ET) are broadly reported in recent years, with different kinds of electrochemically controlled nanoscale/single molecule systems. One is the broad class of metallic and semiconductor-based nanoparticles, nano-arrays, nanotubes, and nanopits. Others are based on self-assembled molecular monolayers. The latter extend to bioelectrochemical systems with redox metalloproteins and DNA-based molecules as targets. We overview here some recent achievements in areas of interfacial electrochemical ET systems, mapped to the nanoscale and single-molecule levels. Focus is on both experimental and theoretical studies in our group. Systems addressed are organized monolayers of redox active transition metal complexes, and metalloproteins and metalloenzymes on single-crystal Au(1 1 1)-electrode surfaces. These systems have been investigated by voltammetry, spectroscopy, microcantilever technology, and scanning probe microscopy. A class of Os-complexes has shown suitable as targets for electrochemical in situ scanning tunnelling microscopy (STM), with close to single-molecule scanning tunnelling spectroscopic (STS) features. Mapping of redox metalloproteins from the three major classes, i.e. blue copper proteins, heme proteins, and iron-sulfur proteins, at the monolayer and single-molecule levels have also been achieved. In situ STM and spectroscopy of redox molecules and biomolecules have been supported by new theoretical frames, which extend established theory of interfacial electrochemical ET. The electrochemical nanoscale and single-molecule systems discussed are compared with other recent nanoscale and single-molecule systems with conspicuous device-like properties, particularly unimolecular rectifiers and single-molecule transistors. Both of these show analogies to electrochemical in situ STM features of redox molecules and

Single-molecule electronics: Cooling individual vibrational modes by the tunneling current.

Science.gov (United States)

Lykkebo, Jacob; Romano, Giuseppe; Gagliardi, Alessio; Pecchia, Alessandro; Solomon, Gemma C

2016-03-21

Electronic devices composed of single molecules constitute the ultimate limit in the continued downscaling of electronic components. A key challenge for single-molecule electronics is to control the temperature of these junctions. Controlling heating and cooling effects in individual vibrational modes can, in principle, be utilized to increase stability of single-molecule junctions under bias, to pump energy into particular vibrational modes to perform current-induced reactions, or to increase the resolution in inelastic electron tunneling spectroscopy by controlling the life-times of phonons in a molecule by suppressing absorption and external dissipation processes. Under bias the current and the molecule exchange energy, which typically results in heating of the molecule. However, the opposite process is also possible, where energy is extracted from the molecule by the tunneling current. Designing a molecular "heat sink" where a particular vibrational mode funnels heat out of the molecule and into the leads would be very desirable. It is even possible to imagine how the vibrational energy of the other vibrational modes could be funneled into the "cooling mode," given the right molecular design. Previous efforts to understand heating and cooling mechanisms in single molecule junctions have primarily been concerned with small models, where it is unclear which molecular systems they correspond to. In this paper, our focus is on suppressing heating and obtaining current-induced cooling in certain vibrational modes. Strategies for cooling vibrational modes in single-molecule junctions are presented, together with atomistic calculations based on those strategies. Cooling and reduced heating are observed for two different cooling schemes in calculations of atomistic single-molecule junctions.

Multiplexed single-molecule force spectroscopy using a centrifuge.

Science.gov (United States)

Yang, Darren; Ward, Andrew; Halvorsen, Ken; Wong, Wesley P

2016-03-17

We present a miniature centrifuge force microscope (CFM) that repurposes a benchtop centrifuge for high-throughput single-molecule experiments with high-resolution particle tracking, a large force range, temperature control and simple push-button operation. Incorporating DNA nanoswitches to enable repeated interrogation by force of single molecular pairs, we demonstrate increased throughput, reliability and the ability to characterize population heterogeneity. We perform spatiotemporally multiplexed experiments to collect 1,863 bond rupture statistics from 538 traceable molecular pairs in a single experiment, and show that 2 populations of DNA zippers can be distinguished using per-molecule statistics to reduce noise.

Arithmetic of quantum entropy function

International Nuclear Information System (INIS)

Sen, Ashoke

2009-01-01

Quantum entropy function is a proposal for computing the entropy associated with the horizon of a black hole in the extremal limit, and is related via AdS/CFT correspondence to the dimension of the Hilbert space in a dual quantum mechanics. We show that in N = 4 supersymmetric string theories, quantum entropy function formalism naturally explains the origin of the subtle differences between the microscopic degeneracies of quarter BPS dyons carrying different torsion, i.e. different arithmetical properties. These arise from additional saddle points in the path integral - whose existence depends on the arithmetical properties of the black hole charges - constructed as freely acting orbifolds of the original AdS 2 x S 2 near horizon geometry. During this analysis we demonstrate that the quantum entropy function is insensitive to the details of the infrared cutoff used in the computation, and the details of the boundary terms added to the action. We also discuss the role of the asymptotic symmetries of AdS 2 in carrying out the path integral in the definition of quantum entropy function. Finally we show that even though quantum entropy function is expected to compute the absolute degeneracy in a given charge and angular momentum sector, it can also be used to compute the index. This can then be compared with the microscopic computation of the index.

Evaluation of single and multi-threshold entropy-based algorithms for folded substrate analysis

Directory of Open Access Journals (Sweden)

Magdolna Apro

2011-10-01

Full Text Available This paper presents a detailed evaluation of two variants of Maximum Entropy image segmentation algorithm(single and multi-thresholding with respect to their performance on segmenting test images showing folded substrates.The segmentation quality was determined by evaluating values of four different measures: misclassificationerror, modified Hausdorff distance, relative foreground area error and positive-negative false detection ratio. Newnormalization methods were proposed in order to combine all parameters into a unique algorithm evaluation rating.The segmentation algorithms were tested on images obtained by three different digitalisation methods coveringfour different surface textures. In addition, the methods were also tested on three images presenting a perfect fold.The obtained results showed that Multi-Maximum Entropy algorithm is better suited for the analysis of imagesshowing folded substrates.

Isolated single-molecule magnets on native gold.

Science.gov (United States)

Zobbi, Laura; Mannini, Matteo; Pacchioni, Mirko; Chastanet, Guillaume; Bonacchi, Daniele; Zanardi, Chiara; Biagi, Roberto; Del Pennino, Umberto; Gatteschi, Dante; Cornia, Andrea; Sessoli, Roberta

2005-03-28

The incorporation of thioether groups in the structure of a Mn12 single-molecule magnet, [Mn12(O12)(L)16(H2O)4] with L = 4-(methylthio)benzoate, is a successful route to the deposition of well-separated clusters on native gold surfaces and to the addressing of individual molecules by scanning tunnelling microscopy.

Atomic-Scale Control of Electron Transport through Single Molecules

DEFF Research Database (Denmark)

Wang, Y. F.; Kroger, J.; Berndt, R.

2010-01-01

Tin-phthalocyanine molecules adsorbed on Ag(111) were contacted with the tip of a cryogenic scanning tunneling microscope. Orders-of-magnitude variations of the single-molecule junction conductance were achieved by controllably dehydrogenating the molecule and by modifying the atomic structure...

Silicon photon-counting avalanche diodes for single-molecule fluorescence spectroscopy

Science.gov (United States)

Michalet, Xavier; Ingargiola, Antonino; Colyer, Ryan A.; Scalia, Giuseppe; Weiss, Shimon; Maccagnani, Piera; Gulinatti, Angelo; Rech, Ivan; Ghioni, Massimo

2014-01-01

Solution-based single-molecule fluorescence spectroscopy is a powerful experimental tool with applications in cell biology, biochemistry and biophysics. The basic feature of this technique is to excite and collect light from a very small volume and work in a low concentration regime resulting in rare burst-like events corresponding to the transit of a single molecule. Detecting photon bursts is a challenging task: the small number of emitted photons in each burst calls for high detector sensitivity. Bursts are very brief, requiring detectors with fast response time and capable of sustaining high count rates. Finally, many bursts need to be accumulated to achieve proper statistical accuracy, resulting in long measurement time unless parallelization strategies are implemented to speed up data acquisition. In this paper we will show that silicon single-photon avalanche diodes (SPADs) best meet the needs of single-molecule detection. We will review the key SPAD parameters and highlight the issues to be addressed in their design, fabrication and operation. After surveying the state-of-the-art SPAD technologies, we will describe our recent progress towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. The potential of this approach is illustrated with single-molecule Förster resonance energy transfer measurements. PMID:25309114

Single-Molecule Analysis for RISC Assembly and Target Cleavage.

Science.gov (United States)

Sasaki, Hiroshi M; Tadakuma, Hisashi; Tomari, Yukihide

2018-01-01

RNA-induced silencing complex (RISC) is a small RNA-protein complex that mediates silencing of complementary target RNAs. Biochemistry has been successfully used to characterize the molecular mechanism of RISC assembly and function for nearly two decades. However, further dissection of intermediate states during the reactions has been warranted to fill in the gaps in our understanding of RNA silencing mechanisms. Single-molecule analysis with total internal reflection fluorescence (TIRF) microscopy is a powerful imaging-based approach to interrogate complex formation and dynamics at the individual molecule level with high sensitivity. Combining this technique with our recently established in vitro reconstitution system of fly Ago2-RISC, we have developed a single-molecule observation system for RISC assembly. In this chapter, we summarize the detailed protocol for single-molecule analysis of chaperone-assisted assembly of fly Ago2-RISC as well as its target cleavage reaction.

Evaluation of the Kinetic Property of Single-Molecule Junctions by Tunneling Current Measurements.

Science.gov (United States)

Harashima, Takanori; Hasegawa, Yusuke; Kiguchi, Manabu; Nishino, Tomoaki

2018-01-01

We investigated the formation and breaking of single-molecule junctions of two kinds of dithiol molecules by time-resolved tunneling current measurements in a metal nanogap. The resulting current trajectory was statistically analyzed to determine the single-molecule conductance and, more importantly, to reveal the kinetic property of the single-molecular junction. These results suggested that combining a measurement of the single-molecule conductance and statistical analysis is a promising method to uncover the kinetic properties of the single-molecule junction.

Entropy of adsorption of mixed surfactants from solutions onto the air/water interface

Science.gov (United States)

Chen, L.-W.; Chen, J.-H.; Zhou, N.-F.

1995-01-01

The partial molar entropy change for mixed surfactant molecules adsorbed from solution at the air/water interface has been investigated by surface thermodynamics based upon the experimental surface tension isotherms at various temperatures. Results for different surfactant mixtures of sodium dodecyl sulfate and sodium tetradecyl sulfate, decylpyridinium chloride and sodium alkylsulfonates have shown that the partial molar entropy changes for adsorption of the mixed surfactants were generally negative and decreased with increasing adsorption to a minimum near the maximum adsorption and then increased abruptly. The entropy decrease can be explained by the adsorption-orientation of surfactant molecules in the adsorbed monolayer and the abrupt entropy increase at the maximum adsorption is possible due to the strong repulsion between the adsorbed molecules.

A Starting Point for Fluorescence-Based Single-Molecule Measurements in Biomolecular Research

Directory of Open Access Journals (Sweden)

Alexander Gust

2014-09-01

Full Text Available Single-molecule fluorescence techniques are ideally suited to provide information about the structure-function-dynamics relationship of a biomolecule as static and dynamic heterogeneity can be easily detected. However, what type of single-molecule fluorescence technique is suited for which kind of biological question and what are the obstacles on the way to a successful single-molecule microscopy experiment? In this review, we provide practical insights into fluorescence-based single-molecule experiments aiming for scientists who wish to take their experiments to the single-molecule level. We especially focus on fluorescence resonance energy transfer (FRET experiments as these are a widely employed tool for the investigation of biomolecular mechanisms. We will guide the reader through the most critical steps that determine the success and quality of diffusion-based confocal and immobilization-based total internal reflection fluorescence microscopy. We discuss the specific chemical and photophysical requirements that make fluorescent dyes suitable for single-molecule fluorescence experiments. Most importantly, we review recently emerged photoprotection systems as well as passivation and immobilization strategies that enable the observation of fluorescently labeled molecules under biocompatible conditions. Moreover, we discuss how the optical single-molecule toolkit has been extended in recent years to capture the physiological complexity of a cell making it even more relevant for biological research.

Infinite Shannon entropy

International Nuclear Information System (INIS)

Baccetti, Valentina; Visser, Matt

2013-01-01

Even if a probability distribution is properly normalizable, its associated Shannon (or von Neumann) entropy can easily be infinite. We carefully analyze conditions under which this phenomenon can occur. Roughly speaking, this happens when arbitrarily small amounts of probability are dispersed into an infinite number of states; we shall quantify this observation and make it precise. We develop several particularly simple, elementary, and useful bounds, and also provide some asymptotic estimates, leading to necessary and sufficient conditions for the occurrence of infinite Shannon entropy. We go to some effort to keep technical computations as simple and conceptually clear as possible. In particular, we shall see that large entropies cannot be localized in state space; large entropies can only be supported on an exponentially large number of states. We are for the time being interested in single-channel Shannon entropy in the information theoretic sense, not entropy in a stochastic field theory or quantum field theory defined over some configuration space, on the grounds that this simple problem is a necessary precursor to understanding infinite entropy in a field theoretic context. (paper)

Single molecules and single nanoparticles as windows to the nanoscale

Science.gov (United States)

Caldarola, Martín; Orrit, Michel

2018-05-01

Since the first optical detection of single molecules, they have been used as nanometersized optical sensors to explore the physical properties of materials and light-matter interaction at the nanoscale. Understanding nanoscale properties of materials is fundamental for the development of new technology that requires precise control of atoms and molecules when the quantum nature of matter cannot be ignored. In the following lines, we illustrate this journey into nanoscience with some experiments from our group.

Magnetic field modification of ultracold molecule-molecule collisions

International Nuclear Information System (INIS)

Tscherbul, T V; Suleimanov, Yu V; Aquilanti, V; Krems, R V

2009-01-01

We present an accurate quantum mechanical study of molecule-molecule collisions in the presence of a magnetic field. The work focuses on the analysis of elastic scattering and spin relaxation in collisions of O 2 ( 3 Σ g - ) molecules at cold (∼0.1 K) and ultracold (∼10 -6 K) temperatures. Our calculations show that magnetic spin relaxation in molecule-molecule collisions is extremely efficient except at magnetic fields below 1 mT. The rate constant for spin relaxation at T=0.1 K and a magnetic field of 0.1 T is found to be as large as 6.1x10 -11 cm -3 s -1 . The magnetic field dependence of elastic and inelastic scattering cross sections at ultracold temperatures is dominated by a manifold of Feshbach resonances with the density of ∼100 resonances per Tesla for collisions of molecules in the absolute ground state. This suggests that the scattering length of ultracold molecules in the absolute ground state can be effectively tuned in a very wide range of magnetic fields. Our calculations demonstrate that the number and properties of the magnetic Feshbach resonances are dramatically different for molecules in the absolute ground and excited spin states. The density of Feshbach resonances for molecule-molecule scattering in the low-field-seeking Zeeman state is reduced by a factor of 10.

Alternative types of molecule-decorated atomic chains in Au–CO–Au single-molecule junctions

Directory of Open Access Journals (Sweden)

Zoltán Balogh

2015-06-01

Full Text Available We investigate the formation and evolution of Au–CO single-molecule break junctions. The conductance histogram exhibits two distinct molecular configurations, which are further investigated by a combined statistical analysis. According to conditional histogram and correlation analysis these molecular configurations show strong anticorrelations with each other and with pure Au monoatomic junctions and atomic chains. We identify molecular precursor configurations with somewhat higher conductance, which are formed prior to single-molecule junctions. According to detailed length analysis two distinct types of molecule-affected chain-formation processes are observed, and we compare these results to former theoretical calculations considering bridge- and atop-type molecular configurations where the latter has reduced conductance due to destructive Fano interference.

SISGR: Room Temperature Single-Molecule Detection and Imaging by Stimulated Emission Microscopy

Energy Technology Data Exchange (ETDEWEB)

Xie, Xiaoliang Sunney [Harvard Univ., Cambridge, MA (United States). Dept. of Chemistry and Chemical Biology

2017-03-13

Single-molecule spectroscopy has made considerable impact on many disciplines including chemistry, physics, and biology. To date, most single-molecule spectroscopy work is accomplished by detecting fluorescence. On the other hand, many naturally occurring chromophores, such as retinal, hemoglobin and cytochromes, do not have detectable fluorescence. There is an emerging need for single-molecule spectroscopy techniques that do not require fluorescence. In the last proposal period, we have successfully demonstrated stimulated emission microscopy, single molecule absorption, and stimulated Raman microscopy based on a high-frequency modulation transfer technique. These first-of-a- kind new spectroscopy/microscopy methods tremendously improved our ability to observe molecules that fluorescence weakly, even to the limit of single molecule detection for absorption measurement. All of these methods employ two laser beams: one (pump beam) excites a single molecule to a real or virtual excited state, and the other (probe beam) monitors the absorption/emission property of the single. We extract the intensity change of the probe beam with high sensitivity by implementing a high-frequency phase-sensitive detection scheme, which offers orders of magnitude improvement in detection sensitivity over direct absorption/emission measurement. However, single molecule detection based on fluorescence or absorption is fundamentally limited due to their broad spectral response. It is important to explore other avenues in single molecule detection and imaging which provides higher molecular specificity for studying a wide variety of heterogeneous chemical and biological systems. This proposal aimed to achieve single-molecule detection sensitivity with near resonance stimulated Raman scattering (SRS) microscopy. SRS microscopy was developed in our lab as a powerful technique for imaging heterogeneous samples based on their intrinsic vibrational contrasts, which provides much higher molecular

The Nernst theorem and statistical entropy in a (1+1)-dimensional charged black hole

International Nuclear Information System (INIS)

Ren, Z.; Junfang, Z.; Lichun, Z.

2001-01-01

It was derived that the bosonic and fermionic entropies in (1+1)-dimensional charged black hole directly by using the quantum statistical method. The result is the same as the integral expression obtained by solving the wave equation approximately. Then it is obtained the statistical entropy of the black hole by integration via the improved brick-wall method, membrane model. The derived entropy satisfies the thermodynamic relation. When the radiation temperature of the black hole tends to zero, so does the entropy. It obeys Nernst theorem. So it can be taken as Planck absolute entropy

Enthalpy-Driven RNA Folding: Single-Molecule Thermodynamics of Tetraloop–Receptor Tertiary Interaction†

Science.gov (United States)

Fiore, Julie L.; Kraemer, Benedikt; Koberling, Felix; Edmann, Rainer; Nesbitt, David J.

2010-01-01

RNA folding thermodynamics are crucial for structure prediction, which requires characterization of both enthalpic and entropic contributions of tertiary motifs to conformational stability. We explore the temperature dependence of RNA folding due to the ubiquitous GAAA tetraloop–receptor docking interaction, exploiting immobilized and freely diffusing single-molecule fluorescence resonance energy transfer (smFRET) methods. The equilibrium constant for intramolecular docking is obtained as a function of temperature (T = 21–47 °C), from which a van’t Hoff analysis yields the enthalpy (ΔH°) and entropy (ΔS°) of docking. Tetraloop–receptor docking is significantly exothermic and entropically unfavorable in 1 mM MgCl2 and 100 mM NaCl, with excellent agreement between immobilized (ΔH° = −17.4 ± 1.6 kcal/mol, and ΔS° = −56.2 ± 5.4 cal mol−1 K−1) and freely diffusing (ΔH° = −17.2 ± 1.6 kcal/mol, and ΔS° = −55.9 ± 5.2 cal mol−1 K−1) species. Kinetic heterogeneity in the tetraloop–receptor construct is unaffected over the temperature range investigated, indicating a large energy barrier for interconversion between the actively docking and nondocking subpopulations. Formation of the tetraloop–receptor interaction can account for ~60% of the ΔH° and ΔS° of P4–P6 domain folding in the Tetrahymena ribozyme, suggesting that it may act as a thermodynamic clamp for the domain. Comparison of the isolated tetraloop–receptor and other tertiary folding thermodynamics supports a theme that enthalpy- versus entropy-driven folding is determined by the number of hydrogen bonding and base stacking interactions. PMID:19186984

Statistical mechanical theory of liquid entropy

International Nuclear Information System (INIS)

Wallace, D.C.

1993-01-01

The multiparticle correlation expansion for the entropy of a classical monatomic liquid is presented. This entropy expresses the physical picture in which there is no free particle motion, but rather, each atom moves within a cage formed by its neighbors. The liquid expansion, including only pair correlations, gives an excellent account of the experimental entropy of most liquid metals, of liquid argon, and the hard sphere liquid. The pair correlation entropy is well approximated by a universal function of temperature. Higher order correlation entropy, due to n-particle irreducible correlations for n≥3, is significant in only a few liquid metals, and its occurrence suggests the presence of n-body forces. When the liquid theory is applied to the study of melting, the author discovers the important classification of normal and anomalous melting, according to whether there is not or is a significant change in the electronic structure upon melting, and he discovers the universal disordering entropy for melting of a monatomic crystal. Interesting directions for future research are: extension to include orientational correlations of molecules, theoretical calculation of the entropy of water, application to the entropy of the amorphous state, and correlational entropy of compressed argon. The author clarifies the relation among different entropy expansions in the recent literature

Single-molecule analysis of DNA replication in Xenopus egg extracts

NARCIS (Netherlands)

Yardimci, Hasan; Loveland, Anna B.; van Oijen, Antoine M.; Walter, Johannes C.; Mechali, Marcel

The recent advent in single-molecule imaging and manipulation methods has made a significant impact on the understanding of molecular mechanisms underlying many essential cellular processes. Single-molecule techniques such as electron microscopy and DNA fiber assays have been employed to study the

Single Molecule Spectroscopy on Photosynthetic Pigment-Protein Complexes

CERN Document Server

Jelezko, F; Schuler, S; Thews, E; Tietz, C; Wechsler, A; Wrachtrup, J

2001-01-01

Single molecule spectroscopy was applied to unravel the energy transfer pathway in photosynthetic pigment-protein complexes. Detailed analysis of excitation and fluorescence emission spectra has been made for peripheral plant antenna LHC II and Photosystem I from cyanobacterium Synechococcus elongatus. Optical transitions of individual pigments were resolved under nonselective excitation of antenna chlorophylls. High-resolution fluorescence spectroscopy of individual plant antenna LHC II indicates that at low temperatures, the excitation energy is localized on the red-most Chl a pool absorbing at 680 nm. More than one pigment molecule is responsible for the fluorescence emission of the LHC II trimer. The spectral lines of single Chl a molecules absorbing at 675 nm are broadened because of the Foerster energy transfer towards the red-most pigments. Low-temperature spectroscopy on single PS I trimers indicates that two subgroups of pigments, which are present in the red antenna pool, differ by the strength of t...

Single-Molecule Interfacial Electron Transfer

Energy Technology Data Exchange (ETDEWEB)

Ho, Wilson [Univ. of California, Irvine, CA (United States)

2018-02-03

Interfacial electron transfer (ET) plays an important role in many chemical and biological processes. Specifically, interfacial ET in TiO₂-based systems is important to solar energy technology, catalysis, and environmental remediation technology. However, the microscopic mechanism of interfacial ET is not well understood with regard to atomic surface structure, molecular structure, bonding, orientation, and motion. In this project, we used two complementary methodologies; single-molecule fluorescence spectroscopy, and scanning-tunneling microscopy and spectroscopy (STM and STS) to address this scientific need. The goal of this project was to integrate these techniques and measure the molecular dependence of ET between adsorbed molecules and TiO₂ semiconductor surfaces and the ET induced reactions such as the splitting of water. The scanning probe techniques, STM and STS, are capable of providing the highest spatial resolution but not easily time-resolved data. Single-molecule fluorescence spectroscopy is capable of good time resolution but requires further development to match the spatial resolution of the STM. The integrated approach involving Peter Lu at Bowling Green State University (BGSU) and Wilson Ho at the University of California, Irvine (UC Irvine) produced methods for time and spatially resolved chemical imaging of interfacial electron transfer dynamics and photocatalytic reactions. An integral aspect of the joint research was a significant exchange of graduate students to work at the two institutions. This project bridged complementary approaches to investigate a set of common problems by working with the same molecules on a variety of solid surfaces, but using appropriate techniques to probe under ambient (BGSU) and ultrahigh vacuum (UCI) conditions. The molecular level understanding of the fundamental interfacial electron transfer processes obtained in this joint project will be important for developing efficient light harvesting

Metal-Controlled Magnetoresistance at Room Temperature in Single-Molecule Devices.

Science.gov (United States)

Aragonès, Albert C; Aravena, Daniel; Valverde-Muñoz, Francisco J; Real, José Antonio; Sanz, Fausto; Díez-Pérez, Ismael; Ruiz, Eliseo

2017-04-26

The appropriate choice of the transition metal complex and metal surface electronic structure opens the possibility to control the spin of the charge carriers through the resulting hybrid molecule/metal spinterface in a single-molecule electrical contact at room temperature. The single-molecule conductance of a Au/molecule/Ni junction can be switched by flipping the magnetization direction of the ferromagnetic electrode. The requirements of the molecule include not just the presence of unpaired electrons: the electronic configuration of the metal center has to provide occupied or empty orbitals that strongly interact with the junction metal electrodes and that are close in energy to their Fermi levels for one of the electronic spins only. The key ingredient for the metal surface is to provide an efficient spin texture induced by the spin-orbit coupling in the topological surface states that results in an efficient spin-dependent interaction with the orbitals of the molecule. The strong magnetoresistance effect found in this kind of single-molecule wire opens a new approach for the design of room-temperature nanoscale devices based on spin-polarized currents controlled at molecular level.

Single-Molecule Chemistry with Surface- and Tip-Enhanced Raman Spectroscopy.

Science.gov (United States)

Zrimsek, Alyssa B; Chiang, Naihao; Mattei, Michael; Zaleski, Stephanie; McAnally, Michael O; Chapman, Craig T; Henry, Anne-Isabelle; Schatz, George C; Van Duyne, Richard P

2017-06-14

Single-molecule (SM) surface-enhanced Raman spectroscopy (SERS) and tip-enhanced Raman spectroscopy (TERS) have emerged as analytical techniques for characterizing molecular systems in nanoscale environments. SERS and TERS use plasmonically enhanced Raman scattering to characterize the chemical information on single molecules. Additionally, TERS can image single molecules with subnanometer spatial resolution. In this review, we cover the development and history of SERS and TERS, including the concept of SERS hot spots and the plasmonic nanostructures necessary for SM detection, the past and current methodologies for verifying SMSERS, and investigations into understanding the signal heterogeneities observed with SMSERS. Moving on to TERS, we cover tip fabrication and the physical origins of the subnanometer spatial resolution. Then, we highlight recent advances of SMSERS and TERS in fields such as electrochemistry, catalysis, and SM electronics, which all benefit from the vibrational characterization of single molecules. SMSERS and TERS provide new insights on molecular behavior that would otherwise be obscured in an ensemble-averaged measurement.

A New Theoretical Approach to Single-Molecule Fluorescence Optical Studies of RNA Dynamics

International Nuclear Information System (INIS)

Zhao Xinghai; Shan Guangcun; Bao Shuying

2011-01-01

Single-molecule fluorescence spectroscopy in condensed phases has many important chemical and biological applications. The single-molecule fluorescence measurements contain information about conformational dynamics on a vast range of time scales. Based on the data analysis protocols methodology proposed by X. Sunney Xie, the theoretical study here mainly focuses on the single-molecule studies of single RNA with interconversions among different conformational states, to with a single FRET pair attached. We obtain analytical expressions for fluorescence lifetime correlation functions that relate changes in fluorescence lifetime to the distance-dependent FRET mechanism within the context of the Smoluchowski diffusion model. The present work establishes useful guideline for the single-molecule studies of biomolecules to reveal the complicated folding dynamics of single RNA molecules at nanometer scale.

Nonlinear and Nonsymmetric Single-Molecule Electronic Properties Towards Molecular Information Processing.

Science.gov (United States)

Tamaki, Takashi; Ogawa, Takuji

2017-09-05

This review highlights molecular design for nonlinear and nonsymmetric single-molecule electronic properties such as rectification, negative differential resistance, and switching, which are important components of future single-molecule information processing devices. Perspectives on integrated "molecular circuits" are also provided. Nonlinear and nonsymmetric single-molecule electronics can be designed by utilizing (1) asymmetric molecular cores, (2) asymmetric anchoring groups, (3) an asymmetric junction environment, and (4) asymmetric electrode materials. This review mainly focuses on the design of molecular cores.

Estimating single molecule conductance from spontaneous evolution of a molecular contact

Science.gov (United States)

Gil, M.; Malinowski, T.; Iazykov, M.; Klein, H. R.

2018-03-01

We present an original method to estimate the conductivity of a single molecule anchored to nanometric-sized metallic electrodes, using a Mechanically Controlled Break Junction operated at room temperature in the liquid. We record the conductance through the metal/molecules/metal nanocontact while keeping the metallic electrodes at a fixed distance. Taking advantage of thermal diffusion and electromigration, we let the contact naturally explore the more stable configurations around a chosen conductance value. The conductance of a single molecule is estimated from a statistical analysis of raw conductance and conductance standard deviation data for molecular contacts containing up to 14 molecules. The single molecule conductance values are interpreted as time-averaged conductance of an ensemble of conformers at thermal equilibrium.

Single-Molecule Light-Sheet Imaging of Suspended T Cells.

Science.gov (United States)

Ponjavic, Aleks; McColl, James; Carr, Alexander R; Santos, Ana Mafalda; Kulenkampff, Klara; Lippert, Anna; Davis, Simon J; Klenerman, David; Lee, Steven F

2018-05-08

Adaptive immune responses are initiated by triggering of the T cell receptor. Single-molecule imaging based on total internal reflection fluorescence microscopy at coverslip/basal cell interfaces is commonly used to study this process. These experiments have suggested, unexpectedly, that the diffusional behavior and organization of signaling proteins and receptors may be constrained before activation. However, it is unclear to what extent the molecular behavior and cell state is affected by the imaging conditions, i.e., by the presence of a supporting surface. In this study, we implemented single-molecule light-sheet microscopy, which enables single receptors to be directly visualized at any plane in a cell to study protein dynamics and organization in live, resting T cells. The light sheet enabled the acquisition of high-quality single-molecule fluorescence images that were comparable to those of total internal reflection fluorescence microscopy. By comparing the apical and basal surfaces of surface-contacting T cells using single-molecule light-sheet microscopy, we found that most coated-glass surfaces and supported lipid bilayers profoundly affected the diffusion of membrane proteins (T cell receptor and CD45) and that all the surfaces induced calcium influx to various degrees. Our results suggest that, when studying resting T cells, surfaces are best avoided, which we achieve here by suspending cells in agarose. Copyright © 2018. Published by Elsevier Inc.

Graphical models for inferring single molecule dynamics

Directory of Open Access Journals (Sweden)

Gonzalez Ruben L

2010-10-01

Full Text Available Abstract Background The recent explosion of experimental techniques in single molecule biophysics has generated a variety of novel time series data requiring equally novel computational tools for analysis and inference. This article describes in general terms how graphical modeling may be used to learn from biophysical time series data using the variational Bayesian expectation maximization algorithm (VBEM. The discussion is illustrated by the example of single-molecule fluorescence resonance energy transfer (smFRET versus time data, where the smFRET time series is modeled as a hidden Markov model (HMM with Gaussian observables. A detailed description of smFRET is provided as well. Results The VBEM algorithm returns the model’s evidence and an approximating posterior parameter distribution given the data. The former provides a metric for model selection via maximum evidence (ME, and the latter a description of the model’s parameters learned from the data. ME/VBEM provide several advantages over the more commonly used approach of maximum likelihood (ML optimized by the expectation maximization (EM algorithm, the most important being a natural form of model selection and a well-posed (non-divergent optimization problem. Conclusions The results demonstrate the utility of graphical modeling for inference of dynamic processes in single molecule biophysics.

Deep learning for single-molecule science

Science.gov (United States)

Albrecht, Tim; Slabaugh, Gregory; Alonso, Eduardo; Al-Arif, SM Masudur R.

2017-10-01

Exploring and making predictions based on single-molecule data can be challenging, not only due to the sheer size of the datasets, but also because a priori knowledge about the signal characteristics is typically limited and poor signal-to-noise ratio. For example, hypothesis-driven data exploration, informed by an expectation of the signal characteristics, can lead to interpretation bias or loss of information. Equally, even when the different data categories are known, e.g., the four bases in DNA sequencing, it is often difficult to know how to make best use of the available information content. The latest developments in machine learning (ML), so-called deep learning (DL) offer interesting, new avenues to address such challenges. In some applications, such as speech and image recognition, DL has been able to outperform conventional ML strategies and even human performance. However, to date DL has not been applied much in single-molecule science, presumably in part because relatively little is known about the ‘internal workings’ of such DL tools within single-molecule science as a field. In this Tutorial, we make an attempt to illustrate in a step-by-step guide how one of those, a convolutional neural network (CNN), may be used for base calling in DNA sequencing applications. We compare it with a SVM as a more conventional ML method, and discuss some of the strengths and weaknesses of the approach. In particular, a ‘deep’ neural network has many features of a ‘black box’, which has important implications on how we look at and interpret data.

Vibrationally coupled electron transport through single-molecule junctions

Energy Technology Data Exchange (ETDEWEB)

Haertle, Rainer

2012-04-26

Single-molecule junctions are among the smallest electric circuits. They consist of a molecule that is bound to a left and a right electrode. With such a molecular nanocontact, the flow of electrical currents through a single molecule can be studied and controlled. Experiments on single-molecule junctions show that a single molecule carries electrical currents that can even be in the microampere regime. Thereby, a number of transport phenomena have been observed, such as, for example, diode- or transistor-like behavior, negative differential resistance and conductance switching. An objective of this field, which is commonly referred to as molecular electronics, is to relate these transport phenomena to the properties of the molecule in the contact. To this end, theoretical model calculations are employed, which facilitate an understanding of the underlying transport processes and mechanisms. Thereby, one has to take into account that molecules are flexible structures, which respond to a change of their charge state by a profound reorganization of their geometrical structure or may even dissociate. It is thus important to understand the interrelation between the vibrational degrees of freedom of a singlemolecule junction and the electrical current flowing through the contact. In this thesis, we investigate vibrational effects in electron transport through singlemolecule junctions. For these studies, we calculate and analyze transport characteristics of both generic and first-principles based model systems of a molecular contact. To this end, we employ a master equation and a nonequilibrium Green's function approach. Both methods are suitable to describe this nonequilibrium transport problem and treat the interactions of the tunneling electrons on the molecular bridge non-perturbatively. This is particularly important with respect to the vibrational degrees of freedom, which may strongly interact with the tunneling electrons. We show in detail that the resulting

Repurposing a Benchtop Centrifuge for High-Throughput Single-Molecule Force Spectroscopy.

Science.gov (United States)

Yang, Darren; Wong, Wesley P

2018-01-01

We present high-throughput single-molecule manipulation using a benchtop centrifuge, overcoming limitations common in other single-molecule approaches such as high cost, low throughput, technical difficulty, and strict infrastructure requirements. An inexpensive and compact Centrifuge Force Microscope (CFM) adapted to a commercial centrifuge enables use by nonspecialists, and integration with DNA nanoswitches facilitates both reliable measurements and repeated molecular interrogation. Here, we provide detailed protocols for constructing the CFM, creating DNA nanoswitch samples, and carrying out single-molecule force measurements.

Connecting diffusion and entropy of bulk water at the single particle ...

Indian Academy of Sciences (India)

DEBASIS SAHA

Sex. The excess entropy denotes the difference between the actual entropy of the system and the system's entropy if it behaves as ... as viscosity or self-diffusion coefficient as well as the ..... modynamic determination of fragility in liquids and a.

Spectrally Resolved and Functional Super-resolution Microscopy via Ultrahigh-Throughput Single-Molecule Spectroscopy.

Science.gov (United States)

Yan, Rui; Moon, Seonah; Kenny, Samuel J; Xu, Ke

2018-03-20

As an elegant integration of the spatial and temporal dimensions of single-molecule fluorescence, single-molecule localization microscopy (SMLM) overcomes the diffraction-limited resolution barrier of optical microscopy by localizing single molecules that stochastically switch between fluorescent and dark states over time. While this type of super-resolution microscopy (SRM) technique readily achieves remarkable spatial resolutions of ∼10 nm, it typically provides no spectral information. Meanwhile, current scanning-based single-location approaches for mapping the positions and spectra of single molecules are limited by low throughput and are difficult to apply to densely labeled (bio)samples. In this Account, we summarize the rationale, design, and results of our recent efforts toward the integration of the spectral dimension of single-molecule fluorescence with SMLM to achieve spectrally resolved SMLM (SR-SMLM) and functional SRM ( f-SRM). By developing a wide-field scheme for spectral measurement and implementing single-molecule fluorescence on-off switching typical of SMLM, we first showed that in densely labeled (bio)samples it is possible to record the fluorescence spectra and positions of millions of single molecules synchronously within minutes, giving rise to ultrahigh-throughput single-molecule spectroscopy and SR-SMLM. This allowed us to first show statistically that for many dyes, single molecules of the same species exhibit near identical emission in fixed cells. This narrow distribution of emission wavelengths, which contrasts markedly with previous results at solid surfaces, allowed us to unambiguously identify single molecules of spectrally similar dyes. Crosstalk-free, multiplexed SRM was thus achieved for four dyes that were merely 10 nm apart in emission spectrum, with the three-dimensional SRM images of all four dyes being automatically aligned within one image channel. The ability to incorporate single-molecule fluorescence measurement with

Carnot to Clausius: Caloric to Entropy

Science.gov (United States)

Newburgh, Ronald

2009-01-01

This paper discusses how the Carnot engine led to the formulation of the second law of thermodynamics and entropy. The operation of the engine is analysed both in terms of heat as the caloric fluid and heat as a form of energy. A keystone of Carnot's thinking was the absolute conservation of caloric. Although the Carnot analysis was partly…

Real-time single-molecule imaging of quantum interference.

Science.gov (United States)

Juffmann, Thomas; Milic, Adriana; Müllneritsch, Michael; Asenbaum, Peter; Tsukernik, Alexander; Tüxen, Jens; Mayor, Marcel; Cheshnovsky, Ori; Arndt, Markus

2012-03-25

The observation of interference patterns in double-slit experiments with massive particles is generally regarded as the ultimate demonstration of the quantum nature of these objects. Such matter-wave interference has been observed for electrons, neutrons, atoms and molecules and, in contrast to classical physics, quantum interference can be observed when single particles arrive at the detector one by one. The build-up of such patterns in experiments with electrons has been described as the "most beautiful experiment in physics". Here, we show how a combination of nanofabrication and nano-imaging allows us to record the full two-dimensional build-up of quantum interference patterns in real time for phthalocyanine molecules and for derivatives of phthalocyanine molecules, which have masses of 514 AMU and 1,298 AMU respectively. A laser-controlled micro-evaporation source was used to produce a beam of molecules with the required intensity and coherence, and the gratings were machined in 10-nm-thick silicon nitride membranes to reduce the effect of van der Waals forces. Wide-field fluorescence microscopy detected the position of each molecule with an accuracy of 10 nm and revealed the build-up of a deterministic ensemble interference pattern from single molecules that arrived stochastically at the detector. In addition to providing this particularly clear demonstration of wave-particle duality, our approach could also be used to study larger molecules and explore the boundary between quantum and classical physics.

Single-molecule chemical reactions on DNA origami

DEFF Research Database (Denmark)

Voigt, Niels Vinther; Tørring, Thomas; Rotaru, Alexandru

2010-01-01

as templates for building materials with new functional properties. Relatively large nanocomponents such as nanoparticles and biomolecules can also be integrated into DNA nanostructures and imaged. Here, we show that chemical reactions with single molecules can be performed and imaged at a local position...... on a DNA origami scaffold by atomic force microscopy. The high yields and chemoselectivities of successive cleavage and bond-forming reactions observed in these experiments demonstrate the feasibility of post-assembly chemical modification of DNA nanostructures and their potential use as locally......DNA nanotechnology and particularly DNA origami, in which long, single-stranded DNA molecules are folded into predetermined shapes, can be used to form complex self-assembled nanostructures. Although DNA itself has limited chemical, optical or electronic functionality, DNA nanostructures can serve...

Development of new photon-counting detectors for single-molecule fluorescence microscopy

Science.gov (United States)

Michalet, X.; Colyer, R. A.; Scalia, G.; Ingargiola, A.; Lin, R.; Millaud, J. E.; Weiss, S.; Siegmund, Oswald H. W.; Tremsin, Anton S.; Vallerga, John V.; Cheng, A.; Levi, M.; Aharoni, D.; Arisaka, K.; Villa, F.; Guerrieri, F.; Panzeri, F.; Rech, I.; Gulinatti, A.; Zappa, F.; Ghioni, M.; Cova, S.

2013-01-01

Two optical configurations are commonly used in single-molecule fluorescence microscopy: point-like excitation and detection to study freely diffusing molecules, and wide field illumination and detection to study surface immobilized or slowly diffusing molecules. Both approaches have common features, but also differ in significant aspects. In particular, they use different detectors, which share some requirements but also have major technical differences. Currently, two types of detectors best fulfil the needs of each approach: single-photon-counting avalanche diodes (SPADs) for point-like detection, and electron-multiplying charge-coupled devices (EMCCDs) for wide field detection. However, there is room for improvements in both cases. The first configuration suffers from low throughput owing to the analysis of data from a single location. The second, on the other hand, is limited to relatively low frame rates and loses the benefit of single-photon-counting approaches. During the past few years, new developments in point-like and wide field detectors have started addressing some of these issues. Here, we describe our recent progresses towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. We also discuss our development of large area photon-counting cameras achieving subnanosecond resolution for fluorescence lifetime imaging applications at the single-molecule level. PMID:23267185

Molecular spintronics using single-molecule magnets

Science.gov (United States)

Bogani, Lapo; Wernsdorfer, Wolfgang

2008-03-01

A revolution in electronics is in view, with the contemporary evolution of the two novel disciplines of spintronics and molecular electronics. A fundamental link between these two fields can be established using molecular magnetic materials and, in particular, single-molecule magnets. Here, we review the first progress in the resulting field, molecular spintronics, which will enable the manipulation of spin and charges in electronic devices containing one or more molecules. We discuss the advantages over more conventional materials, and the potential applications in information storage and processing. We also outline current challenges in the field, and propose convenient schemes to overcome them.

Modulation of intermolecular interactions in single-molecule magnets

Science.gov (United States)

Heroux, Katie Jeanne

Polynuclear manganese clusters exhibiting interesting magnetic and quantum properties have been an area of intense research since the discovery of the first single-molecule magnet (SMM) in 1993. These molecules, below their blocking temperature, function as single-domain magnetic particles which exhibit classical macroscale magnetic properties as well as quantum mechanical phenomena such as quantum tunnelling of magnetization (QTM) and quantum phase interference. The union of classical and quantum behavior in these nanomaterials makes SMMs ideal candidates for high-density information storage and quantum computing. However, environmental coupling factors (nuclear spins, phonons, neighboring molecules) must be minimized if such applications are ever to be fully realized. The focus of this work is making small structural changes in well-known manganese SMMs in order to drastically enhance the overall magnetic and quantum properties of the system. Well-isolated molecules of high crystalline quality should lead to well-defined energetic and spectral properties as well. An advantage of SMMs over bulk magnetic materials is that they can be chemically altered from a "bottom-up" approach providing a synthetic tool for tuning magnetic properties. This systematic approach is utilized in the work presented herein by incorporating bulky ligands and/or counterions to "isolate" the magnetic core of [Mn4] dicubane SMMs. Reducing intermolecular interactions in the crystal lattice (neighboring molecules, solvate molecules, dipolar interactions) is an important step toward developing viable quantum computing devices. Detailed bulk magnetic studies as well as single crystal magnetization hysteresis and high-frequency EPR studies on these sterically-isolated complexes show enhanced, and sometimes even unexpected, quantum dynamics. The importance of intra- and intermolecular interactions remains a common theme throughout this work, extending to other SMMs of various topology including

Towards single molecule biosensors using super-resolution fluorescence microscopy.

Science.gov (United States)

Lu, Xun; Nicovich, Philip R; Gaus, Katharina; Gooding, J Justin

2017-07-15

Conventional immunosensors require many binding events to give a single transducer output which represents the concentration of the analyte in the sample. Because of the requirements to selectively detect species in complex samples, immunosensing interfaces must allow immobilisation of antibodies while repelling nonspecific adsorption of other species. These requirements lead to quite sophisticated interfacial design, often with molecular level control, but we have no tools to characterise how well these interfaces work at the molecular level. The work reported herein is an initial feasibility study to show that antibody-antigen binding events can be monitored at the single molecule level using single molecule localisation microscopy (SMLM). The steps to achieve this first requires showing that indium tin oxide surfaces can be used for SMLM, then that these surfaces can be modified with self-assembled monolayers using organophosphonic acid derivatives, that the amount of antigens and antibodies on the surface can be controlled and monitored at the single molecule level and finally antibody binding to antigen modified surfaces can be monitored. The results show the amount of antibody that binds to an antigen modified surface is dependent on both the concentration of antigen on the surface and the concentration of antibody in solution. This study demonstrates the potential of SMLM for characterising biosensing interfaces and as the transducer in a massively parallel, wide field, single molecule detection scheme for quantitative analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrochemical Single-Molecule Transistors with Optimized Gate Coupling

DEFF Research Database (Denmark)

Osorio, Henrry M.; Catarelli, Samantha; Cea, Pilar

2015-01-01

Electrochemical gating at the single molecule level of viologen molecular bridges in ionic liquids is examined. Contrary to previous data recorded in aqueous electrolytes, a clear and sharp peak in the single molecule conductance versus electrochemical potential data is obtained in ionic liquids....... These data are rationalized in terms of a two-step electrochemical model for charge transport across the redox bridge. In this model the gate coupling in the ionic liquid is found to be fully effective with a modeled gate coupling parameter, ξ, of unity. This compares to a much lower gate coupling parameter...

Single-molecule fluorescence microscopy review: shedding new light on old problems.

Science.gov (United States)

Shashkova, Sviatlana; Leake, Mark C

2017-08-31

Fluorescence microscopy is an invaluable tool in the biosciences, a genuine workhorse technique offering exceptional contrast in conjunction with high specificity of labelling with relatively minimal perturbation to biological samples compared with many competing biophysical techniques. Improvements in detector and dye technologies coupled to advances in image analysis methods have fuelled recent development towards single-molecule fluorescence microscopy, which can utilize light microscopy tools to enable the faithful detection and analysis of single fluorescent molecules used as reporter tags in biological samples. For example, the discovery of GFP, initiating the so-called 'green revolution', has pushed experimental tools in the biosciences to a completely new level of functional imaging of living samples, culminating in single fluorescent protein molecule detection. Today, fluorescence microscopy is an indispensable tool in single-molecule investigations, providing a high signal-to-noise ratio for visualization while still retaining the key features in the physiological context of native biological systems. In this review, we discuss some of the recent discoveries in the life sciences which have been enabled using single-molecule fluorescence microscopy, paying particular attention to the so-called 'super-resolution' fluorescence microscopy techniques in live cells, which are at the cutting-edge of these methods. In particular, how these tools can reveal new insights into long-standing puzzles in biology: old problems, which have been impossible to tackle using other more traditional tools until the emergence of new single-molecule fluorescence microscopy techniques. © 2017 The Author(s).

Investigation of photobleaching and saturation of single molecules by fluorophore recrossing events

Energy Technology Data Exchange (ETDEWEB)

Burrows, Sean M.; Reif, Randall D. [Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061 (United States); Pappas, Dimitri [Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061 (United States)], E-mail: d.pappas@ttu.edu

2007-08-15

A method for investigation of photobleaching and saturation of single molecules by fluorophore recrossing events in a laser beam is described. The diffraction-limited probe volumes encountered in single-molecule detection (SMD) produce high excitation irradiance, which can decrease available signal. The single molecules of several dyes were detected and the data was used to extract interpeak times above a defined threshold value. The interpeak times revealed the number of fluorophore recrossing events. The number of molecules detected that were within 2 ms of each other represented a molecular recrossing for this work. Calcein, fluorescein and R-phycoerythrin were analyzed and the saturation irradiance and photobleaching effects were determined as a function of irradiance. This approach is simple and it serves as a method of optimizing experimental conditions for single-molecule detection.

Total Internal Reflection Fluorescence Microscopy Imaging-Guided Confocal Single-Molecule Fluorescence Spectroscopy

OpenAIRE

Zheng, Desheng; Kaldaras, Leonora; Lu, H. Peter

2013-01-01

We have developed an integrated spectroscopy system combining total internal reflection fluorescence microscopy imaging with confocal single-molecule fluorescence spectroscopy for two-dimensional interfaces. This spectroscopy approach is capable of both multiple molecules simultaneously sampling and in situ confocal fluorescence dynamics analyses of individual molecules of interest. We have demonstrated the calibration with fluorescent microspheres, and carried out single-molecule spectroscop...

Functionalized single walled carbon nanotubes as template for water storage device

Energy Technology Data Exchange (ETDEWEB)

Paul, Sanjib; Taraphder, Srabani, E-mail: srabani@chem.iitkgp.ernet.in

2016-11-10

Single walled carbon nanotubes, endohedrally functionalized with a protonated/unprotonated carboxylic acid group, are examined as potential templates for water storage using classical molecular dynamics simulation studies. Following a spontaneous entry of water molecules into the core of model functionalized carbon nanotubes (FCNTs), a large fraction of water molecules are found to be trapped inside FCNTs of lengths 50 and 100 Å. Only water molecules near the two open ends of the nanotube are exchanged with the bulk solvent. The residence times of water molecules inside FCNTs are investigated by varying the length of the tube, the length of suspended functional group and the protonation state of the carboxylic acid group. Favorable energetic interactions between the functional group and water, assisted by a substantial gain in rotational entropy, are found to compensate for the entropy loss resulting from restricted translational diffusion of trapped water molecules.

DNA analysis by single molecule stretching in nanofluidic biochips

DEFF Research Database (Denmark)

Abad, E.; Juarros, A.; Retolaza, A.

2011-01-01

Imprint Lithography (NIL) technology combined with a conventional anodic bonding of the silicon base and Pyrex cover. Using this chip, we have performed single molecule imaging on a bench-top fluorescent microscope system. Lambda phage DNA was used as a model sample to characterize the chip. Single molecules of λ-DNA......Stretching single DNA molecules by confinement in nanofluidic channels has attracted a great interest during the last few years as a DNA analysis tool. We have designed and fabricated a sealed micro/nanofluidic device for DNA stretching applications, based on the use of the high throughput Nano...... stained with the fluorescent dye YOYO-1 were stretched in the nanochannel array and the experimental results were analysed to determine the extension factor of the DNA in the chip and the geometrical average of the nanochannel inner diameter. The determination of the extension ratio of the chip provides...

Synthesis of a single phase of high-entropy Laves intermetallics in the Ti-Zr-V-Cr-Ni equiatomic alloy

Science.gov (United States)

Yadav, T. P.; Mukhopadhyay, Semanti; Mishra, S. S.; Mukhopadhyay, N. K.; Srivastava, O. N.

2017-12-01

The high-entropy Ti-Zr-V-Cr-Ni (20 at% each) alloy consisting of all five hydride-forming elements was successfully synthesised by the conventional melting and casting as well as by the melt-spinning technique. The as-cast alloy consists entirely of the micron size hexagonal Laves Phase of C14 type; whereas, the melt-spun ribbon exhibits the evolution of nanocrystalline Laves phase. There was no evidence of any amorphous or any other metastable phases in the present processing condition. This is the first report of synthesising a single phase of high-entropy complex intermetallic compound in the equiatomic quinary alloy system. The detailed characterisation by X-ray diffraction, scanning and transmission electron microscopy and energy-dispersive X-ray spectroscopy confirmed the existence of a single-phase multi-component hexagonal C14-type Laves phase in all the as-cast, melt-spun and annealed alloys. The lattice parameter a = 5.08 Å and c = 8.41 Å was determined from the annealed material (annealing at 1173 K). The thermodynamic calculations following the Miedema's approach support the stability of the high-entropy multi-component Laves phase compared to that of the solid solution or glassy phases. The high hardness value (8.92 GPa at 25 g load) has been observed in nanocrystalline high-entropy alloy ribbon without any cracking. It implies that high-yield strength ( 3.00 GPa) and the reasonable fracture toughness can be achieved in this high-entropy material.

Absolute fragmentation cross sections in atom-molecule collisions: Scaling laws for non-statistical fragmentation of polycyclic aromatic hydrocarbon molecules

Energy Technology Data Exchange (ETDEWEB)

Chen, T.; Gatchell, M.; Stockett, M. H.; Alexander, J. D.; Schmidt, H. T.; Cederquist, H.; Zettergren, H., E-mail: henning@fysik.su.se [Department of Physics, Stockholm University, S-106 91 Stockholm (Sweden); Zhang, Y. [Department of Mathematics, Faculty of Physics, M. V. Lomonosov Moscow State University, Leninskie Gory, 119991 Moscow (Russian Federation); Rousseau, P.; Maclot, S.; Delaunay, R.; Adoui, L. [CIMAP, UMR 6252, CEA/CNRS/ENSICAEN/Université de Caen Basse-Normandie, bd Henri Becquerel, BP 5133, F-14070 Caen Cedex 05 (France); Université de Caen Basse-Normandie, Esplanade de la Paix, F-14032 Caen (France); Domaracka, A.; Huber, B. A. [CIMAP, UMR 6252, CEA/CNRS/ENSICAEN/Université de Caen Basse-Normandie, bd Henri Becquerel, BP 5133, F-14070 Caen Cedex 05 (France); Schlathölter, T. [Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747AG Groningen (Netherlands)

2014-06-14

We present scaling laws for absolute cross sections for non-statistical fragmentation in collisions between Polycyclic Aromatic Hydrocarbons (PAH/PAH{sup +}) and hydrogen or helium atoms with kinetic energies ranging from 50 eV to 10 keV. Further, we calculate the total fragmentation cross sections (including statistical fragmentation) for 110 eV PAH/PAH{sup +} + He collisions, and show that they compare well with experimental results. We demonstrate that non-statistical fragmentation becomes dominant for large PAHs and that it yields highly reactive fragments forming strong covalent bonds with atoms (H and N) and molecules (C{sub 6}H{sub 5}). Thus nonstatistical fragmentation may be an effective initial step in the formation of, e.g., Polycyclic Aromatic Nitrogen Heterocycles (PANHs). This relates to recent discussions on the evolution of PAHNs in space and the reactivities of defect graphene structures.

Rotating Wigner molecules and spin-related behaviors in quantum rings

International Nuclear Information System (INIS)

Yang Ning; Zhu Jialin; Dai Zhensheng

2008-01-01

The trial wavefunctions for few-electron quantum rings are presented to describe the spin-dependent rotating Wigner molecule states. The wavefunctions are constructed from the single-particle orbits which contain two variational parameters to describe the shape and size dependence of electron localization in the ring-like confinement. They can explicitly show the size dependence of single-particle orbital occupation to give an understanding of the spin rules of ground states without magnetic fields. They can also correctly describe the spin and angular momentum transitions in magnetic fields. By examining the von Neumann entropy, it is demonstrated that the wavefunctions can illustrate the entanglement between electrons in quantum rings, including the AB oscillations as well as the spin and size dependence of the entropy. Such trial wavefunctions will be useful in investigating spin-related quantum behaviors of a few electrons in quantum rings

DNA-Based Single-Molecule Electronics: From Concept to Function

Science.gov (United States)

2018-01-01

Beyond being the repository of genetic information, DNA is playing an increasingly important role as a building block for molecular electronics. Its inherent structural and molecular recognition properties render it a leading candidate for molecular electronics applications. The structural stability, diversity and programmability of DNA provide overwhelming freedom for the design and fabrication of molecular-scale devices. In the past two decades DNA has therefore attracted inordinate amounts of attention in molecular electronics. This review gives a brief survey of recent experimental progress in DNA-based single-molecule electronics with special focus on single-molecule conductance and I–V characteristics of individual DNA molecules. Existing challenges and exciting future opportunities are also discussed. PMID:29342091

DNA-Based Single-Molecule Electronics: From Concept to Function.

Science.gov (United States)

Wang, Kun

2018-01-17

Beyond being the repository of genetic information, DNA is playing an increasingly important role as a building block for molecular electronics. Its inherent structural and molecular recognition properties render it a leading candidate for molecular electronics applications. The structural stability, diversity and programmability of DNA provide overwhelming freedom for the design and fabrication of molecular-scale devices. In the past two decades DNA has therefore attracted inordinate amounts of attention in molecular electronics. This review gives a brief survey of recent experimental progress in DNA-based single-molecule electronics with special focus on single-molecule conductance and I-V characteristics of individual DNA molecules. Existing challenges and exciting future opportunities are also discussed.

DNA origami as biocompatible surface to match single-molecule and ensemble experiments

Science.gov (United States)

Gietl, Andreas; Holzmeister, Phil; Grohmann, Dina; Tinnefeld, Philip

2012-01-01

Single-molecule experiments on immobilized molecules allow unique insights into the dynamics of molecular machines and enzymes as well as their interactions. The immobilization, however, can invoke perturbation to the activity of biomolecules causing incongruities between single molecule and ensemble measurements. Here we introduce the recently developed DNA origami as a platform to transfer ensemble assays to the immobilized single molecule level without changing the nano-environment of the biomolecules. The idea is a stepwise transfer of common functional assays first to the surface of a DNA origami, which can be checked at the ensemble level, and then to the microscope glass slide for single-molecule inquiry using the DNA origami as a transfer platform. We studied the structural flexibility of a DNA Holliday junction and the TATA-binding protein (TBP)-induced bending of DNA both on freely diffusing molecules and attached to the origami structure by fluorescence resonance energy transfer. This resulted in highly congruent data sets demonstrating that the DNA origami does not influence the functionality of the biomolecule. Single-molecule data collected from surface-immobilized biomolecule-loaded DNA origami are in very good agreement with data from solution measurements supporting the fact that the DNA origami can be used as biocompatible surface in many fluorescence-based measurements. PMID:22523083

Single-molecule conductivity of non-redox and redox molecules at pure and gold-mined Au(111)-electrode surfaces

DEFF Research Database (Denmark)

Zhang, Jingdong; Chi, Qijin; Ulstrup, Jens

The structure, two-dimensional organization, and function of molecules immobilized on solid surfaces can be addressed in a degree of detail that has reached the level of the single-molecule. In this context redox molecules are “smart” molecules adding sophisticated electronic function. Redox meta...

Excitonic Behavior of Rhodamine Dimers: A Single-Molecule Study

NARCIS (Netherlands)

Hernando Campos, J.; van der Schaaf, Martijn; van Dijk, E.M.H.P.; Sauer, Markus; Garcia Parajo, M.F.; van Hulst, N.F.

2003-01-01

The optical behavior of a dimer of tetramethylrhodamine-5-isothiocyanate has been investigated by means of single-molecule measurements. Bulk absorption and fluorescence spectra show the existence of two populations of the dimer molecule that exhibit distinct excitonic interactions (strong and weak

Nanogap Electrodes towards Solid State Single-Molecule Transistors.

Science.gov (United States)

Cui, Ajuan; Dong, Huanli; Hu, Wenping

2015-12-01

With the establishment of complementary metal-oxide-semiconductor (CMOS)-based integrated circuit technology, it has become more difficult to follow Moore's law to further downscale the size of electronic components. Devices based on various nanostructures were constructed to continue the trend in the minimization of electronics, and molecular devices are among the most promising candidates. Compared with other candidates, molecular devices show unique superiorities, and intensive studies on molecular devices have been carried out both experimentally and theoretically at the present time. Compared to two-terminal molecular devices, three-terminal devices, namely single-molecule transistors, show unique advantages both in fundamental research and application and are considered to be an essential part of integrated circuits based on molecular devices. However, it is very difficult to construct them using the traditional microfabrication techniques directly, thus new fabrication strategies are developed. This review aims to provide an exclusive way of manufacturing solid state gated nanogap electrodes, the foundation of constructing transistors of single or a few molecules. Such single-molecule transistors have the potential to be used to build integrated circuits. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Voltage-Driven Conformational Switching with Distinct Raman Signature in a Single-Molecule Junction.

Science.gov (United States)

Bi, Hai; Palma, Carlos-Andres; Gong, Yuxiang; Hasch, Peter; Elbing, Mark; Mayor, Marcel; Reichert, Joachim; Barth, Johannes V

2018-04-11

Precisely controlling well-defined, stable single-molecule junctions represents a pillar of single-molecule electronics. Early attempts to establish computing with molecular switching arrays were partly challenged by limitations in the direct chemical characterization of metal-molecule-metal junctions. While cryogenic scanning probe studies have advanced the mechanistic understanding of current- and voltage-induced conformational switching, metal-molecule-metal conformations are still largely inferred from indirect evidence. Hence, the development of robust, chemically sensitive techniques is instrumental for advancement in the field. Here we probe the conformation of a two-state molecular switch with vibrational spectroscopy, while simultaneously operating it by means of the applied voltage. Our study emphasizes measurements of single-molecule Raman spectra in a room-temperature stable single-molecule switch presenting a signal modulation of nearly 2 orders of magnitude.

Evaluation of the Electronic Structure of Single-Molecule Junctions Based on Current-Voltage and Thermopower Measurements: Application to C60 Single-Molecule Junction.

Science.gov (United States)

Komoto, Yuki; Isshiki, Yuji; Fujii, Shintaro; Nishino, Tomoaki; Kiguchi, Manabu

2017-02-16

The electronic structure of molecular junctions has a significant impact on their transport properties. Despite the decisive role of the electronic structure, a complete characterization of the electronic structure remains a challenge. This is because there is no straightforward way of measuring electron spectroscopy for an individual molecule trapped in a nanoscale gap between two metal electrodes. Herein, a comprehensive approach to obtain a detailed description of the electronic structure in single-molecule junctions based on the analysis of current-voltage (I-V) and thermoelectric characteristics is described. It is shown that the electronic structure of the prototypical C 60 single-molecule junction can be resolved by analyzing complementary results of the I-V and thermoelectric measurement. This combined approach confirmed that the C 60 single-molecule junction was highly conductive with molecular electronic conductances of 0.033 and 0.003 G 0 and a molecular Seebeck coefficient of -12 μV K -1 . In addition, we revealed that charge transport was mediated by a LUMO whose energy level was located 0.5≈0.6 eV above the Fermi level of the Au electrode. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Single Fluorescent Molecules as Nano-Illuminators for Biological Structure and Function

Science.gov (United States)

Moerner, W. E.

2011-03-01

Since the first optical detection and spectroscopy of a single molecule in a solid (Phys. Rev. Lett. {62}, 2535 (1989)), much has been learned about the ability of single molecules to probe local nanoenvironments and individual behavior in biological and nonbiological materials in the absence of ensemble averaging that can obscure heterogeneity. Because each single fluorophore acts a light source roughly 1 nm in size, microscopic imaging of individual fluorophores leads naturally to superlocalization, or determination of the position of the molecule with precision beyond the optical diffraction limit, simply by digitization of the point-spread function from the single emitter. For example, the shape of single filaments in a living cell can be extracted simply by allowing a single molecule to move through the filament (PNAS {103}, 10929 (2006)). The addition of photoinduced control of single-molecule emission allows imaging beyond the diffraction limit (super-resolution) and a new array of acronyms (PALM, STORM, F-PALM etc.) and advances have appeared. We have used the native blinking and switching of a common yellow-emitting variant of green fluorescent protein (EYFP) reported more than a decade ago (Nature {388}, 355 (1997)) to achieve sub-40 nm super-resolution imaging of several protein structures in the bacterium Caulobacter crescentus: the quasi-helix of the actin-like protein MreB (Nat. Meth. {5}, 947 (2008)), the cellular distribution of the DNA binding protein HU (submitted), and the recently discovered division spindle composed of ParA filaments (Nat. Cell Biol. {12}, 791 (2010)). Even with these advances, better emitters would provide more photons and improved resolution, and a new photoactivatable small-molecule emitter has recently been synthesized and targeted to specific structures in living cells to provide super-resolution images (JACS {132}, 15099 (2010)). Finally, a new optical method for extracting three-dimensional position information based on

Single molecule microscopy in 3D cell cultures and tissues.

Science.gov (United States)

Lauer, Florian M; Kaemmerer, Elke; Meckel, Tobias

2014-12-15

From the onset of the first microscopic visualization of single fluorescent molecules in living cells at the beginning of this century, to the present, almost routine application of single molecule microscopy, the method has well-proven its ability to contribute unmatched detailed insight into the heterogeneous and dynamic molecular world life is composed of. Except for investigations on bacteria and yeast, almost the entire story of success is based on studies on adherent mammalian 2D cell cultures. However, despite this continuous progress, the technique was not able to keep pace with the move of the cell biology community to adapt 3D cell culture models for basic research, regenerative medicine, or drug development and screening. In this review, we will summarize the progress, which only recently allowed for the application of single molecule microscopy to 3D cell systems and give an overview of the technical advances that led to it. While initially posing a challenge, we finally conclude that relevant 3D cell models will become an integral part of the on-going success of single molecule microscopy. Copyright © 2014 Elsevier B.V. All rights reserved.

A single molecule switch based on two Pd nanocrystals linked

Indian Academy of Sciences (India)

Conducting molecule; nanocrystals; scanning tunneling microscopy; negative differential resistance. Abstract. Tunneling spectroscopy measurements have been carried out on a single molecule device formed by two Pd ... Current Issue : Vol.

Electron transfer dynamics of bistable single-molecule junctions

DEFF Research Database (Denmark)

Danilov, A.V; Kubatkin, S.; Kafanov, S. G.

2006-01-01

We present transport measurements of single-molecule junctions bridged by a molecule with three benzene rings connected by two double bonds and with thiol end-groups that allow chemical binding to gold electrodes. The I-V curves show switching behavior between two distinct states. By statistical ...... analysis of the switching events, we show that a 300 meV mode mediates the transition between the two states. We propose that breaking and reformation of a S-H bond in the contact zone between molecule and electrode explains the observed bistability....

Quantum-Sequencing: Fast electronic single DNA molecule sequencing

Science.gov (United States)

Casamada Ribot, Josep; Chatterjee, Anushree; Nagpal, Prashant

2014-03-01

A major goal of third-generation sequencing technologies is to develop a fast, reliable, enzyme-free, high-throughput and cost-effective, single-molecule sequencing method. Here, we present the first demonstration of unique ``electronic fingerprint'' of all nucleotides (A, G, T, C), with single-molecule DNA sequencing, using Quantum-tunneling Sequencing (Q-Seq) at room temperature. We show that the electronic state of the nucleobases shift depending on the pH, with most distinct states identified at acidic pH. We also demonstrate identification of single nucleotide modifications (methylation here). Using these unique electronic fingerprints (or tunneling data), we report a partial sequence of beta lactamase (bla) gene, which encodes resistance to beta-lactam antibiotics, with over 95% success rate. These results highlight the potential of Q-Seq as a robust technique for next-generation sequencing.

New Antifouling Platform Characterized by Single-Molecule Imaging

Science.gov (United States)

2015-01-01

Antifouling surfaces have been widely studied for their importance in medical devices and industry. Antifouling surfaces mostly achieved by methoxy-poly(ethylene glycol) (mPEG) have shown biomolecular adsorption less than 1 ng/cm2 which was measured by surface analytical tools such as surface plasmon resonance (SPR) spectroscopy, quartz crystal microbalance (QCM), or optical waveguide lightmode (OWL) spectroscopy. Herein, we utilize a single-molecule imaging technique (i.e., an ultimate resolution) to study antifouling properties of functionalized surfaces. We found that about 600 immunoglobulin G (IgG) molecules are adsorbed. This result corresponds to ∼5 pg/cm2 adsorption, which is far below amount for the detection limit of the conventional tools. Furthermore, we developed a new antifouling platform that exhibits improved antifouling performance that shows only 78 IgG molecules adsorbed (∼0.5 pg/cm2). The antifouling platform consists of forming 1 nm TiO2 thin layer, on which peptidomimetic antifouling polymer (PMAP) is robustly anchored. The unprecedented antifouling performance can potentially revolutionize a variety of research fields such as single-molecule imaging, medical devices, biosensors, and others. PMID:24503420

New antifouling platform characterized by single-molecule imaging.

Science.gov (United States)

Ryu, Ji Young; Song, In Taek; Lau, K H Aaron; Messersmith, Phillip B; Yoon, Tae-Young; Lee, Haeshin

2014-03-12

Antifouling surfaces have been widely studied for their importance in medical devices and industry. Antifouling surfaces mostly achieved by methoxy-poly(ethylene glycol) (mPEG) have shown biomolecular adsorption less than 1 ng/cm(2) which was measured by surface analytical tools such as surface plasmon resonance (SPR) spectroscopy, quartz crystal microbalance (QCM), or optical waveguide lightmode (OWL) spectroscopy. Herein, we utilize a single-molecule imaging technique (i.e., an ultimate resolution) to study antifouling properties of functionalized surfaces. We found that about 600 immunoglobulin G (IgG) molecules are adsorbed. This result corresponds to ∼5 pg/cm(2) adsorption, which is far below amount for the detection limit of the conventional tools. Furthermore, we developed a new antifouling platform that exhibits improved antifouling performance that shows only 78 IgG molecules adsorbed (∼0.5 pg/cm(2)). The antifouling platform consists of forming 1 nm TiO2 thin layer, on which peptidomimetic antifouling polymer (PMAP) is robustly anchored. The unprecedented antifouling performance can potentially revolutionize a variety of research fields such as single-molecule imaging, medical devices, biosensors, and others.

Single molecule experiments challenge the strict wave-particle dualism of light.

Science.gov (United States)

Greulich, Karl Otto

2010-01-21

Single molecule techniques improve our understanding of the photon and light. If the single photon double slit experiment is performed at the "single photon limit" of a multi-atom light source, faint light pulses with more than one photon hamper the interpretation. Single molecules, quantum dots or defect centres in crystals should be used as light source. "Single photon detectors" do not meet their promise-only "photon number resolving single photon detectors" do so. Particularly, the accumulation time argument, the only safe basis for the postulate of a strictly particle like photon, has so far not yet been verified.

Zero-phonon-line emission of single molecules for applications in quantum information processing

Science.gov (United States)

Kiraz, Alper; Ehrl, M.; Mustecaplioglu, O. E.; Hellerer, T.; Brauchle, C.; Zumbusch, A.

2005-07-01

A single photon source which generates transform limited single photons is highly desirable for applications in quantum optics. Transform limited emission guarantees the indistinguishability of the emitted single photons. This, in turn brings groundbreaking applications in linear optics quantum information processing within an experimental reach. Recently, self-assembled InAs quantum dots and trapped atoms have successfully been demonstrated as such sources for highly indistinguishable single photons. Here, we demonstrate that nearly transform limited zero-phonon-line (ZPL) emission from single molecules can be obtained by using vibronic excitation. Furthermore we report the results of coincidence detection experiments at the output of a Michelson-type interferometer. These experiments reveal Hong-Ou-Mandel correlations as a proof of the indistinguishability of the single photons emitted consecutively from a single molecule. Therefore, single molecules constitute an attractive alternative to single InAs quantum dots and trapped atoms for applications in linear optics quantum information processing. Experiments were performed with a home-built confocal microscope keeping the sample in a superfluid liquid Helium bath at 1.4K. We investigated terrylenediimide (TDI) molecules highly diluted in hexadecane (Shpol'skii matrix). A continuous wave single mode dye laser was used for excitation of vibronic transitions of individual molecules. From the integral fluorescence, the ZPL of single molecules was selected with a spectrally narrow interference filter. The ZPL emission was then sent to a scanning Fabry-Perot interferometer for linewidth measurements or a Michelson-type interferometer for coincidence detection.

Detection of kinetic change points in piece-wise linear single molecule motion

Science.gov (United States)

Hill, Flynn R.; van Oijen, Antoine M.; Duderstadt, Karl E.

2018-03-01

Single-molecule approaches present a powerful way to obtain detailed kinetic information at the molecular level. However, the identification of small rate changes is often hindered by the considerable noise present in such single-molecule kinetic data. We present a general method to detect such kinetic change points in trajectories of motion of processive single molecules having Gaussian noise, with a minimum number of parameters and without the need of an assumed kinetic model beyond piece-wise linearity of motion. Kinetic change points are detected using a likelihood ratio test in which the probability of no change is compared to the probability of a change occurring, given the experimental noise. A predetermined confidence interval minimizes the occurrence of false detections. Applying the method recursively to all sub-regions of a single molecule trajectory ensures that all kinetic change points are located. The algorithm presented allows rigorous and quantitative determination of kinetic change points in noisy single molecule observations without the need for filtering or binning, which reduce temporal resolution and obscure dynamics. The statistical framework for the approach and implementation details are discussed. The detection power of the algorithm is assessed using simulations with both single kinetic changes and multiple kinetic changes that typically arise in observations of single-molecule DNA-replication reactions. Implementations of the algorithm are provided in ImageJ plugin format written in Java and in the Julia language for numeric computing, with accompanying Jupyter Notebooks to allow reproduction of the analysis presented here.

Multiplex single-molecule interaction profiling of DNA-barcoded proteins.

Science.gov (United States)

Gu, Liangcai; Li, Chao; Aach, John; Hill, David E; Vidal, Marc; Church, George M

2014-11-27

In contrast with advances in massively parallel DNA sequencing, high-throughput protein analyses are often limited by ensemble measurements, individual analyte purification and hence compromised quality and cost-effectiveness. Single-molecule protein detection using optical methods is limited by the number of spectrally non-overlapping chromophores. Here we introduce a single-molecular-interaction sequencing (SMI-seq) technology for parallel protein interaction profiling leveraging single-molecule advantages. DNA barcodes are attached to proteins collectively via ribosome display or individually via enzymatic conjugation. Barcoded proteins are assayed en masse in aqueous solution and subsequently immobilized in a polyacrylamide thin film to construct a random single-molecule array, where barcoding DNAs are amplified into in situ polymerase colonies (polonies) and analysed by DNA sequencing. This method allows precise quantification of various proteins with a theoretical maximum array density of over one million polonies per square millimetre. Furthermore, protein interactions can be measured on the basis of the statistics of colocalized polonies arising from barcoding DNAs of interacting proteins. Two demanding applications, G-protein coupled receptor and antibody-binding profiling, are demonstrated. SMI-seq enables 'library versus library' screening in a one-pot assay, simultaneously interrogating molecular binding affinity and specificity.

DNA origami-based shape IDs for single-molecule nanomechanical genotyping

Science.gov (United States)

Zhang, Honglu; Chao, Jie; Pan, Dun; Liu, Huajie; Qiang, Yu; Liu, Ke; Cui, Chengjun; Chen, Jianhua; Huang, Qing; Hu, Jun; Wang, Lianhui; Huang, Wei; Shi, Yongyong; Fan, Chunhai

2017-04-01

Variations on DNA sequences profoundly affect how we develop diseases and respond to pathogens and drugs. Atomic force microscopy (AFM) provides a nanomechanical imaging approach for genetic analysis with nanometre resolution. However, unlike fluorescence imaging that has wavelength-specific fluorophores, the lack of shape-specific labels largely hampers widespread applications of AFM imaging. Here we report the development of a set of differentially shaped, highly hybridizable self-assembled DNA origami nanostructures serving as shape IDs for magnified nanomechanical imaging of single-nucleotide polymorphisms. Using these origami shape IDs, we directly genotype single molecules of human genomic DNA with an ultrahigh resolution of ~10 nm and the multiplexing ability. Further, we determine three types of disease-associated, long-range haplotypes in samples from the Han Chinese population. Single-molecule analysis allows robust haplotyping even for samples with low labelling efficiency. We expect this generic shape ID-based nanomechanical approach to hold great potential in genetic analysis at the single-molecule level.

Single-Molecule Electronics with Cross- Conjugated Molecules: Quantum Interference, IETS and Non-Equilibrium "Temperatures"

DEFF Research Database (Denmark)

Jørgensen, Jacob Lykkebo

Abstract The idea of using single-molecules as components in electronic devices is fas- cinating. For this idea to come into fruition, a number of technical and theo- retical challenges must be overcome. In this PhD thesis, the electron-phonon interaction is studied for a special class of molecules......, which is characterised by destructive quantum interference. The molecules are cross-conjugated, which means that the two parts of the molecules are conjugated to a third part, but not to each other. This gives rise to an anti-resonance in the trans- mission. In the low bias and low temperature regime......-conjugated molecules. We nd that the vibrational modes that would be expected to dominate, following the propensity, rules are very weak. Instead, other modes are found to be the dominant ones. We study this phenomenon for a number of cross-conjugated molecules, and link these ndings to the anti...

Evidence for a single hydrogen molecule connected by an atomic chain

DEFF Research Database (Denmark)

Kiguchi, M.; Stadler, Robert; Bækgaard, Iben Sig Buur

2007-01-01

Stable, single-molecule conducting-bridge configurations are typically identified from peak structures in a conductance histogram. In previous work on Pt with H-2 at cryogenic temperatures it has been shown that a peak near 1G(0) identifies a single-molecule Pt-H-2-Pt bridge. The histogram shows...

Surface Passivation for Single-molecule Protein Studies

Science.gov (United States)

Chandradoss, Stanley D.; Haagsma, Anna C.; Lee, Young Kwang; Hwang, Jae-Ho; Nam, Jwa-Min; Joo, Chirlmin

2014-01-01

Single-molecule fluorescence spectroscopy has proven to be instrumental in understanding a wide range of biological phenomena at the nanoscale. Important examples of what this technique can yield to biological sciences are the mechanistic insights on protein-protein and protein-nucleic acid interactions. When interactions of proteins are probed at the single-molecule level, the proteins or their substrates are often immobilized on a glass surface, which allows for a long-term observation. This immobilization scheme may introduce unwanted surface artifacts. Therefore, it is essential to passivate the glass surface to make it inert. Surface coating using polyethylene glycol (PEG) stands out for its high performance in preventing proteins from non-specifically interacting with a glass surface. However, the polymer coating procedure is difficult, due to the complication arising from a series of surface treatments and the stringent requirement that a surface needs to be free of any fluorescent molecules at the end of the procedure. Here, we provide a robust protocol with step-by-step instructions. It covers surface cleaning including piranha etching, surface functionalization with amine groups, and finally PEG coating. To obtain a high density of a PEG layer, we introduce a new strategy of treating the surface with PEG molecules over two rounds, which remarkably improves the quality of passivation. We provide representative results as well as practical advice for each critical step so that anyone can achieve the high quality surface passivation. PMID:24797261

Information and Entropy

Science.gov (United States)

Caticha, Ariel

2007-11-01

What is information? Is it physical? We argue that in a Bayesian theory the notion of information must be defined in terms of its effects on the beliefs of rational agents. Information is whatever constrains rational beliefs and therefore it is the force that induces us to change our minds. This problem of updating from a prior to a posterior probability distribution is tackled through an eliminative induction process that singles out the logarithmic relative entropy as the unique tool for inference. The resulting method of Maximum relative Entropy (ME), which is designed for updating from arbitrary priors given information in the form of arbitrary constraints, includes as special cases both MaxEnt (which allows arbitrary constraints) and Bayes' rule (which allows arbitrary priors). Thus, ME unifies the two themes of these workshops—the Maximum Entropy and the Bayesian methods—into a single general inference scheme that allows us to handle problems that lie beyond the reach of either of the two methods separately. I conclude with a couple of simple illustrative examples.

A Single-Molecule Barcoding System using Nanoslits for DNA Analysis

Science.gov (United States)

Jo, Kyubong; Schramm, Timothy M.; Schwartz, David C.

Single DNA molecule approaches are playing an increasingly central role in the analytical genomic sciences because single molecule techniques intrinsically provide individualized measurements of selected molecules, free from the constraints of bulk techniques, which blindly average noise and mask the presence of minor analyte components. Accordingly, a principal challenge that must be addressed by all single molecule approaches aimed at genome analysis is how to immobilize and manipulate DNA molecules for measurements that foster construction of large, biologically relevant data sets. For meeting this challenge, this chapter discusses an integrated approach for microfabricated and nanofabricated devices for the manipulation of elongated DNA molecules within nanoscale geometries. Ideally, large DNA coils stretch via nanoconfinement when channel dimensions are within tens of nanometers. Importantly, stretched, often immobilized, DNA molecules spanning hundreds of kilobase pairs are required by all analytical platforms working with large genomic substrates because imaging techniques acquire sequence information from molecules that normally exist in free solution as unrevealing random coils resembling floppy balls of yarn. However, nanoscale devices fabricated with sufficiently small dimensions fostering molecular stretching make these devices impractical because of the requirement of exotic fabrication technologies, costly materials, and poor operational efficiencies. In this chapter, such problems are addressed by discussion of a new approach to DNA presentation and analysis that establishes scaleable nanoconfinement conditions through reduction of ionic strength; stiffening DNA molecules thus enabling their arraying for analysis using easily fabricated devices that can also be mass produced. This new approach to DNA nanoconfinement is complemented by the development of a novel labeling scheme for reliable marking of individual molecules with fluorochrome labels

Single Molecule Experiments Challenge the Strict Wave-Particle Dualism of Light

Directory of Open Access Journals (Sweden)

Karl Otto Greulich

2010-01-01

Full Text Available Single molecule techniques improve our understanding of the photon and light. If the single photon double slit experiment is performed at the “single photon limit” of a multi-atom light source, faint light pulses with more than one photon hamper the interpretation. Single molecules, quantum dots or defect centres in crystals should be used as light source. “Single photon detectors” do not meet their promise―only “photon number resolving single photon detectors” do so. Particularly, the accumulation time argument, the only safe basis for the postulate of a strictly particle like photon, has so far not yet been verified.

Site-Selection in Single-Molecule Junction for Highly Reproducible Molecular Electronics.

Science.gov (United States)

Kaneko, Satoshi; Murai, Daigo; Marqués-González, Santiago; Nakamura, Hisao; Komoto, Yuki; Fujii, Shintaro; Nishino, Tomoaki; Ikeda, Katsuyoshi; Tsukagoshi, Kazuhito; Kiguchi, Manabu

2016-02-03

Adsorption sites of molecules critically determine the electric/photonic properties and the stability of heterogeneous molecule-metal interfaces. Then, selectivity of adsorption site is essential for development of the fields including organic electronics, catalysis, and biology. However, due to current technical limitations, site-selectivity, i.e., precise determination of the molecular adsorption site, remains a major challenge because of difficulty in precise selection of meaningful one among the sites. We have succeeded the single site-selection at a single-molecule junction by performing newly developed hybrid technique: simultaneous characterization of surface enhanced Raman scattering (SERS) and current-voltage (I-V) measurements. The I-V response of 1,4-benzenedithiol junctions reveals the existence of three metastable states arising from different adsorption sites. Notably, correlated SERS measurements show selectivity toward one of the adsorption sites: "bridge sites". This site-selectivity represents an essential step toward the reliable integration of individual molecules on metallic surfaces. Furthermore, the hybrid spectro-electric technique reveals the dependence of the SERS intensity on the strength of the molecule-metal interaction, showing the interdependence between the optical and electronic properties in single-molecule junctions.

Single molecule DNA detection with an atomic vapor notch filter

Energy Technology Data Exchange (ETDEWEB)

Uhland, Denis; Rendler, Torsten; Widmann, Matthias; Lee, Sang-Yun [University of Stuttgart and Stuttgart Research Center of Photonic Engineering (SCoPE) and IQST, 3rd Physics Institute, Stuttgart (Germany); Wrachtrup, Joerg; Gerhardt, Ilja [University of Stuttgart and Stuttgart Research Center of Photonic Engineering (SCoPE) and IQST, 3rd Physics Institute, Stuttgart (Germany); Max Planck Institute for Solid State Research, Stuttgart (Germany)

2015-12-01

The detection of single molecules has facilitated many advances in life- and material-science. Commonly the fluorescence of dye molecules is detected, which are attached to a non-fluorescent structure under study. For fluorescence microscopy one desires to maximize the detection efficiency together with an efficient suppression of undesired laser leakage. Here we present the use of the narrow-band filtering properties of hot atomic sodium vapor to selectively filter the excitation light from the red-shifted fluorescence of dye labeled single-stranded DNA molecules. A statistical analysis proves an enhancement in detection efficiency of more than 15% in a confocal and in a wide-field configuration. (orig.)

Parameters Tuning of Model Free Adaptive Control Based on Minimum Entropy

Institute of Scientific and Technical Information of China (English)

Chao Ji; Jing Wang; Liulin Cao; Qibing Jin

2014-01-01

Dynamic linearization based model free adaptive control(MFAC) algorithm has been widely used in practical systems, in which some parameters should be tuned before it is successfully applied to process industries. Considering the random noise existing in real processes, a parameter tuning method based on minimum entropy optimization is proposed,and the feature of entropy is used to accurately describe the system uncertainty. For cases of Gaussian stochastic noise and non-Gaussian stochastic noise, an entropy recursive optimization algorithm is derived based on approximate model or identified model. The extensive simulation results show the effectiveness of the minimum entropy optimization for the partial form dynamic linearization based MFAC. The parameters tuned by the minimum entropy optimization index shows stronger stability and more robustness than these tuned by other traditional index,such as integral of the squared error(ISE) or integral of timeweighted absolute error(ITAE), when the system stochastic noise exists.

Single-Molecule Sensing with Nanopore Confinement: from Chemical Reactions to Biological Interactions.

Science.gov (United States)

Lin, Yao; Ying, Yi-Lun; Gao, Rui; Long, Yi-Tao

2018-03-25

The nanopore can generate an electrochemical confinement for single-molecule sensing which help understand the fundamental chemical principle in nanoscale dimensions. By observing the generated ionic current, individual bond-making and bond-breaking steps, single biomolecule dynamic conformational changes and electron transfer processes that occur within pore can be monitored with high temporal and current resolution. These single-molecule studies in nanopore confinement are revealing information about the fundamental chemical and biological processes that cannot be extracted from ensemble measurements. In this concept, we introduce and discuss the electrochemical confinement effects on single-molecule covalent reactions, conformational dynamics of individual molecules and host-guest interactions in protein nanopores. Then, we extend the concept of nanopore confinement effects to confine electrochemical redox reactions in solid-state nanopores for developing new sensing mechanisms. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Single-molecule diffusion and conformational dynamics by spatial integration of temporal fluctuations

KAUST Repository

Serag, Maged F.

2014-10-06

Single-molecule localization and tracking has been used to translate spatiotemporal information of individual molecules to map their diffusion behaviours. However, accurate analysis of diffusion behaviours and including other parameters, such as the conformation and size of molecules, remain as limitations to the method. Here, we report a method that addresses the limitations of existing single-molecular localization methods. The method is based on temporal tracking of the cumulative area occupied by molecules. These temporal fluctuations are tied to molecular size, rates of diffusion and conformational changes. By analysing fluorescent nanospheres and double-stranded DNA molecules of different lengths and topological forms, we demonstrate that our cumulative-area method surpasses the conventional single-molecule localization method in terms of the accuracy of determined diffusion coefficients. Furthermore, the cumulative-area method provides conformational relaxation times of structurally flexible chains along with diffusion coefficients, which together are relevant to work in a wide spectrum of scientific fields.

Single-molecule diffusion and conformational dynamics by spatial integration of temporal fluctuations

KAUST Repository

Serag, Maged F.; Abadi, Maram; Habuchi, Satoshi

2014-01-01

Single-molecule localization and tracking has been used to translate spatiotemporal information of individual molecules to map their diffusion behaviours. However, accurate analysis of diffusion behaviours and including other parameters, such as the conformation and size of molecules, remain as limitations to the method. Here, we report a method that addresses the limitations of existing single-molecular localization methods. The method is based on temporal tracking of the cumulative area occupied by molecules. These temporal fluctuations are tied to molecular size, rates of diffusion and conformational changes. By analysing fluorescent nanospheres and double-stranded DNA molecules of different lengths and topological forms, we demonstrate that our cumulative-area method surpasses the conventional single-molecule localization method in terms of the accuracy of determined diffusion coefficients. Furthermore, the cumulative-area method provides conformational relaxation times of structurally flexible chains along with diffusion coefficients, which together are relevant to work in a wide spectrum of scientific fields.

Large rotating field entropy change in ErFeO3 single crystal with angular distribution contribution

Science.gov (United States)

Huang, Ruoxiang; Cao, Shixun; Ren, Wei; Zhan, Sheng; Kang, Baojuan; Zhang, Jincang

2013-10-01

We report the rotating field entropy of ErFeO3 single-crystal in a temperature range of 3-40 K. The giant magnetic entropy change, ΔSM = -20.7 J/(kg K), and the refrigerant capacity, RC = 273.5 J/kg, are observed near T =6 K. The anisotropic constants at 6 K, K1 = 1.24× 103 J/kg, K2 = 0.74 × 103 J/kg, in the bc plane are obtained. By considering the magnetocrystalline anisotropy and Fermi-Dirac angular distribution along the orientation of spontaneous magnetization, the experimental results can be well simulated. Our present work demonstrates that ErFeO3 crystal may find practical use for low temperature anisotropic magnetic refrigeration.

Machine learning approach for single molecule localisation microscopy.

Science.gov (United States)

Colabrese, Silvia; Castello, Marco; Vicidomini, Giuseppe; Del Bue, Alessio

2018-04-01

Single molecule localisation (SML) microscopy is a fundamental tool for biological discoveries; it provides sub-diffraction spatial resolution images by detecting and localizing "all" the fluorescent molecules labeling the structure of interest. For this reason, the effective resolution of SML microscopy strictly depends on the algorithm used to detect and localize the single molecules from the series of microscopy frames. To adapt to the different imaging conditions that can occur in a SML experiment, all current localisation algorithms request, from the microscopy users, the choice of different parameters. This choice is not always easy and their wrong selection can lead to poor performance. Here we overcome this weakness with the use of machine learning. We propose a parameter-free pipeline for SML learning based on support vector machine (SVM). This strategy requires a short supervised training that consists in selecting by the user few fluorescent molecules (∼ 10-20) from the frames under analysis. The algorithm has been extensively tested on both synthetic and real acquisitions. Results are qualitatively and quantitatively consistent with the state of the art in SML microscopy and demonstrate that the introduction of machine learning can lead to a new class of algorithms competitive and conceived from the user point of view.

Light-Induced Switching of Tunable Single-Molecule Junctions

KAUST Repository

Sendler, Torsten; Luka-Guth, Katharina; Wieser, Matthias; Lokamani; Wolf, Jannic Sebastian; Helm, Manfred; Gemming, Sibylle; Kerbusch, Jochen; Scheer, Elke; Huhn, Thomas; Erbe, Artur

2015-01-01

A major goal of molecular electronics is the development and implementation of devices such as single-molecular switches. Here, measurements are presented that show the controlled in situ switching of diarylethene molecules from their nonconductive to conductive state in contact to gold nanoelectrodes via controlled light irradiation. Both the conductance and the quantum yield for switching of these molecules are within a range making the molecules suitable for actual devices. The conductance of the molecular junctions in the opened and closed states is characterized and the molecular level E 0, which dominates the current transport in the closed state, and its level broadening Γ are identified. The obtained results show a clear light-induced ring forming isomerization of the single-molecule junctions. Electron withdrawing side-groups lead to a reduction of conductance, but do not influence the efficiency of the switching mechanism. Quantum chemical calculations of the light-induced switching processes correlate these observations with the fundamentally different low-lying electronic states of the opened and closed forms and their comparably small modification by electron-withdrawing substituents. This full characterization of a molecular switch operated in a molecular junction is an important step toward the development of real molecular electronics devices.

Light-Induced Switching of Tunable Single-Molecule Junctions

KAUST Repository

Sendler, Torsten

2015-04-16

A major goal of molecular electronics is the development and implementation of devices such as single-molecular switches. Here, measurements are presented that show the controlled in situ switching of diarylethene molecules from their nonconductive to conductive state in contact to gold nanoelectrodes via controlled light irradiation. Both the conductance and the quantum yield for switching of these molecules are within a range making the molecules suitable for actual devices. The conductance of the molecular junctions in the opened and closed states is characterized and the molecular level E 0, which dominates the current transport in the closed state, and its level broadening Γ are identified. The obtained results show a clear light-induced ring forming isomerization of the single-molecule junctions. Electron withdrawing side-groups lead to a reduction of conductance, but do not influence the efficiency of the switching mechanism. Quantum chemical calculations of the light-induced switching processes correlate these observations with the fundamentally different low-lying electronic states of the opened and closed forms and their comparably small modification by electron-withdrawing substituents. This full characterization of a molecular switch operated in a molecular junction is an important step toward the development of real molecular electronics devices.

Linker-dependent Junction Formation Probability in Single-Molecule Junctions

Energy Technology Data Exchange (ETDEWEB)

Yoo, Pil Sun; Kim, Taekyeong [HankukUniversity of Foreign Studies, Yongin (Korea, Republic of)

2015-01-15

We compare the junction formation probabilities of single-molecule junctions with different linker molecules by using a scanning tunneling microscope-based break-junction technique. We found that the junction formation probability varies as SH > SMe > NH2 for the benzene backbone molecule with different types of anchoring groups, through quantitative statistical analysis. These results are attributed to different bonding forces according to the linker groups formed with Au atoms in the electrodes, which is consistent with previous works. Our work allows a better understanding of the contact chemistry in the metal.molecule junction for future molecular electronic devices.

Structural and electronic properties of single molecules and organic layers on surfaces

NARCIS (Netherlands)

Sotthewes, Kai

2016-01-01

Single molecules and organic layers on well-defined solid surfaces have attracted tremendous attention owing to their interesting physical and chemical properties. The ultimate utility of single molecules or self-assembled monolayers (SAMs) for potential applications is critically dependent on the

Electrochemistry and bioelectrochemistry towards the single-molecule level: Theoretical notions and systems

DEFF Research Database (Denmark)

Zhang, Jingdong; Chi, Qijin; Albrecht, Tim

2005-01-01

Surface structures controlled at the nanometer and single-molecule levels, with functions crucially determined by interfacial electron transfer (ET) are broadly reported in recent years, with different kinds of electrochemically controlled nanoscale/single molecule systems. One is the broad class...

Excitonic Coupling in Linear and Trefoil Trimer Perylenediimide Molecules Probed by Single-Molecule Spectroscopy

KAUST Repository

Yoo, Hyejin

2012-10-25

Perylenediimide (PDI) molecules are promising building blocks for photophysical studies of electronic interactions within multichromophore arrays. Such PDI arrays are important materials for fabrication of molecular nanodevices such as organic light-emitting diodes, organic semiconductors, and biosensors because of their high photostability, chemical and physical inertness, electron affinity, and high tinctorial strength over the entire visible spectrum. In this work, PDIs have been organized into linear (L3) and trefoil (T3) trimer molecules and investigated by single-molecule fluorescence microscopy to probe the relationship between molecular structures and interchromophoric electronic interactions. We found a broad distribution of coupling strengths in both L3 and T3 and hence strong/weak coupling between PDI units by monitoring spectral peak shifts in single-molecule fluorescence spectra upon sequential photobleaching of each constituent chromophore. In addition, we used a wide-field defocused imaging technique to resolve heterogeneities in molecular structures of L3 and T3 embedded in a PMMA polymer matrix. A systematic comparison between the two sets of experimental results allowed us to infer the correlation between intermolecular interactions and molecular structures. Our results show control of the PDI intermolecular interactions using suitable multichromophoric structures. © 2012 American Chemical Society.

Excitonic Coupling in Linear and Trefoil Trimer Perylenediimide Molecules Probed by Single-Molecule Spectroscopy

KAUST Repository

Yoo, Hyejin; Furumaki, Shu; Yang, Jaesung; Lee, Ji-Eun; Chung, Heejae; Oba, Tatsuya; Kobayashi, Hiroyuki; Rybtchinski, Boris; Wilson, Thea M.; Wasielewski, Michael R.; Vacha, Martin; Kim, Dongho

2012-01-01

Perylenediimide (PDI) molecules are promising building blocks for photophysical studies of electronic interactions within multichromophore arrays. Such PDI arrays are important materials for fabrication of molecular nanodevices such as organic light-emitting diodes, organic semiconductors, and biosensors because of their high photostability, chemical and physical inertness, electron affinity, and high tinctorial strength over the entire visible spectrum. In this work, PDIs have been organized into linear (L3) and trefoil (T3) trimer molecules and investigated by single-molecule fluorescence microscopy to probe the relationship between molecular structures and interchromophoric electronic interactions. We found a broad distribution of coupling strengths in both L3 and T3 and hence strong/weak coupling between PDI units by monitoring spectral peak shifts in single-molecule fluorescence spectra upon sequential photobleaching of each constituent chromophore. In addition, we used a wide-field defocused imaging technique to resolve heterogeneities in molecular structures of L3 and T3 embedded in a PMMA polymer matrix. A systematic comparison between the two sets of experimental results allowed us to infer the correlation between intermolecular interactions and molecular structures. Our results show control of the PDI intermolecular interactions using suitable multichromophoric structures. © 2012 American Chemical Society.

Chemical Principles and Interference in the Electrical Conductance of Single Molecules

DEFF Research Database (Denmark)

Borges, Anders Christian

, the conductance of molecules can vary orders of magnitude and the concept of interference is believed to play a major role in this. This thesis investigates the links between single molecule conductance, chemistry and interference effects in short organic molecules. It is investigated to which extent...... the conductance can be understood in terms of separate contributions and when the effects of interference are important. Links between chemical principles and constructive- and destructive interference effects are demonstrated using a combination of simple models, atomistic calculations and Scanning......-Tunneling Microscope Break-Junction experiments (STM-BJ). It is demonstrated that these links can be used to design molecules exhibiting surprising interference effects and to interpret and predict the trends in the characteristic conductance of single molecules without resorting to numerical computational methods...

Spectrally resolved single-molecule electrometry

Science.gov (United States)

Ruggeri, F.; Krishnan, M.

2018-03-01

Escape-time electrometry is a recently developed experimental technique that offers the ability to measure the effective electrical charge of a single biomolecule in solution with sub-elementary charge precision. The approach relies on measuring the average escape-time of a single charged macromolecule or molecular species transiently confined in an electrostatic fluidic trap. Comparing the experiments with the predictions of a mean-field model of molecular electrostatics, we have found that the measured effective charge even reports on molecular conformation, e.g., folded or disordered state, and non-uniform charge distribution in disordered proteins or polyelectrolytes. Here we demonstrate the ability to use the spectral dimension to distinguish minute differences in electrical charge between individual molecules or molecular species in a single simultaneous measurement, under identical experimental conditions. Using one spectral channel for referenced measurement, this kind of photophysical distinguishability essentially eliminates the need for accurate knowledge of key experimental parameters, otherwise obtained through intensive characterization of the experimental setup. As examples, we demonstrate the ability to detect small differences (˜5%) in the length of double-stranded DNA fragments as well as single amino acid exchange in an intrinsically disordered protein, prothymosin α.

2012 Gordon Research Conference, Single molecule approaches to biology, July 15-20 2012

Energy Technology Data Exchange (ETDEWEB)

Fernandez, Julio M. [Columbia Univ., New York, NY (United States)

2012-04-20

Single molecule techniques are rapidly occupying a central role in biological research at all levels. This transition was made possible by the availability and dissemination of robust techniques that use fluorescence and force probes to track the conformation of molecules one at a time, in vitro as well as in live cells. Single-molecule approaches have changed the way many biological problems are studied. These novel techniques provide previously unobtainable data on fundamental biochemical processes that are essential for all forms of life. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of the molecular systems that underpin the functioning of living cells. Hence, our conference seeks to disseminate the implementation and use of single molecule techniques in the pursuit of new biological knowledge. Topics covered include: Molecular Motors on the Move; Origin And Fate Of Proteins; Physical Principles Of Life; Molecules and Super-resolution Microscopy; Nanoswitches In Action; Active Motion Or Random Diffusion?; Building Blocks Of Living Cells; From Molecular Mechanics To Physiology; Tug-of-war: Force Spectroscopy Of Single Proteins.

Blinking effect and the use of quantum dots in single molecule spectroscopy

International Nuclear Information System (INIS)

Rombach-Riegraf, Verena; Oswald, Peter; Bienert, Roland; Petersen, Jan; Domingo, M.P.; Pardo, Julian; Gräber, P.; Galvez, E.M.

2013-01-01

Highlights: ► It is possible to eliminate the blinking effect of a water-soluble QD. ► We provide a direct method to study protein function and dynamics at the single level. ► QD, potent tool for single molecule studies of biochemical and biological processes. -- Abstract: Luminescent semiconductor nanocrystals (quantum dots, QD) have unique photo-physical properties: high photostability, brightness and narrow size-tunable fluorescence spectra. Due to their unique properties, QD-based single molecule studies have become increasingly more popular during the last years. However QDs show a strong blinking effect (random and intermittent light emission), which may limit their use in single molecule fluorescence studies. QD blinking has been widely studied and some hypotheses have been done to explain this effect. Here we summarise what is known about the blinking effect in QDs, how this phenomenon may affect single molecule studies and, on the other hand, how the “on”/“off” states can be exploited in diverse experimental settings. In addition, we present results showing that site-directed binding of QD to cysteine residues of proteins reduces the blinking effect. This option opens a new possibility of using QDs to study protein–protein interactions and dynamics by single molecule fluorescence without modifying the chemical composition of the solution or the QD surface.

Blinking effect and the use of quantum dots in single molecule spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Rombach-Riegraf, Verena; Oswald, Peter; Bienert, Roland; Petersen, Jan [Albert-Ludwigs-Universitaet Freiburg, Institut fuer Physikalische Chemie, Albertstrasse 23a, 79104 Freiburg (Germany); Domingo, M.P. [Instituto de Carboquimica (CSIC), Miguel Luesma 4, 50018 Zaragoza (Spain); Pardo, Julian [Grupo Apoptosis, Inmunidad y Cancer, Departamento Bioquimica y Biologia Molecular y Celular, Fac. Ciencias, Universidad de Zaragoza, Zaragoza (Spain); Fundacion Aragon I-D (ARAID), Gobierno de Aragon, Zaragoza (Spain); Immune Effector Cells Group, Aragon Health Research Institute (IIS Aragon), Biomedical Research Centre of Aragon (CIBA) Fundacion Aragon I-D - ARAID, Gobierno de Aragon, Zaragoza (Spain); Graeber, P. [Albert-Ludwigs-Universitaet Freiburg, Institut fuer Physikalische Chemie, Albertstrasse 23a, 79104 Freiburg (Germany); Galvez, E.M., E-mail: eva@icb.csic.es [Instituto de Carboquimica (CSIC), Miguel Luesma 4, 50018 Zaragoza (Spain); Immune Effector Cells Group, Aragon Health Research Institute (IIS Aragon), Biomedical Research Centre of Aragon (CIBA) Fundacion Aragon I-D - ARAID, Gobierno de Aragon, Zaragoza (Spain)

2013-01-04

Highlights: Black-Right-Pointing-Pointer It is possible to eliminate the blinking effect of a water-soluble QD. Black-Right-Pointing-Pointer We provide a direct method to study protein function and dynamics at the single level. Black-Right-Pointing-Pointer QD, potent tool for single molecule studies of biochemical and biological processes. -- Abstract: Luminescent semiconductor nanocrystals (quantum dots, QD) have unique photo-physical properties: high photostability, brightness and narrow size-tunable fluorescence spectra. Due to their unique properties, QD-based single molecule studies have become increasingly more popular during the last years. However QDs show a strong blinking effect (random and intermittent light emission), which may limit their use in single molecule fluorescence studies. QD blinking has been widely studied and some hypotheses have been done to explain this effect. Here we summarise what is known about the blinking effect in QDs, how this phenomenon may affect single molecule studies and, on the other hand, how the 'on'/'off' states can be exploited in diverse experimental settings. In addition, we present results showing that site-directed binding of QD to cysteine residues of proteins reduces the blinking effect. This option opens a new possibility of using QDs to study protein-protein interactions and dynamics by single molecule fluorescence without modifying the chemical composition of the solution or the QD surface.

Glass Transition, Crystallization of Glass-Forming Melts, and Entropy

Directory of Open Access Journals (Sweden)

Jürn W. P. Schmelzer

2018-02-01

Full Text Available A critical analysis of possible (including some newly proposed definitions of the vitreous state and the glass transition is performed and an overview of kinetic criteria of vitrification is presented. On the basis of these results, recent controversial discussions on the possible values of the residual entropy of glasses are reviewed. Our conclusion is that the treatment of vitrification as a process of continuously breaking ergodicity with entropy loss and a residual entropy tending to zero in the limit of zero absolute temperature is in disagreement with the absolute majority of experimental and theoretical investigations of this process and the nature of the vitreous state. This conclusion is illustrated by model computations. In addition to the main conclusion derived from these computations, they are employed as a test for several suggestions concerning the behavior of thermodynamic coefficients in the glass transition range. Further, a brief review is given on possible ways of resolving the Kauzmann paradox and its implications with respect to the validity of the third law of thermodynamics. It is shown that neither in its primary formulations nor in its consequences does the Kauzmann paradox result in contradictions with any basic laws of nature. Such contradictions are excluded by either crystallization (not associated with a pseudospinodal as suggested by Kauzmann or a conventional (and not an ideal glass transition. Some further so far widely unexplored directions of research on the interplay between crystallization and glass transition are anticipated, in which entropy may play—beyond the topics widely discussed and reviewed here—a major role.

Plasmonic tunnel junctions for single-molecule redox chemistry.

Science.gov (United States)

de Nijs, Bart; Benz, Felix; Barrow, Steven J; Sigle, Daniel O; Chikkaraddy, Rohit; Palma, Aniello; Carnegie, Cloudy; Kamp, Marlous; Sundararaman, Ravishankar; Narang, Prineha; Scherman, Oren A; Baumberg, Jeremy J

2017-10-20

Nanoparticles attached just above a flat metallic surface can trap optical fields in the nanoscale gap. This enables local spectroscopy of a few molecules within each coupled plasmonic hotspot, with near thousand-fold enhancement of the incident fields. As a result of non-radiative relaxation pathways, the plasmons in such sub-nanometre cavities generate hot charge carriers, which can catalyse chemical reactions or induce redox processes in molecules located within the plasmonic hotspots. Here, surface-enhanced Raman spectroscopy allows us to track these hot-electron-induced chemical reduction processes in a series of different aromatic molecules. We demonstrate that by increasing the tunnelling barrier height and the dephasing strength, a transition from coherent to hopping electron transport occurs, enabling observation of redox processes in real time at the single-molecule level.

Viruses and Tetraspanins: Lessons from Single Molecule Approaches

Science.gov (United States)

Dahmane, Selma; Rubinstein, Eric; Milhiet, Pierre-Emmanuel

2014-01-01

Tetraspanins are four-span membrane proteins that are widely distributed in multi-cellular organisms and involved in several infectious diseases. They have the unique property to form a network of protein-protein interaction within the plasma membrane, due to the lateral associations with one another and with other membrane proteins. Tracking tetraspanins at the single molecule level using fluorescence microscopy has revealed the membrane behavior of the tetraspanins CD9 and CD81 in epithelial cell lines, providing a first dynamic view of this network. Single molecule tracking highlighted that these 2 proteins can freely diffuse within the plasma membrane but can also be trapped, permanently or transiently, in tetraspanin-enriched areas. More recently, a similar strategy has been used to investigate tetraspanin membrane behavior in the context of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection. In this review we summarize the main results emphasizing the relationship in terms of membrane partitioning between tetraspanins, some of their partners such as Claudin-1 and EWI-2, and viral proteins during infection. These results will be analyzed in the context of other membrane microdomains, stressing the difference between raft and tetraspanin-enriched microdomains, but also in comparison with virus diffusion at the cell surface. New advanced single molecule techniques that could help to further explore tetraspanin assemblies will be also discussed. PMID:24800676

Transport mirages in single-molecule devices

Science.gov (United States)

Gaudenzi, R.; Misiorny, M.; Burzurí, E.; Wegewijs, M. R.; van der Zant, H. S. J.

2017-03-01

Molecular systems can exhibit a complex, chemically tailorable inner structure which allows for targeting of specific mechanical, electronic, and optical properties. At the single-molecule level, two major complementary ways to explore these properties are molecular quantum-dot structures and scanning probes. This article outlines comprehensive principles of electron-transport spectroscopy relevant to both these approaches and presents a new, high-resolution experiment on a high-spin single-molecule junction exemplifying these principles. Such spectroscopy plays a key role in further advancing our understanding of molecular and atomic systems, in particular, the relaxation of their spin. In this joint experimental and theoretical analysis, particular focus is put on the crossover between the resonant regime [single-electron tunneling] and the off-resonant regime [inelastic electron (co)tunneling spectroscopy (IETS)]. We show that the interplay of these two processes leads to unexpected mirages of resonances not captured by either of the two pictures alone. Although this turns out to be important in a large fraction of the possible regimes of level positions and bias voltages, it has been given little attention in molecular transport studies. Combined with nonequilibrium IETS—four-electron pump-probe excitations—these mirages provide crucial information on the relaxation of spin excitations. Our encompassing physical picture is supported by a master-equation approach that goes beyond weak coupling. The present work encourages the development of a broader connection between the fields of molecular quantum-dot and scanning probe spectroscopy.

Plasmonics and single-molecule detection in evaporated silver-island films

Energy Technology Data Exchange (ETDEWEB)

Moula, G.; Aroca, R.F. [Materials and Surface Science Group, University of Windsor, Ontario (Canada); Rodriguez-Oliveros, R.; Sanchez-Gil, J.A. [Instituto de Estructura de la Materia, Consejo Superior de Investigaciones Cientificas, Serrano 121, 28006 Madrid (Spain); Albella, P. [Centro de Fisica de Materiales (CSIC-UPV/EHU) and Donostia International Physics Center (DIPC), 20018 Donostia, San Sebastian (Spain)

2012-11-15

The plasmonic origin of surface-enhanced Raman scattering (SERS) leads to the concept of hotspots and plasmon coupling that can be realized in the interstitial regions, or on specially engineered, silver and gold nanostructures. It is also possible to achieve spatial locations of high local field or hotspots on silver-island films (SIF) allowing single-molecule detection (SMD). When a single monomolecular layer coating the SIFs contains dye molecules dispersed in it, single-molecule impurities, (with an average of one hundred dye molecules in 1 {mu}m{sup 2}, which is the field of view of the micro-Raman system), SMD is observed as a rare statistical event. Here, the SMD results for silver-island films are presented, with the same nominal mass thickness, but differing in the localized surface plasmon resonance that is a function of the temperature of substrate during deposition. A blue-shifted plasmon can be seen as a decrease in plasmon coupling for deposition at higher temperature. A simple two-particle model for localized plasmon resonance coupling calculations, including the shape and substrate effects seems to explain the trend of observations. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Maximum entropy methods

International Nuclear Information System (INIS)

Ponman, T.J.

1984-01-01

For some years now two different expressions have been in use for maximum entropy image restoration and there has been some controversy over which one is appropriate for a given problem. Here two further entropies are presented and it is argued that there is no single correct algorithm. The properties of the four different methods are compared using simple 1D simulations with a view to showing how they can be used together to gain as much information as possible about the original object. (orig.)

Experimental demonstration of a single-molecule electric motor.

Science.gov (United States)

Tierney, Heather L; Murphy, Colin J; Jewell, April D; Baber, Ashleigh E; Iski, Erin V; Khodaverdian, Harout Y; McGuire, Allister F; Klebanov, Nikolai; Sykes, E Charles H

2011-09-04

For molecules to be used as components in molecular machines, methods that couple individual molecules to external energy sources and that selectively excite motion in a given direction are required. Significant progress has been made in the construction of molecular motors powered by light and by chemical reactions, but electrically driven motors have not yet been built, despite several theoretical proposals for such motors. Here we report that a butyl methyl sulphide molecule adsorbed on a copper surface can be operated as a single-molecule electric motor. Electrons from a scanning tunnelling microscope are used to drive the directional motion of the molecule in a two-terminal setup. Moreover, the temperature and electron flux can be adjusted to allow each rotational event to be monitored at the molecular scale in real time. The direction and rate of the rotation are related to the chiralities of both the molecule and the tip of the microscope (which serves as the electrode), illustrating the importance of the symmetry of the metal contacts in atomic-scale electrical devices.

Single Molecule Raman Detection of Enkephalin on Silver Colloidal Particles

DEFF Research Database (Denmark)

Kneipp, Katrin; Kneipp, Holger; Abdali, Salim

2004-01-01

the Raman signal the enkephalin molecules have been attached to silver colloidal cluster structures. The experiments demonstrate that the SERS signal of the strongly enhanced ring breathing vibration of phenylalanine at 1000 cm-1 can be used as “intrinsic marker” for detecting a single enkephalin molecule...... and for monitoring its diffusion on the surface of the silver colloidal cluster without using a specific label molecule....

Click strategies for single-molecule protein fluorescence.

Science.gov (United States)

Milles, Sigrid; Tyagi, Swati; Banterle, Niccolò; Koehler, Christine; VanDelinder, Virginia; Plass, Tilman; Neal, Adrian P; Lemke, Edward A

2012-03-21

Single-molecule methods have matured into central tools for studies in biology. Foerster resonance energy transfer (FRET) techniques, in particular, have been widely applied to study biomolecular structure and dynamics. The major bottleneck for a facile and general application of these studies arises from the need to label biological samples site-specifically with suitable fluorescent dyes. In this work, we present an optimized strategy combining click chemistry and the genetic encoding of unnatural amino acids (UAAs) to overcome this limitation for proteins. We performed a systematic study with a variety of clickable UAAs and explored their potential for high-resolution single-molecule FRET (smFRET). We determined all parameters that are essential for successful single-molecule studies, such as accessibility of the probes, expression yield of proteins, and quantitative labeling. Our multiparameter fluorescence analysis allowed us to gain new insights into the effects and photophysical properties of fluorescent dyes linked to various UAAs for smFRET measurements. This led us to determine that, from the extended tool set that we now present, genetically encoding propargyllysine has major advantages for state-of-the-art measurements compared to other UAAs. Using this optimized system, we present a biocompatible one-step dual-labeling strategy of the regulatory protein RanBP3 with full labeling position freedom. Our technique allowed us then to determine that the region encompassing two FxFG repeat sequences adopts a disordered but collapsed state. RanBP3 serves here as a prototypical protein that, due to its multiple cysteines, size, and partially disordered structure, is not readily accessible to any of the typical structure determination techniques such as smFRET, NMR, and X-ray crystallography.

Single atom and-molecules chemisorption on solid surfaces

International Nuclear Information System (INIS)

Anda, E.V.; Ure, J.E.; Majlis, N.

1981-01-01

A simplified model for the microscopic interpretation of single atom and- molecules chemisorption on metallic surfaces is presented. An appropriated hamiltonian for this problem is resolved, through the Green's function formalism. (L.C.) [pt

Absolute cross sections from the ''boomerang model'' for resonant electron-molecule scattering

International Nuclear Information System (INIS)

Dube, L.; Herzenberg, A.

1979-01-01

The boomerang model is used to calculate absolute cross sections near the 2 Pi/sub g/ shape resonance in e-N 2 scattering. The calculated cross sections are shown to satisfy detailed balancing. The exchange of electrons is taken into account. A parametrized complex-potential curve for the intermediate N 2 /sup ts-/ ion is determined from a small part of the experimental data, and then used to calculate other properties. The calculations are in good agreement with the absolute cross sections for vibrational excitation from the ground state, the absolute cross section v = 1 → 2, and the absolute total cross section

Temporal and spatial evolution characteristics of disturbance wave in a hypersonic boundary layer due to single-frequency entropy disturbance.

Science.gov (United States)

Wang, Zhenqing; Tang, Xiaojun; Lv, Hongqing; Shi, Jianqiang

2014-01-01

By using a high-order accurate finite difference scheme, direct numerical simulation of hypersonic flow over an 8° half-wedge-angle blunt wedge under freestream single-frequency entropy disturbance is conducted; the generation and the temporal and spatial nonlinear evolution of boundary layer disturbance waves are investigated. Results show that, under the freestream single-frequency entropy disturbance, the entropy state of boundary layer is changed sharply and the disturbance waves within a certain frequency range are induced in the boundary layer. Furthermore, the amplitudes of disturbance waves in the period phase are larger than that in the response phase and ablation phase and the frequency range in the boundary layer in the period phase is narrower than that in these two phases. In addition, the mode competition, dominant mode transformation, and disturbance energy transfer exist among different modes both in temporal and in spatial evolution. The mode competition changes the characteristics of nonlinear evolution of the unstable waves in the boundary layer. The development of the most unstable mode along streamwise relies more on the motivation of disturbance waves in the upstream than that of other modes on this motivation.

Transition paths in single-molecule force spectroscopy.

Science.gov (United States)

Cossio, Pilar; Hummer, Gerhard; Szabo, Attila

2018-03-28

In a typical single-molecule force spectroscopy experiment, the ends of the molecule of interest are connected by long polymer linkers to a pair of mesoscopic beads trapped in the focus of two laser beams. At constant force load, the total extension, i.e., the end-to-end distance of the molecule plus linkers, is measured as a function of time. In the simplest systems, the measured extension fluctuates about two values characteristic of folded and unfolded states, with occasional transitions between them. We have recently shown that molecular (un)folding rates can be recovered from such trajectories, with a small linker correction, as long as the characteristic time of the bead fluctuations is shorter than the residence time in the unfolded (folded) state. Here, we show that accurate measurements of the molecular transition path times require an even faster apparatus response. Transition paths, the trajectory segments in which the molecule (un)folds, are properly resolved only if the beads fluctuate more rapidly than the end-to-end distance of the molecule. Therefore, over a wide regime, the measured rates may be meaningful but not the transition path times. Analytic expressions for the measured mean transition path times are obtained for systems diffusing anisotropically on a two-dimensional free energy surface. The transition path times depend on the properties both of the molecule and of the pulling device.

Simple test system for single molecule recognition force microscopy

International Nuclear Information System (INIS)

Riener, Christian K.; Stroh, Cordula M.; Ebner, Andreas; Klampfl, Christian; Gall, Alex A.; Romanin, Christoph; Lyubchenko, Yuri L.; Hinterdorfer, Peter; Gruber, Hermann J.

2003-01-01

We have established an easy-to-use test system for detecting receptor-ligand interactions on the single molecule level using atomic force microscopy (AFM). For this, avidin-biotin, probably the best characterized receptor-ligand pair, was chosen. AFM sensors were prepared containing tethered biotin molecules at sufficiently low surface concentrations appropriate for single molecule studies. A biotin tether, consisting of a 6 nm poly(ethylene glycol) (PEG) chain and a functional succinimide group at the other end, was newly synthesized and covalently coupled to amine-functionalized AFM tips. In particular, PEG 800 diamine was glutarylated, the mono-adduct NH 2 -PEG-COOH was isolated by ion exchange chromatography and reacted with biotin succinimidylester to give biotin-PEG-COOH which was then activated as N-hydroxysuccinimide (NHS) ester to give the biotin-PEG-NHS conjugate which was coupled to the aminofunctionalized AFM tip. The motional freedom provided by PEG allows for free rotation of the biotin molecule on the AFM sensor and for specific binding to avidin which had been adsorbed to mica surfaces via electrostatic interactions. Specific avidin-biotin recognition events were discriminated from nonspecific tip-mica adhesion by their typical unbinding force (∼40 pN at 1.4 nN/s loading rate), unbinding length (<13 nm), the characteristic nonlinear force-distance relation of the PEG linker, and by specific block with excess of free d-biotin. The convenience of the test system allowed to evaluate, and compare, different methods and conditions of tip aminofunctionalization with respect to specific binding and nonspecific adhesion. It is concluded that this system is well suited as calibration or start-up kit for single molecule recognition force microscopy

Fabrication of Low Noise Borosilicate Glass Nanopores for Single Molecule Sensing.

Directory of Open Access Journals (Sweden)

Jayesh A Bafna

Full Text Available We show low-cost fabrication and characterization of borosilicate glass nanopores for single molecule sensing. Nanopores with diameters of ~100 nm were fabricated in borosilicate glass capillaries using laser assisted glass puller. We further achieve controlled reduction and nanometer-size control in pore diameter by sculpting them under constant electron beam exposure. We successfully fabricate pore diameters down to 6 nm. We next show electrical characterization and low-noise behavior of these borosilicate nanopores and compare their taper geometries. We show, for the first time, a comprehensive characterization of glass nanopore conductance across six-orders of magnitude (1M-1μM of salt conditions, highlighting the role of buffer conditions. Finally, we demonstrate single molecule sensing capabilities of these devices with real-time translocation experiments of individual λ-DNA molecules. We observe distinct current blockage signatures of linear as well as folded DNA molecules as they undergo voltage-driven translocation through the glass nanopores. We find increased signal to noise for single molecule detection for higher trans-nanopore driving voltages. We propose these nanopores will expand the realm of applications for nanopore platform.

Precision analysis for standard deviation measurements of immobile single fluorescent molecule images.

Science.gov (United States)

DeSantis, Michael C; DeCenzo, Shawn H; Li, Je-Luen; Wang, Y M

2010-03-29

Standard deviation measurements of intensity profiles of stationary single fluorescent molecules are useful for studying axial localization, molecular orientation, and a fluorescence imaging system's spatial resolution. Here we report on the analysis of the precision of standard deviation measurements of intensity profiles of single fluorescent molecules imaged using an EMCCD camera.We have developed an analytical expression for the standard deviation measurement error of a single image which is a function of the total number of detected photons, the background photon noise, and the camera pixel size. The theoretical results agree well with the experimental, simulation, and numerical integration results. Using this expression, we show that single-molecule standard deviation measurements offer nanometer precision for a large range of experimental parameters.

The existence of negative absolute temperatures in Axelrod’s social influence model

Science.gov (United States)

Villegas-Febres, J. C.; Olivares-Rivas, W.

2008-06-01

We introduce the concept of temperature as an order parameter in the standard Axelrod’s social influence model. It is defined as the relation between suitably defined entropy and energy functions, T=(. We show that at the critical point, where the order/disorder transition occurs, this absolute temperature changes in sign. At this point, which corresponds to the transition homogeneous/heterogeneous culture, the entropy of the system shows a maximum. We discuss the relationship between the temperature and other properties of the model in terms of cultural traits.

Probing Enzyme-Surface Interactions via Protein Engineering and Single-Molecule Techniques

Science.gov (United States)

2017-06-26

SECURITY CLASSIFICATION OF: The overall objective of this research was to exploit protein engineering and fluorescence single-molecule methods to...enhance our understanding of the interaction of proteins and surfaces. Given this objective, the specific aims of this research were to: 1) exploit the...incorporation of unnatural amino acids in proteins to introduce single-molecule probes (i.e., fluorophores for fluorescence resonance energy transfer

Quantum interference effects at room temperature in OPV-based single-molecule junctions

DEFF Research Database (Denmark)

Arroyo, Carlos R.; Frisenda, Riccardo; Moth-Poulsen, Kasper

2013-01-01

Interference effects on charge transport through an individual molecule can lead to a notable modulation and suppression on its conductance. In this letter, we report the observation of quantum interference effects occurring at room temperature in single-molecule junctions based on oligo(3......)-phenylenevinylene (OPV3) derivatives, in which the central benzene ring is coupled to either para- or meta-positions. Using the break-junction technique, we find that the conductance for a single meta-OPV3 molecule wired between gold electrodes is one order of magnitude smaller than that of a para-OPV3 molecule...

Single-molecule pull-down (SiMPull) for new-age biochemistry: methodology and biochemical applications of single-molecule pull-down (SiMPull) for probing biomolecular interactions in crude cell extracts.

Science.gov (United States)

Aggarwal, Vasudha; Ha, Taekjip

2014-11-01

Macromolecular interactions play a central role in many biological processes. Protein-protein interactions have mostly been studied by co-immunoprecipitation, which cannot provide quantitative information on all possible molecular connections present in the complex. We will review a new approach that allows cellular proteins and biomolecular complexes to be studied in real-time at the single-molecule level. This technique is called single-molecule pull-down (SiMPull), because it integrates principles of conventional immunoprecipitation with the powerful single-molecule fluorescence microscopy. SiMPull is used to count how many of each protein is present in the physiological complexes found in cytosol and membranes. Concurrently, it serves as a single-molecule biochemical tool to perform functional studies on the pulled-down proteins. In this review, we will focus on the detailed methodology of SiMPull, its salient features and a wide range of biological applications in comparison with other biosensing tools. © 2014 WILEY Periodicals, Inc.

Nano- and micro-fabrication for single-molecule biological studies

NARCIS (Netherlands)

Huang, Z.

2012-01-01

Heterogeneity is a general feature in biological system. In order to avoid possible misleading effects of ensemble averaging, and to ensure a correct understanding of the biological system, it is very important to look into individuals, such as a single bio-molecule or a single cell, for details.

Nearest Neighbor Estimates of Entropy for Multivariate Circular Distributions

Directory of Open Access Journals (Sweden)

Neeraj Misra

2010-05-01

Full Text Available In molecular sciences, the estimation of entropies of molecules is important for the understanding of many chemical and biological processes. Motivated by these applications, we consider the problem of estimating the entropies of circular random vectors and introduce non-parametric estimators based on circular distances between n sample points and their k th nearest neighbors (NN, where k (≤ n – 1 is a fixed positive integer. The proposed NN estimators are based on two different circular distances, and are proven to be asymptotically unbiased and consistent. The performance of one of the circular-distance estimators is investigated and compared with that of the already established Euclidean-distance NN estimator using Monte Carlo samples from an analytic distribution of six circular variables of an exactly known entropy and a large sample of seven internal-rotation angles in the molecule of tartaric acid, obtained by a realistic molecular-dynamics simulation.

Fluorescence blinking in MEH-PPV single molecules at low temperature

International Nuclear Information System (INIS)

Mirzov, O.; Cichos, F.; Borczyskowski, C. von; Scheblykin, I.

2005-01-01

Fluorescence intensity transients of single molecules of the conjugated polymer poly[2-methoxy,5-(2'-ethylhexyloxy)-p-phenylene-vinylene] (MEH-PPV) were studied at 15 K. Fluorescence blinking behavior was observed despite the expected low-temperature suppression of energy migration in such disordered molecular systems. Presence of the fluorescence blinking effect at 15 K indicates that the single molecules possess a collapsed conformation with characteristic size of not more than several nanometers, which corresponds to only a few exciton hops over a polymer chain

Radio frequency scanning tunneling spectroscopy for single-molecule spin resonance.

Science.gov (United States)

Müllegger, Stefan; Tebi, Stefano; Das, Amal K; Schöfberger, Wolfgang; Faschinger, Felix; Koch, Reinhold

2014-09-26

We probe nuclear and electron spins in a single molecule even beyond the electromagnetic dipole selection rules, at readily accessible magnetic fields (few mT) and temperatures (5 K) by resonant radio-frequency current from a scanning tunneling microscope. We achieve subnanometer spatial resolution combined with single-spin sensitivity, representing a 10 orders of magnitude improvement compared to existing magnetic resonance techniques. We demonstrate the successful resonant spectroscopy of the complete manifold of nuclear and electronic magnetic transitions of up to ΔI(z)=±3 and ΔJ(z)=±12 of single quantum spins in a single molecule. Our method of resonant radio-frequency scanning tunneling spectroscopy offers, atom-by-atom, unprecedented analytical power and spin control with an impact on diverse fields of nanoscience and nanotechnology.

Mathematical and information-geometrical entropy for phenomenological Fourier and non-Fourier heat conduction

Science.gov (United States)

Li, Shu-Nan; Cao, Bing-Yang

2017-09-01

The second law of thermodynamics governs the direction of heat transport, which provides the foundational definition of thermodynamic Clausius entropy. The definitions of entropy are further generalized for the phenomenological heat transport models in the frameworks of classical irreversible thermodynamics and extended irreversible thermodynamics (EIT). In this work, entropic functions from mathematics are combined with phenomenological heat conduction models and connected to several information-geometrical conceptions. The long-time behaviors of these mathematical entropies exhibit a wide diversity and physical pictures in phenomenological heat conductions, including the tendency to thermal equilibrium, and exponential decay of nonequilibrium and asymptotics, which build a bridge between the macroscopic and microscopic modelings. In contrast with the EIT entropies, the mathematical entropies expressed in terms of the internal energy function can avoid singularity paired with nonpositive local absolute temperature caused by non-Fourier heat conduction models.

Single-Molecule Rotational Switch on a Dangling Bond Dimer Bearing.

Science.gov (United States)

Godlewski, Szymon; Kawai, Hiroyo; Kolmer, Marek; Zuzak, Rafał; Echavarren, Antonio M; Joachim, Christian; Szymonski, Marek; Saeys, Mark

2016-09-27

One of the key challenges in the construction of atomic-scale circuits and molecular machines is to design molecular rotors and switches by controlling the linear or rotational movement of a molecule while preserving its intrinsic electronic properties. Here, we demonstrate both the continuous rotational switching and the controlled step-by-step single switching of a trinaphthylene molecule adsorbed on a dangling bond dimer created on a hydrogen-passivated Ge(001):H surface. The molecular switch is on-surface assembled when the covalent bonds between the molecule and the dangling bond dimer are controllably broken, and the molecule is attached to the dimer by long-range van der Waals interactions. In this configuration, the molecule retains its intrinsic electronic properties, as confirmed by combined scanning tunneling microscopy/spectroscopy (STM/STS) measurements, density functional theory calculations, and advanced STM image calculations. Continuous switching of the molecule is initiated by vibronic excitations when the electrons are tunneling through the lowest unoccupied molecular orbital state of the molecule. The switching path is a combination of a sliding and rotation motion over the dangling bond dimer pivot. By carefully selecting the STM conditions, control over discrete single switching events is also achieved. Combined with the ability to create dangling bond dimers with atomic precision, the controlled rotational molecular switch is expected to be a crucial building block for more complex surface atomic-scale devices.

High spin cycles: topping the spin record for a single molecule verging on quantum criticality

Science.gov (United States)

Baniodeh, Amer; Magnani, Nicola; Lan, Yanhua; Buth, Gernot; Anson, Christopher E.; Richter, Johannes; Affronte, Marco; Schnack, Jürgen; Powell, Annie K.

2018-03-01

The cyclisation of a short chain into a ring provides fascinating scenarios in terms of transforming a finite array of spins into a quasi-infinite structure. If frustration is present, theory predicts interesting quantum critical points, where the ground state and thus low-temperature properties of a material change drastically upon even a small variation of appropriate external parameters. This can be visualised as achieving a very high and pointed summit where the way down has an infinity of possibilities, which by any parameter change will be rapidly chosen, in order to reach the final ground state. Here we report a mixed 3d/4f cyclic coordination cluster that turns out to be very near or even at such a quantum critical point. It has a ground state spin of S = 60, the largest ever observed for a molecule (120 times that of a single electron). [Fe10Gd10(Me-tea)10(Me-teaH)10(NO3)10].20MeCN forms a nano-torus with alternating gadolinium and iron ions with a nearest neighbour Fe-Gd coupling and a frustrating next-nearest neighbour Fe-Fe coupling. Such a spin arrangement corresponds to a cyclic delta or saw-tooth chain, which can exhibit unusual frustration effects. In the present case, the quantum critical point bears a `flatland' of tens of thousands of energetically degenerate states between which transitions are possible at no energy costs with profound caloric consequences. Entropy-wise the energy flatland translates into the pointed summit overlooking the entropy landscape. Going downhill several target states can be reached depending on the applied physical procedure which offers new prospects for addressability.

Current rectification in a single molecule diode: the role of electrode coupling.

Science.gov (United States)

Sherif, Siya; Rubio-Bollinger, Gabino; Pinilla-Cienfuegos, Elena; Coronado, Eugenio; Cuevas, Juan Carlos; Agraït, Nicolás

2015-07-24

We demonstrate large rectification ratios (> 100) in single-molecule junctions based on a metal-oxide cluster (polyoxometalate), using a scanning tunneling microscope (STM) both at ambient conditions and at low temperature. These rectification ratios are the largest ever observed in a single-molecule junction, and in addition these junctions sustain current densities larger than 10(5) A cm(-2). By following the variation of the I-V characteristics with tip-molecule separation we demonstrate unambiguously that rectification is due to asymmetric coupling to the electrodes of a molecule with an asymmetric level structure. This mechanism can be implemented in other type of molecular junctions using both organic and inorganic molecules and provides a simple strategy for the rational design of molecular diodes.

Thermophoretic forces on DNA measured with a single-molecule spring balance

DEFF Research Database (Denmark)

Pedersen, Jonas Nyvold; Lüscher, Christopher James; Marie, Rodolphe

2014-01-01

We stretch a single DNA molecule with thermophoretic forces and measure these forces with a spring balance: the DNA molecule itself. It is an entropic spring which we calibrate, using as a benchmark its Brownian motion in the nanochannel that contains and prestretches it. This direct measurement ....... We find the Soret coefficient per unit length of DNA at various ionic strengths. It agrees, with novel precision, with results obtained in bulk for DNA too short to shield itself and with the thermodynamic model of thermophoresis.......We stretch a single DNA molecule with thermophoretic forces and measure these forces with a spring balance: the DNA molecule itself. It is an entropic spring which we calibrate, using as a benchmark its Brownian motion in the nanochannel that contains and prestretches it. This direct measurement...

Experimental and Computational Characterization of Biological Liquid Crystals: A Review of Single-Molecule Bioassays

Directory of Open Access Journals (Sweden)

Sungsoo Na

2009-09-01

Full Text Available Quantitative understanding of the mechanical behavior of biological liquid crystals such as proteins is essential for gaining insight into their biological functions, since some proteins perform notable mechanical functions. Recently, single-molecule experiments have allowed not only the quantitative characterization of the mechanical behavior of proteins such as protein unfolding mechanics, but also the exploration of the free energy landscape for protein folding. In this work, we have reviewed the current state-of-art in single-molecule bioassays that enable quantitative studies on protein unfolding mechanics and/or various molecular interactions. Specifically, single-molecule pulling experiments based on atomic force microscopy (AFM have been overviewed. In addition, the computational simulations on single-molecule pulling experiments have been reviewed. We have also reviewed the AFM cantilever-based bioassay that provides insight into various molecular interactions. Our review highlights the AFM-based single-molecule bioassay for quantitative characterization of biological liquid crystals such as proteins.

Nonequilibrium Chemical Effects in Single-Molecule SERS Revealed by Ab Initio Molecular Dynamics Simulations

Energy Technology Data Exchange (ETDEWEB)

Fischer, Sean A.; Apra, Edoardo; Govind, Niranjan; Hess, Wayne P.; El-Khoury, Patrick Z.

2017-02-03

Recent developments in nanophotonics have paved the way for achieving significant advances in the realm of single molecule chemical detection, imaging, and dynamics. In particular, surface-enhanced Raman scattering (SERS) is a powerful analytical technique that is now routinely used to identify the chemical identity of single molecules. Understanding how nanoscale physical and chemical processes affect single molecule SERS spectra and selection rules is a challenging task, and is still actively debated. Herein, we explore underappreciated chemical phenomena in ultrasensitive SERS. We observe a fluctuating excited electronic state manifold, governed by the conformational dynamics of a molecule (4,4’-dimercaptostilbene, DMS) interacting with a metallic cluster (Ag20). This affects our simulated single molecule SERS spectra; the time trajectories of a molecule interacting with its unique local environment dictates the relative intensities of the observable Raman-active vibrational states. Ab initio molecular dynamics of a model Ag20-DMS system are used to illustrate both concepts in light of recent experimental results.

SpatEntropy: Spatial Entropy Measures in R

OpenAIRE

Altieri, Linda; Cocchi, Daniela; Roli, Giulia

2018-01-01

This article illustrates how to measure the heterogeneity of spatial data presenting a finite number of categories via computation of spatial entropy. The R package SpatEntropy contains functions for the computation of entropy and spatial entropy measures. The extension to spatial entropy measures is a unique feature of SpatEntropy. In addition to the traditional version of Shannon's entropy, the package includes Batty's spatial entropy, O'Neill's entropy, Li and Reynolds' contagion index, Ka...

Entropy Production in Pipeline Flow of Dispersions of Water in Oil

Directory of Open Access Journals (Sweden)

Rajinder Pal

2014-08-01

Full Text Available Entropy production in pipeline adiabatic flow of water-in-oil emulsions is investigated experimentally in three different diameter pipes. The dispersed-phase (water droplets concentration of emulsion is varied from 0 to 41% vol. The entropy production rates in emulsion flow are compared with the values expected in single-phase flow of Newtonian fluids with the same properties (viscosity and density. While in the laminar regime the entropy production rates in emulsion flow can be described adequately by the single-phase Newtonian equations, a significant deviation from single-phase flow behavior is observed in the turbulent regime. In the turbulent regime, the entropy production rates in emulsion flow are found to be substantially smaller than those expected on the basis of single-phase equations. For example, the entropy production rate in water-in-oil emulsion flow at a dispersed-phase volume fraction of 0.41 is only 38.4% of that observed in flow of a single-phase Newtonian fluid with the same viscosity and density, when comparison is made at a Reynolds number of 4000. Thus emulsion flow in pipelines is more efficient thermodynamically than single-phase Newtonian flow.

Towards Controlled Single-Molecule Manipulation Using “Real-Time” Molecular Dynamics Simulation: A GPU Implementation

Directory of Open Access Journals (Sweden)

Dyon van Vreumingen

2018-05-01

Full Text Available Molecular electronics saw its birth with the idea to build electronic circuitry with single molecules as individual components. Even though commercial applications are still modest, it has served an important part in the study of fundamental physics at the scale of single atoms and molecules. It is now a routine procedure in many research groups around the world to connect a single molecule between two metallic leads. What is unknown is the nature of this coupling between the molecule and the leads. We have demonstrated recently (Tewari, 2018, Ph.D. Thesis our new setup based on a scanning tunneling microscope, which can be used to controllably manipulate single molecules and atomic chains. In this article, we will present the extension of our molecular dynamic simulator attached to this system for the manipulation of single molecules in real time using a graphics processing unit (GPU. This will not only aid in controlled lift-off of single molecules, but will also provide details about changes in the molecular conformations during the manipulation. This information could serve as important input for theoretical models and for bridging the gap between the theory and experiments.

Single-Molecule Stochastic Resonance

Directory of Open Access Journals (Sweden)

K. Hayashi

2012-08-01

Full Text Available Stochastic resonance (SR is a well-known phenomenon in dynamical systems. It consists of the amplification and optimization of the response of a system assisted by stochastic (random or probabilistic noise. Here we carry out the first experimental study of SR in single DNA hairpins which exhibit cooperatively transitions from folded to unfolded configurations under the action of an oscillating mechanical force applied with optical tweezers. By varying the frequency of the force oscillation, we investigate the folding and unfolding kinetics of DNA hairpins in a periodically driven bistable free-energy potential. We measure several SR quantifiers under varied conditions of the experimental setup such as trap stiffness and length of the molecular handles used for single-molecule manipulation. We find that a good quantifier of the SR is the signal-to-noise ratio (SNR of the spectral density of measured fluctuations in molecular extension of the DNA hairpins. The frequency dependence of the SNR exhibits a peak at a frequency value given by the resonance-matching condition. Finally, we carry out experiments on short hairpins that show how SR might be useful for enhancing the detection of conformational molecular transitions of low SNR.

Single Molecule Screening of Disease DNA Without Amplification

Energy Technology Data Exchange (ETDEWEB)

Lee, Ji-Young [Iowa State Univ., Ames, IA (United States)

2006-01-01

The potential of single molecule detection as an analysis tool in biological and medical fields is well recognized today. This fast evolving technique will provide fundamental sensitivity to pick up individual pathogen molecules, and therefore contribute to a more accurate diagnosis and a better chance for a complete cure. Many studies are being carried out to successfully apply this technique in real screening fields. In this dissertation, several attempts are shown that have been made to test and refine the application of the single molecule technique as a clinical screening method. A basic applicability was tested with a 100% target content sample, using electrophoretic mobility and multiple colors as identification tools. Both electrophoretic and spectral information of individual molecule were collected within a second, while the molecule travels along the flow in a capillary. Insertion of a transmission grating made the recording of the whole spectrum of a dye-stained molecule possible without adding complicated instrumental components. Collecting two kinds of information simultaneously and combining them allowed more thorough identification, up to 98.8% accuracy. Probing mRNA molecules with fluorescently labeled cDNA via hybridization was also carried out. The spectral differences among target, probe, and hybrid were interpreted in terms of dispersion distances after transmission grating, and used for the identification of each molecule. The probes were designed to have the least background when they are free, but have strong fluorescence after hybridization via fluorescence resonance energy transfer. The mRNA-cDNA hybrids were further imaged in whole blood, plasma, and saliva, to test how far a crude preparation can be tolerated. Imaging was possible with up to 50% of clear bio-matrix contents, suggesting a simple lysis and dilution would be sufficient for imaging for some cells. Real pathogen DNA of human papillomavirus (HPV) type-I6 in human genomic DNA

Black hole entropy in the O(N) model

International Nuclear Information System (INIS)

Kabat, D.; Shenker, S.H.; Strassler, M.J.

1995-01-01

We consider corrections to the entropy of a black hole from an O(N)-invariant linear σ model. We obtain the entropy from a 1/N expansion of the partition function on a cone. The entropy arises from diagrams which are analogous to those introduced by Susskind and Uglum to explain black hole entropy in string theory. The interpretation of the σ-model entropy depends on scale. At short distances, it has a state counting interpretation, as the entropy of entanglement of the N fields φ a . In the infrared, the effective theory has a single composite field σ∼φ a φ a , and the state counting interpretation of the entropy is lost. copyright 1995 The American Physical Society

Adjoint entropy vs topological entropy

OpenAIRE

Giordano Bruno, Anna

2012-01-01

Recently the adjoint algebraic entropy of endomorphisms of abelian groups was introduced and studied. We generalize the notion of adjoint entropy to continuous endomorphisms of topological abelian groups. Indeed, the adjoint algebraic entropy is defined using the family of all finite-index subgroups, while we take only the subfamily of all open finite-index subgroups to define the topological adjoint entropy. This allows us to compare the (topological) adjoint entropy with the known topologic...

Fluorescence single-molecule counting assays for protein quantification using epi-fluorescence microscopy with quantum dots labeling

International Nuclear Information System (INIS)

Jiang Dafeng; Liu Chunxia; Wang Lei; Jiang Wei

2010-01-01

A single-molecule counting approach for quantifying the antibody affixed to a surface using quantum dots and epi-fluorescence microscopy is presented. Modifying the glass substrates with carboxyl groups provides a hydrophilic surface that reacts with amine groups of an antibody to allow covalent immobilization of the antibody. Nonspecific adsorption of single molecules on the modified surfaces was first investigated. Then, quantum dots were employed to form complexes with surface-immobilized antibody molecules and used as fluorescent probes for single-molecule imaging. Epi-fluorescence microscopy was chosen as the tool for single-molecule fluorescence detection here. The generated fluorescence signals were taken by an electron multiplying charge-coupled device and were found to be proportional to the sample concentrations. Under optimal conditions, a linear response range of 5.0 x 10 -14 -3.0 x 10 -12 mol L -1 was obtained between the number of single molecules and sample concentration via a single-molecule counting approach.

Coupling single-molecule magnets to quantum circuits

International Nuclear Information System (INIS)

Jenkins, Mark; Martínez-Pérez, María José; Zueco, David; Luis, Fernando; Hümmer, Thomas; García-Ripoll, Juanjo

2013-01-01

In this work we study theoretically the coupling of single-molecule magnets (SMMs) to a variety of quantum circuits, including microwave resonators with and without constrictions and flux qubits. The main result of this study is that it is possible to achieve strong and ultrastrong coupling regimes between SMM crystals and the superconducting circuit, with strong hints that such a coupling could also be reached for individual molecules close to constrictions. Building on the resulting coupling strengths and the typical coherence times of these molecules (∼ μs), we conclude that SMMs can be used for coherent storage and manipulation of quantum information, either in the context of quantum computing or in quantum simulations. Throughout the work we also discuss in detail the family of molecules that are most suitable for such operations, based not only on the coupling strength, but also on the typical energy gaps and the simplicity with which they can be tuned and oriented. Finally, we also discuss practical advantages of SMMs, such as the possibility to fabricate the SMMs ensembles on the chip through the deposition of small droplets. (paper)

Large entropy derived from low-frequency vibrations and its implications for hydrogen storage

Science.gov (United States)

Wang, Xiaoxia; Chen, Hongshan

2018-02-01

Adsorption and desorption are driven by the energy and entropy competition, but the entropy effect is often ignored in hydrogen storage and the optimal adsorption strength for the ambient storage is controversial in the literature. This letter investigated the adsorption states of the H2 molecule on M-B12C6N6 (M = Li, Na, Mg, Ca, and Sc) and analyzed the correlation among the zero point energy (ZPE), the entropy change, and the adsorption energy and their effects on the delivery capacities. The ZPE has large correction to the adsorption energy due to the light mass of hydrogen. The computations show that the potential energies along the spherical surface centered at the alkali metals are very flat and it leads to large entropy (˜70 J/mol.K) of the adsorbed H2 molecules. The entropy change can compensate the enthalpy change effectively, and the ambient storage can be realized with relatively weak adsorption of ΔH = -12 kJ/mol. The results are encouraging and instructive for the design of hydrogen storage materials.

Conducting single-molecule magnet materials.

Science.gov (United States)

Cosquer, Goulven; Shen, Yongbing; Almeida, Manuel; Yamashita, Masahiro

2018-05-11

Multifunctional molecular materials exhibiting electrical conductivity and single-molecule magnet (SMM) behaviour are particularly attractive for electronic devices and related applications owing to the interaction between electronic conduction and magnetization of unimolecular units. The preparation of such materials remains a challenge that has been pursued by a bi-component approach of combination of SMM cationic (or anionic) units with conducting networks made of partially oxidized (or reduced) donor (or acceptor) molecules. The present status of the research concerning the preparation of molecular materials exhibiting SMM behaviour and electrical conductivity is reviewed, describing the few molecular compounds where both SMM properties and electrical conductivity have been observed. The evolution of this research field through the years is discussed. The first reported compounds are semiconductors in spite being able to present relatively high electrical conductivity, and the SMM behaviour is observed at low temperatures where the electrical conductivity of the materials is similar to that of an insulator. During the recent years, a breakthrough has been achieved with the coexistence of high electrical conductivity and SMM behaviour in a molecular compound at the same temperature range, but so far without evidence of a synergy between these properties. The combination of high electrical conductivity with SMM behaviour requires not only SMM units but also the regular and as far as possible uniform packing of partially oxidized molecules, which are able to provide a conducting network.

Spin-Spin Cross Relaxation in Single-Molecule Magnets

Science.gov (United States)

Wernsdorfer, W.; Bhaduri, S.; Tiron, R.; Hendrickson, D. N.; Christou, G.

2002-10-01

The one-body tunnel picture of single-molecule magnets (SMMs) is not always sufficient to explain the measured tunnel transitions. An improvement to the picture is proposed by including also two-body tunnel transitions such as spin-spin cross relaxation (SSCR) which are mediated by dipolar and weak superexchange interactions between molecules. A Mn4 SMM is used as a model system. At certain external fields, SSCRs lead to additional quantum resonances which show up in hysteresis loop measurements as well-defined steps. A simple model is used to explain quantitatively all observed transitions.

Entangled photons from single atoms and molecules

Science.gov (United States)

Nordén, Bengt

2018-05-01

The first two-photon entanglement experiment performed 50 years ago by Kocher and Commins (KC) provided isolated pairs of entangled photons from an atomic three-state fluorescence cascade. In view of questioning of Bell's theorem, data from these experiments are re-analyzed and shown sufficiently precise to confirm quantum mechanical and dismiss semi-classical theory without need for Bell's inequalities. Polarization photon correlation anisotropy (A) is useful: A is near unity as predicted quantum mechanically and well above the semi-classic range, 0 ⩽ A ⩽ 1 / 2 . Although yet to be found, one may envisage a three-state molecule emitting entangled photon pairs, in analogy with the KC atomic system. Antibunching in fluorescence from single molecules in matrix and entangled photons from quantum dots promise it be possible. Molecules can have advantages to parametric down-conversion as the latter photon distribution is Poissonian and unsuitable for producing isolated pairs of entangled photons. Analytical molecular applications of entangled light are also envisaged.

Assembly and diploid architecture of an individual human genome via single-molecule technologies.

Science.gov (United States)

Pendleton, Matthew; Sebra, Robert; Pang, Andy Wing Chun; Ummat, Ajay; Franzen, Oscar; Rausch, Tobias; Stütz, Adrian M; Stedman, William; Anantharaman, Thomas; Hastie, Alex; Dai, Heng; Fritz, Markus Hsi-Yang; Cao, Han; Cohain, Ariella; Deikus, Gintaras; Durrett, Russell E; Blanchard, Scott C; Altman, Roger; Chin, Chen-Shan; Guo, Yan; Paxinos, Ellen E; Korbel, Jan O; Darnell, Robert B; McCombie, W Richard; Kwok, Pui-Yan; Mason, Christopher E; Schadt, Eric E; Bashir, Ali

2015-08-01

We present the first comprehensive analysis of a diploid human genome that combines single-molecule sequencing with single-molecule genome maps. Our hybrid assembly markedly improves upon the contiguity observed from traditional shotgun sequencing approaches, with scaffold N50 values approaching 30 Mb, and we identified complex structural variants (SVs) missed by other high-throughput approaches. Furthermore, by combining Illumina short-read data with long reads, we phased both single-nucleotide variants and SVs, generating haplotypes with over 99% consistency with previous trio-based studies. Our work shows that it is now possible to integrate single-molecule and high-throughput sequence data to generate de novo assembled genomes that approach reference quality.

Upper entropy axioms and lower entropy axioms

International Nuclear Information System (INIS)

Guo, Jin-Li; Suo, Qi

2015-01-01

The paper suggests the concepts of an upper entropy and a lower entropy. We propose a new axiomatic definition, namely, upper entropy axioms, inspired by axioms of metric spaces, and also formulate lower entropy axioms. We also develop weak upper entropy axioms and weak lower entropy axioms. Their conditions are weaker than those of Shannon–Khinchin axioms and Tsallis axioms, while these conditions are stronger than those of the axiomatics based on the first three Shannon–Khinchin axioms. The subadditivity and strong subadditivity of entropy are obtained in the new axiomatics. Tsallis statistics is a special case of satisfying our axioms. Moreover, different forms of information measures, such as Shannon entropy, Daroczy entropy, Tsallis entropy and other entropies, can be unified under the same axiomatics

Connecting diffusion and entropy of bulk water at the single particle ...

Indian Academy of Sciences (India)

The relation between the dynamic (e.g., diffusion) and thermodynamic (e.g., entropy) properties of water and water-like liquids has been an active area of research for a long time. Although several studies have investigated the diffusivity and entropy for different systems, these studies have probed either the configurational ...

Visualizing Single-molecule DNA Replication with Fluorescence Microscopy

NARCIS (Netherlands)

Tanner, Nathan A.; Loparo, Joseph J.; Oijen, Antoine M. van

2009-01-01

We describe a simple fluorescence microscopy-based real-time method for observing DNA replication at the single-molecule level. A circular, forked DNA template is attached to a functionalized glass coverslip and replicated extensively after introduction of replication proteins and nucleotides. The

Configurational entropy of hydrogen-disordered ice polymorphs

International Nuclear Information System (INIS)

Herrero, Carlos P.; Ramírez, Rafael

2014-01-01

The configurational entropy of several H-disordered ice polymorphs is calculated by means of a thermodynamic integration along a path between a totally H-disordered state and one fulfilling the Bernal-Fowler ice rules. A Monte Carlo procedure based on a simple energy model is used, so that the employed thermodynamic path drives the system from high temperatures to the low-temperature limit. This method turns out to be precise enough to give reliable values for the configurational entropy s th of different ice phases in the thermodynamic limit (number of molecules N → ∞). The precision of the method is checked for the ice model on a two-dimensional square lattice. Results for the configurational entropy are given for H-disordered arrangements on several polymorphs, including ices Ih, Ic, II, III, IV, V, VI, and XII. The highest and lowest entropy values correspond to ices VI and XII, respectively, with a difference of 3.3% between them. The dependence of the entropy on the ice structures has been rationalized by comparing it with structural parameters of the various polymorphs, such as the mean ring size. A particularly good correlation has been found between the configurational entropy and the connective constant derived from self-avoiding walks on the ice networks

Electric-Field Control of Interfering Transport Pathways in a Single-Molecule Anthraquinone Transistor

NARCIS (Netherlands)

Koole, Max; Thijssen, Jos M.; Valkenier, Hennie; Hummelen, Jan C.; van der Zant, Herre S. J.

It is understood that molecular conjugation plays an important role in charge transport through single-molecule junctions. Here, we investigate electron transport through an anthraquinone based single-molecule three-terminal device. With the use of an electric-field induced by a gate electrode, the

Nonsymmetric entropy and maximum nonsymmetric entropy principle

International Nuclear Information System (INIS)

Liu Chengshi

2009-01-01

Under the frame of a statistical model, the concept of nonsymmetric entropy which generalizes the concepts of Boltzmann's entropy and Shannon's entropy, is defined. Maximum nonsymmetric entropy principle is proved. Some important distribution laws such as power law, can be derived from this principle naturally. Especially, nonsymmetric entropy is more convenient than other entropy such as Tsallis's entropy in deriving power laws.

Thermoeconomic diagnosis and entropy generation paradox

DEFF Research Database (Denmark)

Sigthorsson, Oskar; Ommen, Torben Schmidt; Elmegaard, Brian

2017-01-01

In the entropy generation paradox, the entropy generation number, as a function of heat exchanger effectiveness, counter-intuitively approaches zero in two limits symmetrically from a single maximum. In thermoeconomic diagnosis, namely in the characteristic curve method, the exergy destruction...... to the entropy generation paradox, as a decreased heat exchanger effectiveness (as in the case of an operation anomaly in the component) can counter-intuitively result in decreased exergy destruction rate of the component. Therefore, along with an improper selection of independent variables, the heat exchanger...... increases in case of an operation anomaly in a component. The normalised exergy destruction rate as the dependent variable therefore resolves the relation of the characteristic curve method with the entropy generation paradox....

DNA Origami Directed Au Nanostar Dimers for Single-Molecule Surface-Enhanced Raman Scattering.

Science.gov (United States)

Tanwar, Swati; Haldar, Krishna Kanta; Sen, Tapasi

2017-12-06

We demonstrate the synthesis of Au nanostar dimers with tunable interparticle gap and controlled stoichiometry assembled on DNA origami. Au nanostars with uniform and sharp tips were immobilized on rectangular DNA origami dimerized structures to create nanoantennas containing monomeric and dimeric Au nanostars. Single Texas red (TR) dye was specifically attached in the junction of the dimerized origami to act as a Raman reporter molecule. The SERS enhancement factors of single TR dye molecules located in the conjunction region in dimer structures having interparticle gaps of 7 and 13 nm are 2 × 10 10 and 8 × 10 9 , respectively, which are strong enough for single analyte detection. The highly enhanced electromagnetic field generated by the plasmon coupling between sharp tips and cores of two Au nanostars in the wide conjunction region allows the accommodation and specific detection of large biomolecules. Such DNA-directed assembled nanoantennas with controlled interparticle separation distance and stoichiometry, and well-defined geometry, can be used as excellent substrates in single-molecule SERS spectroscopy and will have potential applications as a reproducible platform in single-molecule sensing.

Critical study on conventional concept of entropy

International Nuclear Information System (INIS)

Afridi, M.K.; Nizami, S.

2006-01-01

The concept of increase in entropy or disorder as a result of all natural processes has been critically reviewed on the basis of experimental facts and ongoing phenomena on our Globe. Similarly, order-disorder statements have also been judged under new and fresh look. In fact, these are not absolute but depend upon defining specific purpose and considering that whether that purpose is being served or not. The new concept has been elaborated by considering natural biological processes, spontaneous mixing of four different gases, distribution of four points in space and assembling of a packaged electronic gadget. Actually, this order-disorder dilemma is the result of not defining the specific purpose of a process which leads to so-called concept that disorder is increasing day by day in our universe. The traditional concept of entropy has been finally tested under heat exchange and probability considerations, which also yield no information to discern it as a measure of disorder. Consequently, increase of entropy translating into increase of disorder could not be applied to all natural processes especially the natural biological systems. (author)

Computing magnetic anisotropy constants of single molecule magnets

Indian Academy of Sciences (India)

We present here a theoretical approach to compute the molecular magnetic anisotropy parameters, and for single molecule magnets in any given spin eigenstate of exchange spin Hamiltonian. We first describe a hybrid constant -valence bond (VB) technique of solving spin Hamiltonians employing full spatial ...

Single molecule tools for enzymology, structural biology, systems biology and nanotechnology: an update

Science.gov (United States)

Widom, Julia R.; Dhakal, Soma; Heinicke, Laurie A.; Walter, Nils G.

2015-01-01

Toxicology is the highly interdisciplinary field studying the adverse effects of chemicals on living organisms. It requires sensitive tools to detect such effects. After their initial implementation during the 1990s, single-molecule fluorescence detection tools were quickly recognized for their potential to contribute greatly to many different areas of scientific inquiry. In the intervening time, technical advances in the field have generated ever-improving spatial and temporal resolution, and have enabled the application of single-molecule fluorescence to increasingly complex systems, such as live cells. In this review, we give an overview of the optical components necessary to implement the most common versions of single-molecule fluorescence detection. We then discuss current applications to enzymology and structural studies, systems biology, and nanotechnology, presenting the technical considerations that are unique to each area of study, along with noteworthy recent results. We also highlight future directions that have the potential to revolutionize these areas of study by further exploiting the capabilities of single-molecule fluorescence microscopy. PMID:25212907

Linear entropy and collapse–revival phenomenon for a general formalism N-type four-level atom interacting with a single-mode field

Science.gov (United States)

Eied, A. A.

2018-05-01

In this paper, the linear entropy and collapse-revival phenomenon through the relation ( -{\\bar{n}}) in a system of N-configuration four-level atom interacting with a single-mode field with additional forms of nonlinearities of both the field and the intensity-dependent atom-field coupling functional are investigated. A factorization of the initial density operator is assumed, considering the field to be initially in a squeezed coherent states and the atom initially in its most upper excited state. The dynamical behavior of the linear entropy and the time evolution of ( -{\\bar{n}}) are analyzed. In particular, the effects of the mean photon number, detuning, Kerr-like medium and the intensity-dependent coupling functional on the entropy and the evolution of ( -{\\bar{n}}) are examined.

Proposal for probing energy transfer pathway by single-molecule pump-dump experiment

OpenAIRE

Tao, Ming-Jie; Ai, Qing; Deng, Fu-Guo; Cheng, Yuan-Chung

2016-01-01

The structure of Fenna-Matthews-Olson (FMO) light-harvesting complex has long been recognized as containing seven bacteriochlorophyll (BChl) molecules. Recently, an additional BChl molecule was discovered in the crystal structure of the FMO complex, which may serve as a link between baseplate and the remaining seven molecules. Here, we investigate excitation energy transfer (EET) process by simulating single-molecule pump-dump experiment in the eight-molecules complex. We adopt the coherent m...

Ultrafast single-molecule photonics: Excited state dynamics in coherently coupled complexes

International Nuclear Information System (INIS)

Hernando, Jordi; Hoogenboom, Jacob; Dijk, Erik van; Garcia-Parajo, Maria; Hulst, Niek F. van

2008-01-01

We present a single-molecule study on femtosecond dynamics in multichromophoric systems, combining fs pump-probe, emission-spectra and fluorescence-lifetime analysis. The ultrafast fs approach gives direct information on the initial exciton dynamics after excitation. The lifetime data show superradiance, a direct measure for the extent of the coherent coupling and static disorder. The spectra finally reveal the role of exciton-phonon coupling. At the single-molecule level a wide range of exciton delocalization lengths and energy redistribution times is revealed

Ultrafast single-molecule photonics: Excited state dynamics in coherently coupled complexes

Energy Technology Data Exchange (ETDEWEB)

Hernando, Jordi [Dept. de Quimica, Universitat Autonoma Barcelona, 08193 Cerdanyola del Valles (Spain); Hoogenboom, Jacob [ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860 Castelldefels, Barcelona (Spain); Dijk, Erik van [Applied Optics Group, MESA Institute for Nanotechnology, University of Twente, 7500AE Enschede (Netherlands); Garcia-Parajo, Maria [IBEC-Institute of BioEngineering of Catalunya, 08028 Barcelona (Spain); ICREA-Institucio Catalana de Recerca i Estudis Avancats, 08015 Barcelona (Spain); Hulst, Niek F. van [ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860 Castelldefels, Barcelona (Spain) and ICREA-Institucio Catalana de Recerca i Estudis Avancats, 08015 Barcelona (Spain)], E-mail: Niek.vanHulst@ICFO.es

2008-05-15

We present a single-molecule study on femtosecond dynamics in multichromophoric systems, combining fs pump-probe, emission-spectra and fluorescence-lifetime analysis. The ultrafast fs approach gives direct information on the initial exciton dynamics after excitation. The lifetime data show superradiance, a direct measure for the extent of the coherent coupling and static disorder. The spectra finally reveal the role of exciton-phonon coupling. At the single-molecule level a wide range of exciton delocalization lengths and energy redistribution times is revealed.

SINGLE MOLECULE APPROACHES TO BIOLOGY, 2010 GORDON RESEARCH CONFERENCE, JUNE 27-JULY 2, 2010, ITALY

Energy Technology Data Exchange (ETDEWEB)

Professor William Moerner

2010-07-09

The 2010 Gordon Conference on Single-Molecule Approaches to Biology focuses on cutting-edge research in single-molecule science. Tremendous technical developments have made it possible to detect, identify, track, and manipulate single biomolecules in an ambient environment or even in a live cell. Single-molecule approaches have changed the way many biological problems are addressed, and new knowledge derived from these approaches continues to emerge. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of biomolecular machines: what they do, how they work individually, how they work together, and finally, how they work inside live cells. The burgeoning use of single-molecule methods to elucidate biological problems is a highly multidisciplinary pursuit, involving both force- and fluorescence-based methods, the most up-to-date advances in microscopy, innovative biological and chemical approaches, and nanotechnology tools. This conference seeks to bring together top experts in molecular and cell biology with innovators in the measurement and manipulation of single molecules, and will provide opportunities for junior scientists and graduate students to present their work in poster format and to exchange ideas with leaders in the field. A number of excellent poster presenters will be selected for short oral talks. Topics as diverse as single-molecule sequencing, DNA/RNA/protein interactions, folding machines, cellular biophysics, synthetic biology and bioengineering, force spectroscopy, new method developments, superresolution imaging in cells, and novel probes for single-molecule imaging will be on the program. Additionally, the collegial atmosphere of this Conference, with programmed discussion sessions as well as opportunities for informal gatherings in the afternoons and evenings in the beauty of the Il Ciocco site in

Entropy, neutro-entropy and anti-entropy for neutrosophic information

OpenAIRE

Vasile Patrascu

2017-01-01

This approach presents a multi-valued representation of the neutrosophic information. It highlights the link between the bifuzzy information and neutrosophic one. The constructed deca-valued structure shows the neutrosophic information complexity. This deca-valued structure led to construction of two new concepts for the neutrosophic information: neutro-entropy and anti-entropy. These two concepts are added to the two existing: entropy and non-entropy. Thus, we obtained the following triad: e...

Extracting physics of life at the molecular level: A review of single-molecule data analyses.

Science.gov (United States)

Colomb, Warren; Sarkar, Susanta K

2015-06-01

Studying individual biomolecules at the single-molecule level has proved very insightful recently. Single-molecule experiments allow us to probe both the equilibrium and nonequilibrium properties as well as make quantitative connections with ensemble experiments and equilibrium thermodynamics. However, it is important to be careful about the analysis of single-molecule data because of the noise present and the lack of theoretical framework for processes far away from equilibrium. Biomolecular motion, whether it is free in solution, on a substrate, or under force, involves thermal fluctuations in varying degrees, which makes the motion noisy. In addition, the noise from the experimental setup makes it even more complex. The details of biologically relevant interactions, conformational dynamics, and activities are hidden in the noisy single-molecule data. As such, extracting biological insights from noisy data is still an active area of research. In this review, we will focus on analyzing both fluorescence-based and force-based single-molecule experiments and gaining biological insights at the single-molecule level. Inherently nonequilibrium nature of biological processes will be highlighted. Simulated trajectories of biomolecular diffusion will be used to compare and validate various analysis techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

An exploration for the macroscopic physical meaning of entropy

Institute of Scientific and Technical Information of China (English)

无

2010-01-01

The macroscopic physical meaning of entropy is analyzed based on the exergy (availability) of a combined system (a closed system and its environment), which is the maximum amount of useful work obtainable from the system and the environment as the system is brought into equilibrium with the environment. The process the system experiences can be divided in two sequent sub-processes, the process at constant volume, which represents the heat interaction of the system with the environment, and the adiabatic process, which represents the work interaction of the system with the environment. It is shown that the macroscopic physical meaning of entropy is a measure of the unavailable energy of a closed system for doing useful work through heat interaction. This statement is more precise than those reported in prior literature. The unavailability function of a closed system can be defined as T0S and p0V in volume constant process and adiabatic process, respectively. Their changes, that is, AiTgS) and A (p0V) represent the unusable parts of the internal energy of a closed system for doing useful work in corresponding processes. Finally, the relation between Clausius entropy and Boltzmann entropy is discussed based on the comparison of their expressions for absolute entropy.

Physical entropy, information entropy and their evolution equations

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

Inspired by the evolution equation of nonequilibrium statistical physics entropy and the concise statistical formula of the entropy production rate, we develop a theory of the dynamic information entropy and build a nonlinear evolution equation of the information entropy density changing in time and state variable space. Its mathematical form and physical meaning are similar to the evolution equation of the physical entropy: The time rate of change of information entropy density originates together from drift, diffusion and production. The concise statistical formula of information entropy production rate is similar to that of physical entropy also. Furthermore, we study the similarity and difference between physical entropy and information entropy and the possible unification of the two statistical entropies, and discuss the relationship among the principle of entropy increase, the principle of equilibrium maximum entropy and the principle of maximum information entropy as well as the connection between them and the entropy evolution equation.

Versatile single-molecule multi-color excitation and detection fluorescence setup for studying biomolecular dynamics

KAUST Repository

Sobhy, M. A.; Elshenawy, M. M.; Takahashi, Masateru; Whitman, B. H.; Walter, N. G.; Hamdan, S. M.

2011-01-01

Single-molecule fluorescence imaging is at the forefront of tools applied to study biomolecular dynamics both in vitro and in vivo. The ability of the single-molecule fluorescence microscope to conduct simultaneous multi-color excitation

Single molecule conductance

NARCIS (Netherlands)

Willems, R.

2008-01-01

This thesis represents an excursion into the world of molecular electronics, i.e. the field of research trying to use individual (organic) molecules as electronic components; in this work various experimental methods have been explored to connect individual molecules to metallic contacts and

Entropy, neutro-entropy and anti-entropy for neutrosophic information

OpenAIRE

Vasile Patrascu

2017-01-01

This article shows a deca-valued representation of neutrosophic information in which are defined the following features: truth, falsity, weak truth, weak falsity, ignorance, contradiction, saturation, neutrality, ambiguity and hesitation. Using these features, there are constructed computing formulas for entropy, neutro-entropy and anti-entropy.

Measurement of the conductance properties of single organic molecules using gold nanoparticles

Science.gov (United States)

Gordin, Yoav

In this work we describe the development and application of a new method for the electrical conductance measurement of single molecules. The issue of reliable theoretical modeling of molecular electronic transport is still very much in debate. The experimental methods used in the field are difficult to realize and interpret; most have very low yield, preventing proper statistical analysis and many have problems in the researchers' ability to characterize the system properly. We address this issue by using self assembly of gold nanoparticle-molecule-gold nanoparticle objects called dimers. This method allows fabrication of molecular junctions with greater ease; moreover it allows individual characterization of the various elements of the junction, removing much of the uncertainties that exist in this kind of measurements. We make use of home grown gold nanoparticles with a few tens of nanometer diameter to form the hybrid dimers. The dimers are large enough to connect between electrodes fabricated using electron beam lithography and to measure the electric properties of the molecule. We have invested significant effort in the characterization of the system, ensuring that the dimers are indeed bridged by the molecules, and that the chances that more than a single molecule exists in a dimer are negligibly small. We have made measurements on single gold nanoparticles, to characterize their properties separately from those of the molecule. These measurements have allowed us to observe single electron transistor (SET) behavior, resulting from the requirement that electrons charge the nanoparticle during transport. We have shown that the energy associated with this charging scales with nanoparticle size as expected. We have performed measurements on single organic molecules, showing that there is a very strong influence of molecular conjugation (the way electronic orbitals are spread along the molecular backbone) on its conductance. The molecules with broken conjugation

A general approach to break the concentration barrier in single-molecule imaging

KAUST Repository

Loveland, Anna B.; Habuchi, Satoshi; Walter, Johannes C.; van Oijen, Antoine M.

2012-01-01

Single-molecule fluorescence imaging is often incompatible with physiological protein concentrations, as fluorescence background overwhelms an individual molecule's signal. We solve this problem with a new imaging approach called PhADE (Photo

Single molecule SERS: Perspectives of analytical applications

Czech Academy of Sciences Publication Activity Database

Vlčková, B.; Pavel, I.; Sládková, M.; Šišková, K.; Šlouf, Miroslav

834-836, - (2007), s. 42-47 ISSN 0022-2860. [European Congress on Molecular Spectroscopy /28./. Istanbul, 03.09.2006-08.09.2006] R&D Projects: GA ČR GA203/04/0688 Institutional research plan: CEZ:AV0Z40500505 Keywords : surface-enhanced Raman scattering (SERS) * surface-enhanced resonance Raman (SERRS) * single molecule SERS Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.486, year: 2007

Statistical inference in single molecule measurements of protein adsorption

Science.gov (United States)

Armstrong, Megan J.; Tsitkov, Stanislav; Hess, Henry

2018-02-01

Significant effort has been invested into understanding the dynamics of protein adsorption on surfaces, in particular to predict protein behavior at the specialized surfaces of biomedical technologies like hydrogels, nanoparticles, and biosensors. Recently, the application of fluorescent single molecule imaging to this field has permitted the tracking of individual proteins and their stochastic contribution to the aggregate dynamics of adsorption. However, the interpretation of these results is complicated by (1) the finite time available to observe effectively infinite adsorption timescales and (2) the contribution of photobleaching kinetics to adsorption kinetics. Here, we perform a protein adsorption simulation to introduce specific survival analysis methods that overcome the first complication. Additionally, we collect single molecule residence time data from the adsorption of fibrinogen to glass and use survival analysis to distinguish photobleaching kinetics from protein adsorption kinetics.

An all-electric single-molecule motor.

Science.gov (United States)

Seldenthuis, Johannes S; Prins, Ferry; Thijssen, Joseph M; van der Zant, Herre S J

2010-11-23

Many types of molecular motors have been proposed and synthesized in recent years, displaying different kinds of motion, and fueled by different driving forces such as light, heat, or chemical reactions. We propose a new type of molecular motor based on electric field actuation and electric current detection of the rotational motion of a molecular dipole embedded in a three-terminal single-molecule device. The key aspect of this all-electronic design is the conjugated backbone of the molecule, which simultaneously provides the potential landscape of the rotor orientation and a real-time measure of that orientation through the modulation of the conductivity. Using quantum chemistry calculations, we show that this approach provides full control over the speed and continuity of motion, thereby combining electrical and mechanical control at the molecular level over a wide range of temperatures. Moreover, chemistry can be used to change all key parameters of the device, enabling a variety of new experiments on molecular motors.

Single-molecule conductance with nitrile and amino contacts with Ag or Cu electrodes

International Nuclear Information System (INIS)

Li, Dong-Fang; Mao, Jin-Chuan; Chen, De-Li; Chen, Fang; Ze-Wen, Hong; Zhou, Xiao-Yi; Wang, Ya-Hao; Zhou, Xiao-Shun; Niu, Zhen-Jiang; Maisonhaute, Emmanuel

2015-01-01

The single-molecule conductance of 1,4-dicyanobenzene (DCB), 1,4-benzenediamine (BDA) and 4,4'-biphenyldicarbonitrile (BPDC) with Ag and/or Cu electrodes is measured by electrochemical jump-to-contact STM-break junction. All single-molecule junctions present three sets of conductance values revealing different contact geometries. We observe that the single-molecule conductance of Ag-BDA-Ag junction is larger that of Ag-DCB-Ag junction, and DCB with Ag contacts are more conductive than that with Cu ones. This is related to a different electronic coupling between the molecules and the electrodes. Tunneling decay constants of 1.70 and 1.68 per phenyl group were found for Ag and Cu electrodes, respectively. The present study therefore shows that nitrile and amino groups can also be used as effective anchors for other metals than gold

Order and correlation contributions to the entropy of hydrophobic solvation

Energy Technology Data Exchange (ETDEWEB)

Liu, Maoyuan; Besford, Quinn Alexander; Mulvaney, Thomas; Gray-Weale, Angus, E-mail: gusgw@gusgw.net [School of Chemistry, The University of Melbourne, Victoria 3010 (Australia)

2015-03-21

The entropy of hydrophobic solvation has been explained as the result of ordered solvation structures, of hydrogen bonds, of the small size of the water molecule, of dispersion forces, and of solvent density fluctuations. We report a new approach to the calculation of the entropy of hydrophobic solvation, along with tests of and comparisons to several other methods. The methods are assessed in the light of the available thermodynamic and spectroscopic information on the effects of temperature on hydrophobic solvation. Five model hydrophobes in SPC/E water give benchmark solvation entropies via Widom’s test-particle insertion method, and other methods and models are tested against these particle-insertion results. Entropies associated with distributions of tetrahedral order, of electric field, and of solvent dipole orientations are examined. We find these contributions are small compared to the benchmark particle-insertion entropy. Competitive with or better than other theories in accuracy, but with no free parameters, is the new estimate of the entropy contributed by correlations between dipole moments. Dipole correlations account for most of the hydrophobic solvation entropy for all models studied and capture the distinctive temperature dependence seen in thermodynamic and spectroscopic experiments. Entropies based on pair and many-body correlations in number density approach the correct magnitudes but fail to describe temperature and size dependences, respectively. Hydrogen-bond definitions and free energies that best reproduce entropies from simulations are reported, but it is difficult to choose one hydrogen bond model that fits a variety of experiments. The use of information theory, scaled-particle theory, and related methods is discussed briefly. Our results provide a test of the Frank-Evans hypothesis that the negative solvation entropy is due to structured water near the solute, complement the spectroscopic detection of that solvation structure by

Maximum entropy decomposition of quadrupole mass spectra

International Nuclear Information System (INIS)

Toussaint, U. von; Dose, V.; Golan, A.

2004-01-01

We present an information-theoretic method called generalized maximum entropy (GME) for decomposing mass spectra of gas mixtures from noisy measurements. In this GME approach to the noisy, underdetermined inverse problem, the joint entropies of concentration, cracking, and noise probabilities are maximized subject to the measured data. This provides a robust estimation for the unknown cracking patterns and the concentrations of the contributing molecules. The method is applied to mass spectroscopic data of hydrocarbons, and the estimates are compared with those received from a Bayesian approach. We show that the GME method is efficient and is computationally fast

Electric-Field Control of Interfering Transport Pathways in a Single-Molecule Anthraquinone Transistor

Science.gov (United States)

Koole, Max; Thijssen, Jos M.; Valkenier, Hennie; Hummelen, Jan C.; Zant, Herre S. J. van der

2015-08-01

It is understood that molecular conjugation plays an important role in charge transport through single-molecule junctions. Here, we investigate electron transport through an anthraquinone based single-molecule three-terminal device. With the use of an electric-field induced by a gate electrode, the molecule is reduced resulting into a ten-fold increase in the off-resonant differential conductance. Theoretical calculations link the change in differential conductance to a reduction-induced change in conjugation, thereby lifting destructive interference of transport pathways.

Memory effects in single-molecule spectroscopy

International Nuclear Information System (INIS)

Schmitt, Daniel T.; Schulz, Michael; Reineker, Peter

2007-01-01

From the time series of LH2 optical single-molecule fluorescence excitation spectra of Rhodospirillum molischianum the memory function of the Mori-Zwanzig equation for the optical intensity is derived numerically. We show that the time dependence of the excited states is determined by at least three different non-Markovian stochastic processes with decay constants for the Mori-Zwanzig kernel on the order of 1-5min -1 . We suggest that this decay stems from the conformational motion of the protein scaffold of LH2

Absolute Configuration of Andrographolide and Its Proliferation of Osteoblast Cell Lines

Science.gov (United States)

Chantrapromma, S.; Boonnak, N.; Pitakpornpreecha, T.; Yordthong, T.; Chidan Kumar, C. S.; Fun, H. K.

2018-05-01

Andrographolide, C20H30O5, is a labdane diterpenoid which was isolated from the leave of Andrographis paniculata. Its crystal structure is determined by single crystal X-ray diffraction: monoclinic, sp. gr. P21, Z = 2. Absolute configuration is determined by the refinement of the Flack parameter to 0.21(19). In the crystal, molecules are linked by O-H···O hydrogen bonds and C-H···O interactions into two dimensional network parallel to the (001) plane. Its proliferation of osteoblast cell lines is reported.

Nanofluidic single-molecule sorting of DNA: a new concept in separation and analysis of biomolecules towards ultimate level performance

International Nuclear Information System (INIS)

Yamamoto, Takatoki; Fujii, Teruo

2010-01-01

Separation and separation-based analysis of biomolecules are fundamentally important techniques in the field of biotechnology. These techniques, however, depend on stochastic processes that intrinsically involve uncertainty, and thus it is not possible to achieve 100% separation accuracy. Theoretically, the ultimate resolution and sensitivity should be realized in a single-molecule system because of the deterministic nature of single-molecule manipulation. Here, we have proposed and experimentally demonstrated the concept of a 'single-molecule sorter' that detects and correctly identifies individual single molecules, realizing the ultimate level of resolution and sensitivity for any separation-based technology. The single-molecule sorter was created using a nanofluidic network consisting of a single inlet channel that branches off into multiple outlet channels. It includes two major functional elements, namely a single-molecule detection and identification element and a flow path switching element to accurately separate single molecules. With this system we have successfully demonstrated the world's first single-molecule sorting using DNA as a sample molecule. In the future, we hope to expand the application of such devices to comprehensive sorting of single-proteins from a single cell. We also believe that in addition to the single-molecule sorting method reported here, other types of single-molecule based processes will emerge and find use in a wide variety of applications.

Enzymatic production of single-molecule FISH and RNA capture probes.

Science.gov (United States)

Gaspar, Imre; Wippich, Frank; Ephrussi, Anne

2017-10-01

Arrays of singly labeled short oligonucleotides that hybridize to a specific target revolutionized RNA biology, enabling quantitative, single-molecule microscopy analysis and high-efficiency RNA/RNP capture. Here, we describe a simple and efficient method that allows flexible functionalization of inexpensive DNA oligonucleotides by different fluorescent dyes or biotin using terminal deoxynucleotidyl transferase and custom-made functional group conjugated dideoxy-UTP. We show that (i) all steps of the oligonucleotide labeling-including conjugation, enzymatic synthesis, and product purification-can be performed in a standard biology laboratory, (ii) the process yields >90%, often >95% labeled product with minimal carryover of impurities, and (iii) the oligonucleotides can be labeled with different dyes or biotin, allowing single-molecule FISH, RNA affinity purification, and Northern blot analysis to be performed. © 2017 Gaspar et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Single-molecule spectroscopy of amino acids and peptides by recognition tunnelling

Science.gov (United States)

Zhao, Yanan; Ashcroft, Brian; Zhang, Peiming; Liu, Hao; Sen, Suman; Song, Weisi; Im, Jongone; Gyarfas, Brett; Manna, Saikat; Biswas, Sovan; Borges, Chad; Lindsay, Stuart

2014-06-01

The human proteome has millions of protein variants due to alternative RNA splicing and post-translational modifications, and variants that are related to diseases are frequently present in minute concentrations. For DNA and RNA, low concentrations can be amplified using the polymerase chain reaction, but there is no such reaction for proteins. Therefore, the development of single-molecule protein sequencing is a critical step in the search for protein biomarkers. Here, we show that single amino acids can be identified by trapping the molecules between two electrodes that are coated with a layer of recognition molecules, then measuring the electron tunnelling current across the junction. A given molecule can bind in more than one way in the junction, and we therefore use a machine-learning algorithm to distinguish between the sets of electronic `fingerprints' associated with each binding motif. With this recognition tunnelling technique, we are able to identify D and L enantiomers, a methylated amino acid, isobaric isomers and short peptides. The results suggest that direct electronic sequencing of single proteins could be possible by sequentially measuring the products of processive exopeptidase digestion, or by using a molecular motor to pull proteins through a tunnel junction integrated with a nanopore.

Shedding Light on Protein Folding, Structural and Functional Dynamics by Single Molecule Studies

Directory of Open Access Journals (Sweden)

Krutika Bavishi

2014-11-01

Full Text Available The advent of advanced single molecule measurements unveiled a great wealth of dynamic information revolutionizing our understanding of protein dynamics and behavior in ways unattainable by conventional bulk assays. Equipped with the ability to record distribution of behaviors rather than the mean property of a population, single molecule measurements offer observation and quantification of the abundance, lifetime and function of multiple protein states. They also permit the direct observation of the transient and rarely populated intermediates in the energy landscape that are typically averaged out in non-synchronized ensemble measurements. Single molecule studies have thus provided novel insights about how the dynamic sampling of the free energy landscape dictates all aspects of protein behavior; from its folding to function. Here we will survey some of the state of the art contributions in deciphering mechanisms that underlie protein folding, structural and functional dynamics by single molecule fluorescence microscopy techniques. We will discuss a few selected examples highlighting the power of the emerging techniques and finally discuss the future improvements and directions.

Switching behavior of double-decker single molecule magnets on a metal surface

Energy Technology Data Exchange (ETDEWEB)

Fu, Yingshuang; Schwoebel, Joerg; Hoffmann, Germar; Brede, Jens; Wiesendanger, Roland [University of Hamburg, Hamburg (Germany); Dillulo, Andrew [Ohio University, Athens (United States); Klyatskaya, Svetlana [Karlsruhe Institute of Technology, Karlsruhe (Germany); Ruben, Mario [Karlsruhe Institute of Technology, Karlsruhe (Germany); Universite de Strasbourg, Strasbourg (France)

2011-07-01

Single molecule magnets (SMM) are most promising materials for spin based molecular electronics. Due to their large magnetic anisotropy stabilized by inside chemical bonds, SMM can potentially be used for information storage at the single molecule level. For applications, it is of importance to adsorb the SMM onto surfaces and to study their subsequent conformational, electronic and magnetic properties. We have investigated the adsorption behavior of Tb and Dy based double-decker SMM on an Ir(111) surface with low temperature scanning tunneling microscopy and spectroscopy. It is found that Tb double-decker molecules bind tightly to the Ir(111) surface. By resonantly injecting tunneling electrons into its LUMO or HOMO state, the Tb double-decker molecule can be switched from a four-lobed structure to an eight-lobed structure. After switching, energy positions of the HOMO and LUMO states both shift closer to the Fermi level. Dy double-decker molecules also exhibit the same switching properties on the Ir(111) surface. The switching behavior of the molecules is tentatively attributed to a conformational change of the double-decker molecular frame.

A general approach to break the concentration barrier in single-molecule imaging

KAUST Repository

Loveland, Anna B.

2012-09-09

Single-molecule fluorescence imaging is often incompatible with physiological protein concentrations, as fluorescence background overwhelms an individual molecule\\'s signal. We solve this problem with a new imaging approach called PhADE (PhotoActivation, Diffusion and Excitation). A protein of interest is fused to a photoactivatable protein (mKikGR) and introduced to its surface-immobilized substrate. After photoactivation of mKikGR near the surface, rapid diffusion of the unbound mKikGR fusion out of the detection volume eliminates background fluorescence, whereupon the bound molecules are imaged. We labeled the eukaryotic DNA replication protein flap endonuclease 1 with mKikGR and added it to replication-competent Xenopus laevis egg extracts. PhADE imaging of high concentrations of the fusion construct revealed its dynamics and micrometer-scale movements on individual, replicating DNA molecules. Because PhADE imaging is in principle compatible with any photoactivatable fluorophore, it should have broad applicability in revealing single-molecule dynamics and stoichiometry of macromolecular protein complexes at previously inaccessible fluorophore concentrations. © 2012 Nature America, Inc. All rights reserved.

Vastus lateralis single motor unit EMG at the same absolute torque production at different knee angles

NARCIS (Netherlands)

Altenburg, T.M.; de Haan, A.; Verdijk, P.W.; van Mechelen, W.; de Ruiter, C.J.

2009-01-01

Single motor unit electromyographic (EMG) activity of the knee extensors was investigated at different knee angles with subjects (n = 10) exerting the same absolute submaximal isometric torque at each angle. Measurements were made over a 20° range around the optimum angle for torque production

Vesicle Encapsulation Studies Reveal that Single Molecule Ribozyme Heterogeneities Are Intrinsic

Science.gov (United States)

Okumus, Burak; Wilson, Timothy J.; Lilley, David M. J.; Ha, Taekjip

2004-01-01

Single-molecule measurements have revealed that what were assumed to be identical molecules can differ significantly in their static and dynamic properties. One of the most striking examples is the hairpin ribozyme, which was shown to exhibit two to three orders of magnitude variation in folding kinetics between molecules. Although averaged behavior of single molecules matched the bulk solution data, it was not possible to exclude rigorously the possibility that the variations around the mean values arose from different ways of interacting with the surface environment. To test this, we minimized the molecules' interaction with the surface by encapsulating DNA or RNA molecules inside 100- to 200-nm diameter unilamellar vesicles, following the procedures described by Haran and coworkers. Vesicles were immobilized on a supported lipid bilayer via biotin-streptavidin linkages. We observed no direct binding of DNA or RNA on the supported bilayer even at concentrations exceeding 100 nM, indicating that these molecules do not bind stably on the membrane. Since the vesicle diameter is smaller than the resolution of optical microscopy, the lateral mobility of the molecules is severely constrained, allowing long observation periods. We used fluorescence correlation spectroscopy, nuclease digestion, and external buffer exchange to show that the molecules were indeed encapsulated within the vesicles. When contained within vesicles, the natural form of the hairpin ribozyme exhibited 50-fold variation in both folding and unfolding rates in 0.5 mM Mg2+, which is identical to what was observed from the molecules tethered directly on the surface. This strongly indicates that the observed heterogeneity in dynamic properties does not arise as an artifact of surface attachment, but is intrinsic to the nature of the molecules. PMID:15454471

Towards the coupling of single photons from dye molecules to a photonic waveguide

Science.gov (United States)

Polisseni, Claudio; Kho, Kiang Wei; Major, Kyle; Grandi, Samuele; Boisser, Sebastien; Hwang, Jaesuk; Clark, Alex; Hinds, Edward

Single photons are very attractive for quantum information processing given their long coherence time and their ability to carry information in many degrees of freedom. A current challenge is the efficient generation of single photons in a photonic chip in order to scale up the complexity of quantum operations. We have proposed that a dibenzoterrylene (DBT) molecule inside an anthracene (AC) crystal could couple lifetime-limited indistinguishable single photons into a photonic waveguide if deposited in its vicinity. In this talk I describe the recent progress towards the realization of this proposal. A new method has been developed for evaporating AC and DBT to produce crystals that are wide and thin. The crystals are typically several microns across and have remarkably uniform thickness, which we control between 20 and 150 nm. The crystal growth is carried out in a glove bag in order to exclude oxygen, which improves the photostability of the DBT molecules by orders of magnitude. We image the fluorescence of single DBT molecules using confocal microscopy and analyse the polarization of this light to determine the alignment of the molecules. I will report on our efforts to control the alignement of the molecules by aligning the host matrix with the substrate.

Dye molecules as single-photon sources and large optical nonlinearities on a chip

International Nuclear Information System (INIS)

Hwang, J; Hinds, E A

2011-01-01

We point out that individual organic dye molecules, deposited close to optical waveguides on a photonic chip, can act as single-photon sources. A thin silicon nitride strip waveguide is expected to collect 28% of the photons from a single dibenzoterrylene molecule. These molecules can also provide large, localized optical nonlinearities, which are enough to discriminate between one photon or two through a differential phase shift of 2 0 per photon. This new atom-photon interface may be used as a resource for processing quantum information.

Optical Microcavity: Sensing down to Single Molecules and Atoms

Directory of Open Access Journals (Sweden)

Shu-Yu Su

2011-02-01

Full Text Available This review article discusses fundamentals of dielectric, low-loss, optical micro-resonator sensing, including figures of merit and a variety of microcavity designs, and future perspectives in microcavity-based optical sensing. Resonance frequency and quality (Q factor are altered as a means of detecting a small system perturbation, resulting in realization of optical sensing of a small amount of sample materials, down to even single molecules. Sensitivity, Q factor, minimum detectable index change, noises (in sensor system components and microcavity system including environments, microcavity size, and mode volume are essential parameters to be considered for optical sensing applications. Whispering gallery mode, photonic crystal, and slot-type microcavities typically provide compact, high-quality optical resonance modes for optical sensing applications. Surface Bloch modes induced on photonic crystals are shown to be a promising candidate thanks to large field overlap with a sample and ultra-high-Q resonances. Quantum optics effects based on microcavity quantum electrodynamics (QED would provide novel single-photo-level detection of even single atoms and molecules via detection of doublet vacuum Rabi splitting peaks in strong coupling.

Revealing time bunching effect in single-molecule enzyme conformational dynamics.

Science.gov (United States)

Lu, H Peter

2011-04-21

In this perspective, we focus our discussion on how the single-molecule spectroscopy and statistical analysis are able to reveal enzyme hidden properties, taking the study of T4 lysozyme as an example. Protein conformational fluctuations and dynamics play a crucial role in biomolecular functions, such as in enzymatic reactions. Single-molecule spectroscopy is a powerful approach to analyze protein conformational dynamics under physiological conditions, providing dynamic perspectives on a molecular-level understanding of protein structure-function mechanisms. Using single-molecule fluorescence spectroscopy, we have probed T4 lysozyme conformational motions under the hydrolysis reaction of a polysaccharide of E. coli B cell walls by monitoring the fluorescence resonant energy transfer (FRET) between a donor-acceptor probe pair tethered to T4 lysozyme domains involving open-close hinge-bending motions. Based on the single-molecule spectroscopic results, molecular dynamics simulation, a random walk model analysis, and a novel 2D statistical correlation analysis, we have revealed a time bunching effect in protein conformational motion dynamics that is critical to enzymatic functions. Bunching effect implies that conformational motion times tend to bunch in a finite and narrow time window. We show that convoluted multiple Poisson rate processes give rise to the bunching effect in the enzymatic reaction dynamics. Evidently, the bunching effect is likely common in protein conformational dynamics involving in conformation-gated protein functions. In this perspective, we will also discuss a new approach of 2D regional correlation analysis capable of analyzing fluctuation dynamics of complex multiple correlated and anti-correlated fluctuations under a non-correlated noise background. Using this new method, we are able to map out any defined segments along the fluctuation trajectories and determine whether they are correlated, anti-correlated, or non-correlated; after which, a

Flexible single molecule simulation of reaction-diffusion processes

International Nuclear Information System (INIS)

Hellander, Stefan; Loetstedt, Per

2011-01-01

An algorithm is developed for simulation of the motion and reactions of single molecules at a microscopic level. The molecules diffuse in a solvent and react with each other or a polymer and molecules can dissociate. Such simulations are of interest e.g. in molecular biology. The algorithm is similar to the Green's function reaction dynamics (GFRD) algorithm by van Zon and ten Wolde where longer time steps can be taken by computing the probability density functions (PDFs) and then sample from the distribution functions. Our computation of the PDFs is much less complicated than GFRD and more flexible. The solution of the partial differential equation for the PDF is split into two steps to simplify the calculations. The sampling is without splitting error in two of the coordinate directions for a pair of molecules and a molecule-polymer interaction and is approximate in the third direction. The PDF is obtained either from an analytical solution or a numerical discretization. The errors due to the operator splitting, the partitioning of the system, and the numerical approximations are analyzed. The method is applied to three different systems involving up to four reactions. Comparisons with other mesoscopic and macroscopic models show excellent agreement.

Experimental techniques for single cell and single molecule biomechanics

International Nuclear Information System (INIS)

Lim, C.T.; Zhou, E.H.; Li, A.; Vedula, S.R.K.; Fu, H.X.

2006-01-01

Stresses and strains that act on the human body can arise either from external physical forces or internal physiological environmental conditions. These biophysical interactions can occur not only at the musculoskeletal but also cellular and molecular levels and can determine the health and function of the human body. Here, we seek to investigate the structure-property-function relationship of cells and biomolecules so as to understand their important physiological functions as well as establish possible connections to human diseases. With the recent advancements in cell and molecular biology, biophysics and nanotechnology, several innovative and state-of-the-art experimental techniques and equipment have been developed to probe the structural and mechanical properties of biostructures from the micro- down to picoscale. Some of these experimental techniques include the optical or laser trap method, micropipette aspiration, step-pressure technique, atomic force microscopy and molecular force spectroscopy. In this article, we will review the basic principles and usage of these techniques to conduct single cell and single molecule biomechanics research

Fabrication and interfacing of nanochannel devices for single-molecule studies

International Nuclear Information System (INIS)

Hoang, H T; Berenschot, J W; De Boer, M J; Tas, N R; Haneveld, J; Elwenspoek, M C; Segers-Nolten, I M

2009-01-01

Nanochannel devices have been fabricated using standard micromachining techniques such as optical lithography, deposition and etching. 1D nanochannels with thin glass capping and through-wafer inlet/outlet ports were constructed. 2D nanochannels have been made transparent by oxidation of polysilicon channel wall for optical detection and these fragile channels were successfully connected to macro inlet ports. The interfacing from the macro world to the nanochannels was especially designed for optical observation of filling liquid inside nanochannels using an inverted microscope. Toward single-molecule studies, individual quantum dots were visualized in 150 nm height 1D nanochannels. The potential of 2D nanochannels for single-molecule studies was shown from a filling experiment with a fluorescent dye solution

Lanthanide single molecule magnets

CERN Document Server

Tang, Jinkui

2015-01-01

This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs, and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures – an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and...

3D single-molecule super-resolution microscopy with a tilted light sheet.

Science.gov (United States)

Gustavsson, Anna-Karin; Petrov, Petar N; Lee, Maurice Y; Shechtman, Yoav; Moerner, W E

2018-01-09

Tilted light sheet microscopy with 3D point spread functions (TILT3D) combines a novel, tilted light sheet illumination strategy with long axial range point spread functions (PSFs) for low-background, 3D super-localization of single molecules as well as 3D super-resolution imaging in thick cells. Because the axial positions of the single emitters are encoded in the shape of each single-molecule image rather than in the position or thickness of the light sheet, the light sheet need not be extremely thin. TILT3D is built upon a standard inverted microscope and has minimal custom parts. The result is simple and flexible 3D super-resolution imaging with tens of nm localization precision throughout thick mammalian cells. We validate TILT3D for 3D super-resolution imaging in mammalian cells by imaging mitochondria and the full nuclear lamina using the double-helix PSF for single-molecule detection and the recently developed tetrapod PSFs for fiducial bead tracking and live axial drift correction.

Control of Single Molecule Fluorescence Dynamics by Stimulated Emission Depletion

OpenAIRE

Marsh, R. J.; Osborne, M. A.; Bain, A. J.

2003-01-01

The feasibility of manipulating the single molecule absorption-emission cycle using picosecond stimulated emission depletion (STED) is investigated using a stochastic computer simulation. In the simulation the molecule is subjected to repeated excitation and depletion events using time delayed pairs of excitation (PUMP) and depletion (DUMP) pulses derived from a high repetition rate pulsed laser system. The model is used to demonstrate that a significant and even substantial reduction in the ...

Multivariate multiscale entropy of financial markets

Science.gov (United States)

Lu, Yunfan; Wang, Jun

2017-11-01

In current process of quantifying the dynamical properties of the complex phenomena in financial market system, the multivariate financial time series are widely concerned. In this work, considering the shortcomings and limitations of univariate multiscale entropy in analyzing the multivariate time series, the multivariate multiscale sample entropy (MMSE), which can evaluate the complexity in multiple data channels over different timescales, is applied to quantify the complexity of financial markets. Its effectiveness and advantages have been detected with numerical simulations with two well-known synthetic noise signals. For the first time, the complexity of four generated trivariate return series for each stock trading hour in China stock markets is quantified thanks to the interdisciplinary application of this method. We find that the complexity of trivariate return series in each hour show a significant decreasing trend with the stock trading time progressing. Further, the shuffled multivariate return series and the absolute multivariate return series are also analyzed. As another new attempt, quantifying the complexity of global stock markets (Asia, Europe and America) is carried out by analyzing the multivariate returns from them. Finally we utilize the multivariate multiscale entropy to assess the relative complexity of normalized multivariate return volatility series with different degrees.

Topological entropy of autonomous flows

Energy Technology Data Exchange (ETDEWEB)

Badii, R. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

1997-06-01

When studying fluid dynamics, especially in a turbulent regime, it is crucial to estimate the number of active degrees of freedom or of localized structures in the system. The topological entropy quantifies the exponential growth of the number of `distinct` orbits in a dynamical system as a function of their length, in the infinite spatial resolution limit. Here, I illustrate a novel method for its evaluation, which extends beyond maps and is applicable to any system, including autonomous flows: these are characterized by lack of a definite absolute time scale for the orbit lengths. (author) 8 refs.

Estimating the melting point, entropy of fusion, and enthalpy of ...

Science.gov (United States)

The entropies of fusion, enthalies of fusion, and melting points of organic compounds can be estimated through three models developed using the SPARC (SPARC Performs Automated Reasoning in Chemistry) platform. The entropy of fusion is modeled through a combination of interaction terms and physical descriptors. The enthalpy of fusion is modeled as a function of the entropy of fusion, boiling point, and fexibility of the molecule. The melting point model is the enthlapy of fusion divided by the entropy of fusion. These models were developed in part to improve SPARC's vapor pressure and solubility models. These models have been tested on 904 unique compounds. The entropy model has a RMS of 12.5 J mol-1K-1. The enthalpy model has a RMS of 4.87 kJ mol-1. The melting point model has a RMS of 54.4°C. Published in the journal, SAR and QSAR in Environmental Research

Single-molecule denaturation mapping of DNA in nanofluidic channels

DEFF Research Database (Denmark)

Reisner, Walter; Larsen, Niels Bent; Silahtaroglu, Asli

2010-01-01

Here we explore the potential power of denaturation mapping as a single-molecule technique. By partially denaturing YOYO (R)-1-labeled DNA in nanofluidic channels with a combination of formamide and local heating, we obtain a sequence-dependent "barcode" corresponding to a series of local dips...... and peaks in the intensity trace along the extended molecule. We demonstrate that this structure arises from the physics of local denaturation: statistical mechanical calculations of sequence-dependent melting probability can predict the barcode to be observed experimentally for a given sequence...

Spatial and temporal superresolution concepts to study plasma membrane organization by single molecule fluorescence techniques

International Nuclear Information System (INIS)

Ruprecht, V.

2010-01-01

Fluorescence microscopy techniques are currently among the most important experimental tools to study cellular processes. Ultra-sensitive detection devices nowadays allow for measuring even individual farnesylacetate labeled target molecules with nanometer spatial accuracy and millisecond time resolution. The emergence of single molecule fluorescence techniques especially contributed to the field of membrane biology and provided basic knowledge on structural and dynamic features of the cellular plasma membrane. However, we are still confronted with a rather fragmentary understanding of the complex architecture and functional interrelations of membrane constituents. In this thesis new concepts in one- and dual-color single molecule fluorescence techniques are presented that allow for addressing organization principles and interaction dynamics in the live cell plasma membrane. Two complementary experimental strategies are described which differ in their detection principle: single molecule fluorescence imaging and fluorescence correlation spectroscopy. The presented methods are discussed in terms of their implementation, accuracy, quantitative and statistical data analysis, as well as live cell applications. State-of-the-art dual color single molecule imaging is introduced as the most direct experimental approach to study interaction dynamics between differently labeled target molecules. New analytical estimates for robust data analysis are presented that facilitate quantitative recording and identification of co localizations in dual color single molecule images. A novel dual color illumination scheme is further described that profoundly extends the current range and sensitivity of conventional dual color single molecule experiments. The method enables working at high surface densities of fluorescent molecules - a feature typically incommensurable with single molecule imaging - and is especially suited for the detection of rare interactions by tracking co localized

Applied thermodynamics of the real gas with respect to the thermodynamic zeros of the entropy and internal energy

International Nuclear Information System (INIS)

Elsner, Albrecht

2012-01-01

Gibbs's work on the thermodynamic properties of substances presented a complete thermodynamic theory. The formulations of the entropy S and internal energy U as extensive quantities allow the zeros of the real gas to be given: S=0 at absolute zero (Nernst, Planck) and U=0 at the critical point. Consequently, every thermodynamic function is unique and absolutely specified. Interdependences among quantities such as temperature, vapor pressure, chemical potential, volume, entropy, internal energy, and heat capacity are likewise unique and numerically well defined. This is shown for the saturated fluid, water, in the region between absolute zero and the critical point. As a consequence of the calculation of the chemical potential, it follows that the free particle flow in an inhomogeneous system is essentially governed by the difference in chemical potential, and not through the difference in pressure, this effect being of importance for meteorology and oceanography.

Kondo effect in single-molecule magnet transistors

Science.gov (United States)

Gonzalez, Gabriel; Leuenberger, Michael; Mucciolo, Eduardo

2009-03-01

We present a careful and thorough microscopic derivation of the anisotropic Kondo Hamiltonian for single-molecule magnet (SMM) transistors. When the molecule is strongly coupled to metallic leads, we show that by applying a transverse magnetic field it is possible to topologically induce or quench the Kondo effect in the conductance of a SMM with either an integer or a half-integer spin S>1/2. This topological Kondo effect is due to the Berry-phase interference between multiple quantum tunneling paths of the spin. We calculate the renormalized Berry-phase oscillations of the two Kondo peaks as a function of a transverse magnetic field by means of the poor man's scaling approach. We illustrate our findings with the SMM Ni4, which we propose as a possible candidate for the experimental observation of the conductance oscillations.

Electron-vibron coupling effects on electron transport via a single-molecule magnet

NARCIS (Netherlands)

McCaskey, A.; Yamamoto, Y.; Warnock, M.; Burzuri, E.; Van der Zant, H.S.J.; Park, K.

2015-01-01

We investigate how the electron-vibron coupling influences electron transport via an anisotropic magnetic molecule, such as a single-molecule magnet (SMM) Fe4, by using a model Hamiltonian with parameter values obtained from density-functional theory (DFT). The magnetic anisotropy parameters,

Lanthanide single molecule magnets

Energy Technology Data Exchange (ETDEWEB)

Tang, Jinkui; Zhang, Peng [Chinese Academy of Sciences, Changchun (China). Changchun Inst. of Applied Chemistry

2015-10-01

This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures - an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and explore new directions.

Giant Magnetoresistance in Carbon Nanotubes with Single-Molecule Magnets TbPc2.

Science.gov (United States)

Krainov, Igor V; Klier, Janina; Dmitriev, Alexander P; Klyatskaya, Svetlana; Ruben, Mario; Wernsdorfer, Wolfgang; Gornyi, Igor V

2017-07-25

We present experimental results and a theoretical model for the gate-controlled spin-valve effect in carbon nanotubes with side-attached single-molecule magnets TbPc 2 (Terbium(III) bis-phthalocyanine). These structures show a giant magnetoresistance up to 1000% in experiments on single-wall nanotubes that are tunnel-coupled to the leads. The proposed theoretical model combines the spin-dependent Fano effect with Coulomb blockade and predicts a spin-spin interaction between the TbPc 2 molecules, mediated by conducting electrons via the charging effect. This gate-tuned interaction is responsible for the stable magnetic ordering of the inner spins of the molecules in the absence of magnetic field. In the case of antiferromagnetic arrangement, electrons with either spin experience the scattering by the molecules, which results in blocking the linear transport. In strong magnetic fields, the Zeeman energy exceeds the effective antiferromagnetic coupling and one species of electrons is not scattered by molecules, which leads to a much lower total resistance at the resonant values of gate voltage, and hence to a supramolecular spin-valve effect.

Elastin-like Polypeptide Linkers for Single-Molecule Force Spectroscopy.

Science.gov (United States)

Ott, Wolfgang; Jobst, Markus A; Bauer, Magnus S; Durner, Ellis; Milles, Lukas F; Nash, Michael A; Gaub, Hermann E

2017-06-27

Single-molecule force spectroscopy (SMFS) is by now well established as a standard technique in biophysics and mechanobiology. In recent years, the technique has benefitted greatly from new approaches to bioconjugation of proteins to surfaces. Indeed, optimized immobilization strategies for biomolecules and refined purification schemes are being steadily adapted and improved, which in turn has enhanced data quality. In many previously reported SMFS studies, poly(ethylene glycol) (PEG) was used to anchor molecules of interest to surfaces and/or cantilever tips. The limitation, however, is that PEG exhibits a well-known trans-trans-gauche to all-trans transition, which results in marked deviation from standard polymer elasticity models such as the worm-like chain, particularly at elevated forces. As a result, the assignment of unfolding events to protein domains based on their corresponding amino acid chain lengths is significantly obscured. Here, we provide a solution to this problem by implementing unstructured elastin-like polypeptides as linkers to replace PEG. We investigate the suitability of tailored elastin-like polypeptides linkers and perform direct comparisons to PEG, focusing on attributes that are critical for single-molecule force experiments such as linker length, monodispersity, and bioorthogonal conjugation tags. Our results demonstrate that by avoiding the ambiguous elastic response of mixed PEG/peptide systems and instead building the molecular mechanical systems with only a single bond type with uniform elastic properties, we improve data quality and facilitate data analysis and interpretation in force spectroscopy experiments. The use of all-peptide linkers allows alternative approaches for precisely defining elastic properties of proteins linked to surfaces.

Single-molecule detection of dihydroazulene photo-thermal reaction using break junction technique

Science.gov (United States)

Huang, Cancan; Jevric, Martyn; Borges, Anders; Olsen, Stine T.; Hamill, Joseph M.; Zheng, Jue-Ting; Yang, Yang; Rudnev, Alexander; Baghernejad, Masoud; Broekmann, Peter; Petersen, Anne Ugleholdt; Wandlowski, Thomas; Mikkelsen, Kurt V.; Solomon, Gemma C.; Brøndsted Nielsen, Mogens; Hong, Wenjing

2017-05-01

Charge transport by tunnelling is one of the most ubiquitous elementary processes in nature. Small structural changes in a molecular junction can lead to significant difference in the single-molecule electronic properties, offering a tremendous opportunity to examine a reaction on the single-molecule scale by monitoring the conductance changes. Here, we explore the potential of the single-molecule break junction technique in the detection of photo-thermal reaction processes of a photochromic dihydroazulene/vinylheptafulvene system. Statistical analysis of the break junction experiments provides a quantitative approach for probing the reaction kinetics and reversibility, including the occurrence of isomerization during the reaction. The product ratios observed when switching the system in the junction does not follow those observed in solution studies (both experiment and theory), suggesting that the junction environment was perturbing the process significantly. This study opens the possibility of using nano-structured environments like molecular junctions to tailor product ratios in chemical reactions.

Investigation of polyelectrolyte desorption by single molecule force spectroscopy

International Nuclear Information System (INIS)

Friedsam, C; Seitz, M; Gaub, H E

2004-01-01

Single molecule force spectroscopy has evolved into a powerful method for the investigation of intra- and intermolecular interactions at the level of individual molecules. Many examples, including the investigation of the dynamic properties of complex biological systems as well as the properties of covalent bonds or intermolecular transitions within individual polymers, are reported in the literature. The technique has recently been extended to the systematic investigation of desorption processes of individual polyelectrolyte molecules adsorbed on generic surfaces. The stable covalent attachment of polyelectrolyte molecules to the AFM-tip provides the possibility of performing long-term measurements with the same set of molecules and therefore allows the in situ observation of the impact of environmental changes on the adsorption behaviour of individual molecules. Different types of interactions, e.g. electrostatic or hydrophobic interactions, that determine the adsorption process could be identified and characterized. The experiments provided valuable details that help to understand the nature and the properties of non-covalent interactions, which is helpful with regard to biological systems as well as for technical applications. Apart from this, desorption experiments can be utilized to characterize the properties of surfaces or polymer coatings. Therefore they represent a versatile tool that can be further developed in terms of various aspects

Single-cell multiple gene expression analysis based on single-molecule-detection microarray assay for multi-DNA determination

Energy Technology Data Exchange (ETDEWEB)

Li, Lu [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China); Wang, Xianwei [School of Life Sciences, Shandong University, Jinan 250100 (China); Zhang, Xiaoli [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China); Wang, Jinxing [School of Life Sciences, Shandong University, Jinan 250100 (China); Jin, Wenrui, E-mail: jwr@sdu.edu.cn [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China)

2015-01-07

Highlights: • A single-molecule-detection (SMD) microarray for 10 samples is fabricated. • The based-SMD microarray assay (SMA) can determine 8 DNAs for each sample. • The limit of detection of SMA is as low as 1.3 × 10{sup −16} mol L{sup −1}. • The SMA can be applied in single-cell multiple gene expression analysis. - Abstract: We report a novel ultra-sensitive and high-selective single-molecule-detection microarray assay (SMA) for multiple DNA determination. In the SMA, a capture DNA (DNAc) microarray consisting of 10 subarrays with 9 spots for each subarray is fabricated on a silanized glass coverslip as the substrate. On the subarrays, the spot-to-spot spacing is 500 μm and each spot has a diameter of ∼300 μm. The sequence of the DNAcs on the 9 spots of a subarray is different, to determine 8 types of target DNAs (DNAts). Thus, 8 types of DNAts are captured to their complementary DNAcs at 8 spots of a subarray, respectively, and then labeled with quantum dots (QDs) attached to 8 types of detection DNAs (DNAds) with different sequences. The ninth spot is used to detect the blank value. In order to determine the same 8 types of DNAts in 10 samples, the 10 DNAc-modified subarrays on the microarray are identical. Fluorescence single-molecule images of the QD-labeled DNAts on each spot of the subarray are acquired using a home-made single-molecule microarray reader. The amounts of the DNAts are quantified by counting the bright dots from the QDs. For a microarray, 8 types of DNAts in 10 samples can be quantified in parallel. The limit of detection of the SMA for DNA determination is as low as 1.3 × 10{sup −16} mol L{sup −1}. The SMA for multi-DNA determination can also be applied in single-cell multiple gene expression analysis through quantification of complementary DNAs (cDNAs) corresponding to multiple messenger RNAs (mRNAs) in single cells. To do so, total RNA in single cells is extracted and reversely transcribed into their cDNAs. Three

Single molecule dynamics at a mechanically controllable break junction in solution at room temperature.

Science.gov (United States)

Konishi, Tatsuya; Kiguchi, Manabu; Takase, Mai; Nagasawa, Fumika; Nabika, Hideki; Ikeda, Katsuyoshi; Uosaki, Kohei; Ueno, Kosei; Misawa, Hiroaki; Murakoshi, Kei

2013-01-23

The in situ observation of geometrical and electronic structural dynamics of a single molecule junction is critically important in order to further progress in molecular electronics. Observations of single molecular junctions are difficult, however, because of sensitivity limits. Here, we report surface-enhanced Raman scattering (SERS) of a single 4,4'-bipyridine molecule under conditions of in situ current flow in a nanogap, by using nano-fabricated, mechanically controllable break junction (MCBJ) electrodes. When adsorbed at room temperature on metal nanoelectrodes in solution to form a single molecule junction, statistical analysis showed that nontotally symmetric b(1) and b(2) modes of 4,4'-bipyridine were strongly enhanced relative to observations of the same modes in solid or aqueous solutions. Significant changes in SERS intensity, energy (wavenumber), and selectivity of Raman vibrational bands that are coincident with current fluctuations provide information on distinct states of electronic and geometrical structure of the single molecule junction, even under large thermal fluctuations occurring at room temperature. We observed the dynamics of 4,4'-bipyridine motion between vertical and tilting configurations in the Au nanogap via b(1) and b(2) mode switching. A slight increase in the tilting angle of the molecule was also observed by noting the increase in the energies of Raman modes and the decrease in conductance of the molecular junction.

Characterizing single-molecule FRET dynamics with probability distribution analysis.

Science.gov (United States)

Santoso, Yusdi; Torella, Joseph P; Kapanidis, Achillefs N

2010-07-12

Probability distribution analysis (PDA) is a recently developed statistical tool for predicting the shapes of single-molecule fluorescence resonance energy transfer (smFRET) histograms, which allows the identification of single or multiple static molecular species within a single histogram. We used a generalized PDA method to predict the shapes of FRET histograms for molecules interconverting dynamically between multiple states. This method is tested on a series of model systems, including both static DNA fragments and dynamic DNA hairpins. By fitting the shape of this expected distribution to experimental data, the timescale of hairpin conformational fluctuations can be recovered, in good agreement with earlier published results obtained using different techniques. This method is also applied to studying the conformational fluctuations in the unliganded Klenow fragment (KF) of Escherichia coli DNA polymerase I, which allows both confirmation of the consistency of a simple, two-state kinetic model with the observed smFRET distribution of unliganded KF and extraction of a millisecond fluctuation timescale, in good agreement with rates reported elsewhere. We expect this method to be useful in extracting rates from processes exhibiting dynamic FRET, and in hypothesis-testing models of conformational dynamics against experimental data.

On the Possibility of Calculating Entropy, Free Energy, and Enthalpy of Vitreous Substances

Directory of Open Access Journals (Sweden)

Sergei V. Nemilov

2018-03-01

Full Text Available A critical analysis for the arguments in support of, and against, the traditional approach to thermodynamics of vitreous state is provided. In this approach one presumes that there is a continuous variation of the entropy in the glass-liquid transition temperature range, or a “continuous entropy approach” towards 0 K which produces a positive value of the entropy at T → 0 K. I find that arguments given against this traditional approach use a different understanding of the thermodynamics of glass transition on cooling a liquid, because it suggests a discontinuity or “entropy loss approach” in the variation of entropy in the glass-liquid transition range. That is based on: (1 an unjustifiable use of the classical Boltzmann statistics for interpreting the value of entropy at absolute zero; (2 the rejection of thermodynamic analysis of systems with broken ergodicity, even though the possibility of analogous analysis was proposed already by Gibbs; (3 the possibility of a finite change in entropy of a system without absorption or release of heat; and, (4 describing the thermodynamic properties of glasses in the framework of functions, instead of functionals. The last one is necessary because for glasses the entropy and enthalpy are not functions of the state, but functionals, as defined by Gibbs’ in his classification.

Effect of the environment on the electrical conductance of the single benzene-1,4-diamine molecule junction

Directory of Open Access Journals (Sweden)

Shigeto Nakashima

2011-11-01

Full Text Available We investigated the effect of the environment on the electrical conductance of a single benzene-1,4-diamine (BDA molecule bridging Au electrodes, using the scanning tunneling microscope (STM. The conductance of the single BDA molecule junction decreased upon a change in the environment from tetraglyme, to mesitylene, to water, and finally to N2 gas, while the spread in the conductance value increased. The order of the conductance values of the single BDA molecule junction was explained by the strength of the interaction between the solvent molecules and the Au electrodes. The order of the spread in the conductance values was explained by the diversity in the coverage of the BDA molecule at metal electrodes and atomic and molecular motion of the single-molecule junction.

Bright photoactivatable fluorophores for single-molecule imaging.

Science.gov (United States)

Grimm, Jonathan B; English, Brian P; Choi, Heejun; Muthusamy, Anand K; Mehl, Brian P; Dong, Peng; Brown, Timothy A; Lippincott-Schwartz, Jennifer; Liu, Zhe; Lionnet, Timothée; Lavis, Luke D

2016-12-01

Small-molecule fluorophores are important tools for advanced imaging experiments. We previously reported a general method to improve small, cell-permeable fluorophores which resulted in the azetidine-containing 'Janelia Fluor' (JF) dyes. Here, we refine and extend the utility of these dyes by synthesizing photoactivatable derivatives that are compatible with live-cell labeling strategies. Once activated, these derived compounds retain the superior brightness and photostability of the JF dyes, enabling improved single-particle tracking and facile localization microscopy experiments.

Binding and Translocation of Termination Factor Rho Studied at the Single-Molecule Level

Science.gov (United States)

Koslover, Daniel J.; Fazal, Furqan M.; Mooney, Rachel A.; Landick, Robert; Block, Steven M.

2012-01-01

Rho termination factor is an essential hexameric helicase responsible for terminating 20–50% of all mRNA synthesis in E. coli. We used single- molecule force spectroscopy to investigate Rho-RNA binding interactions at the Rho- utilization (rut) site of the ? tR1 terminator. Our results are consistent with Rho complexes adopting two states, one that binds 57 ±2 nucleotides of RNA across all six of the Rho primary binding sites, and another that binds 85 ±2 nucleotides at the six primary sites plus a single secondary site situated at the center of the hexamer. The single-molecule data serve to establish that Rho translocates 5′-to-3′ towards RNA polymerase (RNAP) by a tethered-tracking mechanism, looping out the intervening RNA between the rut site and RNAP. These findings lead to a general model for Rho binding and translocation, and establish a novel experimental approach that should facilitate additional single- molecule studies of RNA-binding proteins. PMID:22885804

A versatile optical microscope for time-dependent single-molecule and single-particle spectroscopy

Science.gov (United States)

Li, Hao; Yang, Haw

2018-03-01

This work reports the design and implementation of a multi-function optical microscope for time-dependent spectroscopy on single molecules and single nanoparticles. It integrates the now-routine single-object measurements into one standalone platform so that no reconfiguration is needed when switching between different types of sample or spectroscopy modes. The illumination modes include evanescent field through total internal reflection, dark-field illumination, and epi-excitation onto a diffraction-limited spot suitable for confocal detection. The detection modes include spectrally resolved line imaging, wide-field imaging with dual-color capability, and two-color single-element photon-counting detection. The switch between different spectroscopy and data acquisition modes is fully automated and executed through computer programming. The capability of this microscope is demonstrated through selected proof-of-principle experiments.

A versatile optical microscope for time-dependent single-molecule and single-particle spectroscopy.

Science.gov (United States)

Li, Hao; Yang, Haw

2018-03-28

This work reports the design and implementation of a multi-function optical microscope for time-dependent spectroscopy on single molecules and single nanoparticles. It integrates the now-routine single-object measurements into one standalone platform so that no reconfiguration is needed when switching between different types of sample or spectroscopy modes. The illumination modes include evanescent field through total internal reflection, dark-field illumination, and epi-excitation onto a diffraction-limited spot suitable for confocal detection. The detection modes include spectrally resolved line imaging, wide-field imaging with dual-color capability, and two-color single-element photon-counting detection. The switch between different spectroscopy and data acquisition modes is fully automated and executed through computer programming. The capability of this microscope is demonstrated through selected proof-of-principle experiments.

Drift correction for single-molecule imaging by molecular constraint field, a distance minimum metric

International Nuclear Information System (INIS)

Han, Renmin; Wang, Liansan; Xu, Fan; Zhang, Yongdeng; Zhang, Mingshu; Liu, Zhiyong; Ren, Fei; Zhang, Fa

2015-01-01

The recent developments of far-field optical microscopy (single molecule imaging techniques) have overcome the diffraction barrier of light and improve image resolution by a factor of ten compared with conventional light microscopy. These techniques utilize the stochastic switching of probe molecules to overcome the diffraction limit and determine the precise localizations of molecules, which often requires a long image acquisition time. However, long acquisition times increase the risk of sample drift. In the case of high resolution microscopy, sample drift would decrease the image resolution. In this paper, we propose a novel metric based on the distance between molecules to solve the drift correction. The proposed metric directly uses the position information of molecules to estimate the frame drift. We also designed an algorithm to implement the metric for the general application of drift correction. There are two advantages of our method: First, because our method does not require space binning of positions of molecules but directly operates on the positions, it is more natural for single molecule imaging techniques. Second, our method can estimate drift with a small number of positions in each temporal bin, which may extend its potential application. The effectiveness of our method has been demonstrated by both simulated data and experiments on single molecular images

Single-Molecule Fluorescence Studies of Membrane Transporters Using Total Internal Reflection Microscopy.

Science.gov (United States)

Goudsmits, Joris M H; van Oijen, Antoine M; Slotboom, Dirk J

2017-01-01

Cells are delineated by a lipid bilayer that physically separates the inside from the outer environment. Most polar, charged, or large molecules require proteins to reduce the energetic barrier for passage across the membrane and to achieve transport rates that are relevant for life. Here, we describe techniques to visualize the functioning of membrane transport proteins with fluorescent probes at the single-molecule level. First, we explain how to produce membrane-reconstituted transporters with fluorescent labels. Next, we detail the construction of a microfluidic flow cell to image immobilized proteoliposomes on a total internal reflection fluorescence microscope. We conclude by describing the methods that are needed to analyze fluorescence movies and obtain useful single-molecule data. © 2017 Elsevier Inc. All rights reserved.

Smart SERS Hot Spots: Single Molecules Can Be Positioned in a Plasmonic Nanojunction Using Host-Guest Chemistry.

Science.gov (United States)

Kim, Nam Hoon; Hwang, Wooseup; Baek, Kangkyun; Rohman, Md Rumum; Kim, Jeehong; Kim, Hyun Woo; Mun, Jungho; Lee, So Young; Yun, Gyeongwon; Murray, James; Ha, Ji Won; Rho, Junsuk; Moskovits, Martin; Kim, Kimoon

2018-04-04

Single-molecule surface-enhanced Raman spectroscopy (SERS) offers new opportunities for exploring the complex chemical and biological processes that cannot be easily probed using ensemble techniques. However, the ability to place the single molecule of interest reliably within a hot spot, to enable its analysis at the single-molecule level, remains challenging. Here we describe a novel strategy for locating and securing a single target analyte in a SERS hot spot at a plasmonic nanojunction. The "smart" hot spot was generated by employing a thiol-functionalized cucurbit[6]uril (CB[6]) as a molecular spacer linking a silver nanoparticle to a metal substrate. This approach also permits one to study molecules chemically reluctant to enter the hot spot, by conjugating them to a moiety, such as spermine, that has a high affinity for CB[6]. The hot spot can accommodate at most a few, and often only a single, analyte molecule. Bianalyte experiments revealed that one can reproducibly treat the SERS substrate such that 96% of the hot spots contain a single analyte molecule. Furthermore, by utilizing a series of molecules each consisting of spermine bound to perylene bisimide, a bright SERS molecule, with polymethylene linkers of varying lengths, the SERS intensity as a function of distance from the center of the hot spot could be measured. The SERS enhancement was found to decrease as 1 over the square of the distance from the center of the hot spot, and the single-molecule SERS cross sections were found to increase with AgNP diameter.

Imaging Live Cells at the Nanometer-Scale with Single-Molecule Microscopy: Obstacles and Achievements in Experiment Optimization for Microbiology

Science.gov (United States)

Haas, Beth L.; Matson, Jyl S.; DiRita, Victor J.; Biteen, Julie S.

2015-01-01

Single-molecule fluorescence microscopy enables biological investigations inside living cells to achieve millisecond- and nanometer-scale resolution. Although single-molecule-based methods are becoming increasingly accessible to non-experts, optimizing new single-molecule experiments can be challenging, in particular when super-resolution imaging and tracking are applied to live cells. In this review, we summarize common obstacles to live-cell single-molecule microscopy and describe the methods we have developed and applied to overcome these challenges in live bacteria. We examine the choice of fluorophore and labeling scheme, approaches to achieving single-molecule levels of fluorescence, considerations for maintaining cell viability, and strategies for detecting single-molecule signals in the presence of noise and sample drift. We also discuss methods for analyzing single-molecule trajectories and the challenges presented by the finite size of a bacterial cell and the curvature of the bacterial membrane. PMID:25123183

Influence of quantum dot labels on single molecule movement in the plasma membrane

DEFF Research Database (Denmark)

Clausen, Mathias P.; Lagerholm, B. Christoffer

2011-01-01

Single particle tracking results are very dependent on the probe that is used. In this study we have investigated the influence that functionalized quantum dots (QDs) have on the recorded movement in single molecule tracking experiments of plasma membrane species in live cells. Potential issues...... for simultaneous investigations of different plasma membrane species in order to discriminate the effect of the label from differences in movement of the target molecules....

Single Molecule Scanning of DNA Radiation Oxidative Damage, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — This proposal will develop an assay to map genomic DNA, at the single molecule level and in a nanodevice, for oxidative DNA damage arising from radiation exposure;...

Rationale for single molecule detection by means of Raman spectroscopy

International Nuclear Information System (INIS)

Gaponenko, S.V.; Guzatov, D.V.

2009-01-01

A consistent quantum electrodynamical description is proposed of Raman scattering of light by a molecule in a medium with a modified photon density of states. Enhanced local density of states near a metal nanobody is shown to increase a scattering rate by several orders of magnitude, thus providing a rationale for experimental detection of single molecules by means of Raman spectroscopy. For an ellipsoidal particle 10 14 -fold enhancement of the Raman scattering cross-section is obtained. (authors)

Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

Science.gov (United States)

Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

2014-09-01

Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy

Future Directions for Transuranic Single Molecule Magnets

Directory of Open Access Journals (Sweden)

Nicola Magnani

2018-02-01

Full Text Available Single Molecule Magnets (SMMs based on transition metals and rare earths have been the object of considerable attention for the past 25 years. These systems exhibit slow relaxation of the magnetization, arising from a sizeable anisotropy barrier, and magnetic hysteresis of purely molecular origin below a given blocking temperature. Despite initial predictions that SMMs based on 5f-block elements could outperform most others, the results obtained so far have not met expectations. Exploiting the versatile chemistry of actinides and their favorable intrinsic magnetic properties proved, indeed, to be more difficult than assumed. However, the large majority of studies reported so far have been dedicated to uranium molecules, thus leaving the largest part of the 5f-block practically unexplored. Here, we present a short review of the progress achieved up to now and discuss some options for a possible way forward.

Entropy Measurement for Biometric Verification Systems.

Science.gov (United States)

Lim, Meng-Hui; Yuen, Pong C

2016-05-01

Biometric verification systems are designed to accept multiple similar biometric measurements per user due to inherent intrauser variations in the biometric data. This is important to preserve reasonable acceptance rate of genuine queries and the overall feasibility of the recognition system. However, such acceptance of multiple similar measurements decreases the imposter's difficulty of obtaining a system-acceptable measurement, thus resulting in a degraded security level. This deteriorated security needs to be measurable to provide truthful security assurance to the users. Entropy is a standard measure of security. However, the entropy formula is applicable only when there is a single acceptable possibility. In this paper, we develop an entropy-measuring model for biometric systems that accepts multiple similar measurements per user. Based on the idea of guessing entropy, the proposed model quantifies biometric system security in terms of adversarial guessing effort for two practical attacks. Excellent agreement between analytic and experimental simulation-based measurement results on a synthetic and a benchmark face dataset justify the correctness of our model and thus the feasibility of the proposed entropy-measuring approach.

Sub-Poissonian statistics of quantum jumps in single molecule or atomic ion

International Nuclear Information System (INIS)

Osad'ko, I.S.; Gus'kov, D.N.

2007-01-01

A theory for statistics of quantum jumps in single molecule or ion driven by continues wave laser field is developed. These quantum jumps can relate to nonradiative singlet-triplet transitions in a molecule or to on → off jumps in a single ion with shelving processes. Distribution function w N (T) of quantum jumps in time interval T is found. Computer simulation of quantum jumps is realized. Statistical treatment of simulated jumps reveals sub-Poissonian statistics of quantum jumps. The theoretical distribution function w N (T) fits well the distribution of jumps found from simulated data. Experimental data on quantum jumps found in experiments with single Hg + ion are described by the function w N (T) well

madSTORM: a superresolution technique for large-scale multiplexing at single-molecule accuracy

Science.gov (United States)

Yi, Jason; Manna, Asit; Barr, Valarie A.; Hong, Jennifer; Neuman, Keir C.; Samelson, Lawrence E.

2016-01-01

Investigation of heterogeneous cellular structures using single-molecule localization microscopy has been limited by poorly defined localization accuracy and inadequate multiplexing capacity. Using fluorescent nanodiamonds as fiducial markers, we define and achieve localization precision required for single-molecule accuracy in dSTORM images. Coupled with this advance, our new multiplexing strategy, madSTORM, allows accurate targeting of multiple molecules using sequential binding and elution of fluorescent antibodies. madSTORM is used on an activated T-cell to localize 25 epitopes, 14 of which are on components of the same multimolecular T-cell receptor complex. We obtain an average localization precision of 2.6 nm, alignment error of 2.0 nm, and molecules within structures. Probing the molecular topology of complex signaling cascades and other heterogeneous networks is feasible with madSTORM. PMID:27708141

Detection of gas molecules on single Mn adatom adsorbed graphyne: a DFT-D study

Science.gov (United States)

Lu, Zhansheng; Lv, Peng; Ma, Dongwei; Yang, Xinwei; Li, Shuo; Yang, Zongxian

2018-02-01

As one of the prominent applications in intelligent systems, gas sensing technology has attracted great interest in both industry and academia. In the current study, the pristine graphyne (GY) without and with a single Mn atom is investigated to detect the gas molecules (CO, CH4, CO2, NH3, NO and O2). The pristine GY is promising to detect O2 molecules because of its chemical adsorption on GY with large electron transfer. The great stability of the Mn/GY is found, and the Mn atom prefers to anchor at the alkyne ring as a single atom. Upon single Mn atom anchoring, the sensitivity and selectivity of GY based gas sensors is significantly improved for various molecules, except CH4. The recovery time of the Mn/GY after detecting the gas molecules may help to appraise the detection efficiency for the Mn/GY. The current study will help to understand the mechanism of detecting the gas molecules, and extend the potentially fascinating applications of GY-based materials.

Quantum entropy and special relativity.

Science.gov (United States)

Peres, Asher; Scudo, Petra F; Terno, Daniel R

2002-06-10

We consider a single free spin- 1 / 2 particle. The reduced density matrix for its spin is not covariant under Lorentz transformations. The spin entropy is not a relativistic scalar and has no invariant meaning.

Configurational entropy change of netropsin and distamycin upon DNA minor-groove binding.

Science.gov (United States)

Dolenc, Jozica; Baron, Riccardo; Oostenbrink, Chris; Koller, Joze; van Gunsteren, Wilfred F

2006-08-15

Binding of a small molecule to a macromolecular target reduces its conformational freedom, resulting in a negative entropy change that opposes the binding. The goal of this study is to estimate the configurational entropy change of two minor-groove-binding ligands, netropsin and distamycin, upon binding to the DNA duplex d(CGCGAAAAACGCG).d(CGCGTTTTTCGCG). Configurational entropy upper bounds based on 10-ns molecular dynamics simulations of netropsin and distamycin in solution and in complex with DNA in solution were estimated using the covariance matrix of atom-positional fluctuations. The results suggest that netropsin and distamycin lose a significant amount of configurational entropy upon binding to the DNA minor groove. The estimated changes in configurational entropy for netropsin and distamycin are -127 J K(-1) mol(-1) and -104 J K(-1) mol(-1), respectively. Estimates of the configurational entropy contributions of parts of the ligands are presented, showing that the loss of configurational entropy is comparatively more pronounced for the flexible tails than for the relatively rigid central body.

Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

Science.gov (United States)

Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

2016-03-01

Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

Injection molded nanofluidic chips: Fabrication method and functional tests using single-molecule DNA experiments

DEFF Research Database (Denmark)

Utko, Pawel; Persson, Karl Fredrik; Kristensen, Anders

2011-01-01

We demonstrate that fabrication of nanofluidic systems can be greatly simplified by injection molding of polymers. We functionally test our devices by single-molecule DNA experiments in nanochannels.......We demonstrate that fabrication of nanofluidic systems can be greatly simplified by injection molding of polymers. We functionally test our devices by single-molecule DNA experiments in nanochannels....

Measurement and understanding of single-molecule break junction rectification caused by asymmetric contacts

International Nuclear Information System (INIS)

Wang, Kun; Zhou, Jianfeng; Hamill, Joseph M.; Xu, Bingqian

2014-01-01

The contact effects of single-molecule break junctions on rectification behaviors were experimentally explored by a systematic control of anchoring groups of 1,4-disubstituted benzene molecular junctions. Single-molecule conductance and I-V characteristic measurements reveal a strong correlation between rectifying effects and the asymmetry in contacts. Analysis using energy band models and I-V calculations suggested that the rectification behavior is mainly caused by asymmetric coupling strengths at the two contact interfaces. Fitting of the rectification ratio by a modified Simmons model we developed suggests asymmetry in potential drop across the asymmetric anchoring groups as the mechanism of rectifying I-V behavior. This study provides direct experimental evidence and sheds light on the mechanisms of rectification behavior induced simply by contact asymmetry, which serves as an aid to interpret future single-molecule electronic behavior involved with asymmetric contact conformation

Berry-phase blockade in single-molecule magnets

OpenAIRE

Gonzalez, Gabriel; Leuenberger, Michael N.

2006-01-01

We formulate the problem of electron transport through a single-molecule magnet (SMM) in the Coulomb blockade regime taking into account topological interference effects for the tunneling of the large spin of a SMM. The interference originates from spin Berry phases associated with different tunneling paths. We show that in the case of incoherent spin states it is essential to place the SMM between oppositely spin-polarized source and drain leads in order to detect the spin tunneling in the s...

Thermal deposition of intact tetrairon(III) single-molecule magnets in high-vacuum conditions.

Science.gov (United States)

Margheriti, Ludovica; Mannini, Matteo; Sorace, Lorenzo; Gorini, Lapo; Gatteschi, Dante; Caneschi, Andrea; Chiappe, Daniele; Moroni, Riccardo; de Mongeot, Francesco Buatier; Cornia, Andrea; Piras, Federica M; Magnani, Agnese; Sessoli, Roberta

2009-06-01

A tetrairon(III) single-molecule magnet is deposited using a thermal evaporation technique in high vacuum. The chemical integrity is demonstrated by time-of-flight secondary ion mass spectrometry on a film deposited on Al foil, while superconducting quantum interference device magnetometry and alternating current susceptometry of a film deposited on a kapton substrate show magnetic properties identical to the pristine powder. High-frequency electron paramagnetic resonance spectra confirm the characteristic behavior for a system with S = 5 and a large Ising-type magnetic anisotropy. All these results indicate that the molecules are not damaged during the deposition procedure keeping intact the single-molecule magnet behavior.

Compact quantum dots for single-molecule imaging.

Science.gov (United States)

Smith, Andrew M; Nie, Shuming

2012-10-09

Single-molecule imaging is an important tool for understanding the mechanisms of biomolecular function and for visualizing the spatial and temporal heterogeneity of molecular behaviors that underlie cellular biology (1-4). To image an individual molecule of interest, it is typically conjugated to a fluorescent tag (dye, protein, bead, or quantum dot) and observed with epifluorescence or total internal reflection fluorescence (TIRF) microscopy. While dyes and fluorescent proteins have been the mainstay of fluorescence imaging for decades, their fluorescence is unstable under high photon fluxes necessary to observe individual molecules, yielding only a few seconds of observation before complete loss of signal. Latex beads and dye-labeled beads provide improved signal stability but at the expense of drastically larger hydrodynamic size, which can deleteriously alter the diffusion and behavior of the molecule under study. Quantum dots (QDs) offer a balance between these two problematic regimes. These nanoparticles are composed of semiconductor materials and can be engineered with a hydrodynamically compact size with exceptional resistance to photodegradation (5). Thus in recent years QDs have been instrumental in enabling long-term observation of complex macromolecular behavior on the single molecule level. However these particles have still been found to exhibit impaired diffusion in crowded molecular environments such as the cellular cytoplasm and the neuronal synaptic cleft, where their sizes are still too large (4,6,7). Recently we have engineered the cores and surface coatings of QDs for minimized hydrodynamic size, while balancing offsets to colloidal stability, photostability, brightness, and nonspecific binding that have hindered the utility of compact QDs in the past (8,9). The goal of this article is to demonstrate the synthesis, modification, and characterization of these optimized nanocrystals, composed of an alloyed HgxCd1-xSe core coated with an

Single molecule insights on conformational selection and induced fit mechanism

DEFF Research Database (Denmark)

Hatzakis, Nikos

2014-01-01

. To describe the molecular basis of this behavior, two main mechanisms have been advanced: 'induced fit' and 'conformational selection'. Our understanding of these models relies primarily on NMR, computational studies and kinetic measurements. These techniques report the average behavior of a large ensemble...... of unsynchronized molecules, often masking intrinsic dynamic behavior of proteins and biologically significant transient intermediates. Single molecule measurements are emerging as a powerful tool for characterizing protein function. They offer the direct observation and quantification of the activity, abundance...

Fabrication of birefringent nanocylinders for single-molecule force and torque measurement

Science.gov (United States)

Li, Ping-Chun; Chang, Jen-Chien; La Porta, Arthur; Yu, Edward T.

2014-06-01

Optically anisotropic subwavelength scale dielectric particles have been shown to enable studies of the mechanical properties of bio-molecules via optical trapping and manipulation. However, techniques emphasized to date for fabrication of such particles generally suffer from limited uniformity and control over particle dimensions, or low throughput and high cost. Here, an approach for rapid, low-cost, fabrication of large quantities of birefringent quartz nanocylinders with dimensions optimized for optical torque wrench experiments is described. For a typical process, 108 or more quartz cylinders with diameters of 500 nm and heights of 800 nm, with uniformity of ±5% in each dimension, can be fabricated over ˜10 cm2 areas, for binding to a single bio-molecule, and harvested for use in optical trapping experiments. Use of these structures to measure extensional and torsional dynamics of single DNA molecules is demonstrated with measured forces and torques shown to be in very good agreement with previously reported results.

Fabrication of birefringent nanocylinders for single-molecule force and torque measurement

International Nuclear Information System (INIS)

Li, Ping-Chun; T Yu, Edward; Chang, Jen-Chien; La Porta, Arthur

2014-01-01

Optically anisotropic subwavelength scale dielectric particles have been shown to enable studies of the mechanical properties of bio-molecules via optical trapping and manipulation. However, techniques emphasized to date for fabrication of such particles generally suffer from limited uniformity and control over particle dimensions, or low throughput and high cost. Here, an approach for rapid, low-cost, fabrication of large quantities of birefringent quartz nanocylinders with dimensions optimized for optical torque wrench experiments is described. For a typical process, 10 8 or more quartz cylinders with diameters of 500 nm and heights of 800 nm, with uniformity of ±5% in each dimension, can be fabricated over ∼10 cm 2 areas, for binding to a single bio-molecule, and harvested for use in optical trapping experiments. Use of these structures to measure extensional and torsional dynamics of single DNA molecules is demonstrated with measured forces and torques shown to be in very good agreement with previously reported results. (papers)

Single-Molecule Fluorescence Microscopy Reveals Local Diffusion Coefficients in the Pore Network of an Individual Catalyst Particle

NARCIS (Netherlands)

Hendriks, Frank|info:eu-repo/dai/nl/412642697; Meirer, Florian; Kubarev, Alexey V.; Ristanovic, Zoran|info:eu-repo/dai/nl/328233005; Roeffaers, Maarten B J; Vogt, Eelco T. C.|info:eu-repo/dai/nl/073717398; Bruijnincx, Pieter C. A.|info:eu-repo/dai/nl/33799529X; Weckhuysen, Bert M.|info:eu-repo/dai/nl/285484397

2017-01-01

We used single-molecule fluorescence microscopy to study self-diffusion of a feedstock-like probe molecule with nanometer accuracy in the macropores of a micrometer-sized, real-life fluid catalytic cracking (FCC) particle. Movies of single fluorescent molecules allowed their movement through the

Method for preparation and readout of polyatomic molecules in single quantum states

Science.gov (United States)

Patterson, David

2018-03-01

Polyatomic molecular ions contain many desirable attributes of a useful quantum system, including rich internal degrees of freedom and highly controllable coupling to the environment. To date, the vast majority of state-specific experimental work on molecular ions has concentrated on diatomic species. The ability to prepare and read out polyatomic molecules in single quantum states would enable diverse experimental avenues not available with diatomics, including new applications in precision measurement, sensitive chemical and chiral analysis at the single-molecule level, and precise studies of Hz-level molecular tunneling dynamics. While cooling the motional state of a polyatomic ion via sympathetic cooling with a laser-cooled atomic ion is straightforward, coupling this motional state to the internal state of the molecule has proven challenging. Here we propose a method for readout and projective measurement of the internal state of a trapped polyatomic ion. The method exploits the rich manifold of technically accessible rotational states in the molecule to realize robust state preparation and readout with far less stringent engineering than quantum logic methods recently demonstrated on diatomic molecules. The method can be applied to any reasonably small (≲10 atoms) polyatomic ion with an anisotropic polarizability.

Molecular interpretation of Trouton's and Hildebrand's rules for the entropy of vaporization of a liquid

International Nuclear Information System (INIS)

Green, James A.; Irudayam, Sheeba Jem; Henchman, Richard H.

2011-01-01

Research highlights: → A method to calculate a liquid's entropy of vaporization is proposed. → The entropy of vaporisation depends on force magnitudes from computer simulation. → Calculated values agree with experiment, Trouton's rule and Hildebrand's rule. → Free volumes decrease for larger molecules or those with stronger interactions. - Abstract: The entropy of vaporization at a liquid's boiling point is well approximated by Trouton's rule and even more accurately by Hildebrand's rule. A cell method is used here to calculate the entropy of vaporization for a range of liquids by subtracting the entropy of the gas from that of the liquid. The liquid's entropy is calculated from the force magnitudes measured in a molecular dynamics simulation based on the harmonic approximation. The change in rotational entropy is not accounted for except in the case of liquid water. The predicted entropies of vaporization agree well with experiment and Trouton's and Hildebrand's rules for most liquids and for water except other liquids with hydrogen bonds. This supports the idea that molecular rotation is close to ideal at a liquid's boiling point if hydrogen bonds are absent; if they are present, then the rotational entropy gain must be included. The method provides a molecular interpretation of those rules by providing an equation in terms of a molecule's free volume in a liquid which depends on the force magnitudes. Free volumes at each liquid's boiling point are calculated to be ∼1 A 3 for liquids lacking hydrogen bonds, lower at ∼0.3 A 3 for those with hydrogen bonds, and they decrease weakly with increasing molecular size.

Magnetization reversal in single molecule magnets

Science.gov (United States)

Bokacheva, Louisa

2002-09-01

I have studied the magnetization reversal in single molecule magnets (SMMs). SMMs are Van der Waals crystals, consisting of identical molecules containing transition metal ions, with high spin and large uniaxial magnetic anisotropy. They can be considered as ensembles of identical, iso-oriented nanomagnets. At high temperature, these materials behave as superparamagnets and their magnetization reversal occurs by thermal activation. At low temperature they become blocked, and their magnetic relaxation occurs via thermally assisted tunneling or pure quantum tunneling through the anisotropy barrier. We have conducted detailed experimental studies of the magnetization reversal in SMM material Mn12-acetate (Mn12) with S = 10. Low temperature measurements were conducted using micro-Hall effect magnetometry. We performed hysteresis and relaxation studies as a function of temperature, transverse field, and magnetization state of the sample. We identified magnetic sublevels that dominate the tunneling at a given field, temperature and magnetization. We observed a crossover between thermally assisted and pure quantum tunneling. The form of this crossover depends on the magnitude and direction of the applied field. This crossover is abrupt (first-order) and occurs in a narrow temperature interval (tunneling mechanisms in Mn12.

Asymptotics of information entropies of some Toda-like potentials

International Nuclear Information System (INIS)

Dehesa, J. S.; Martinez-Finkelshtein, A.; Sorokin, V. N.

2003-01-01

The spreading of the quantum probability density for the highly-excited states of a single-particle system with an exponential-type potential on the positive semiaxis is quantitatively determined in both position and momentum spaces by means of the Boltzmann-Shannon information entropy. This problem boils down to the calculation of the asymptotics of the entropy-like integrals of the modified Bessel function of the second kind (also called the Mcdonald function or Basset function). The dependence of the two physical entropies on the large quantum number n is given in detail. It is shown that the semiclassical (WKB) position-space entropy grows slower than the corresponding quantity of not only the harmonic oscillator but also the single-particle systems with any power-type potential of the form V(x)=x 2k , x(set-membership sign)R and k(set-membership sign)N. The momentum-space entropy, calculated with a method based on the properties of the Mcdonald function, is rigorously found to have a behavior of the form -ln ln n, in strong contrast with the corresponding quantity of other one-dimensional systems known up to now (power-type potentials, infinite well)

Dipolar molecules inside C-70: an electric field-driven room-temperature single-molecule switch

Czech Academy of Sciences Publication Activity Database

Foroutan-Nejad, C.; Andrushchenko, Valery; Straka, Michal

2016-01-01

Roč. 18, č. 48 (2016), s. 32673-32677 ISSN 1463-9076 R&D Projects: GA ČR(CZ) GA14-03564S Institutional support: RVO:61388963 Keywords : room-temperature single-molecule switch * electric field * endohedral fullerene * density functional calculations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.123, year: 2016 http://pubs.rsc.org/en/content/articlepdf/2016/cp/c6cp06986j

A wireless centrifuge force microscope (CFM) enables multiplexed single-molecule experiments in a commercial centrifuge.

Science.gov (United States)

Hoang, Tony; Patel, Dhruv S; Halvorsen, Ken

2016-08-01

The centrifuge force microscope (CFM) was recently introduced as a platform for massively parallel single-molecule manipulation and analysis. Here we developed a low-cost and self-contained CFM module that works directly within a commercial centrifuge, greatly improving accessibility and ease of use. Our instrument incorporates research grade video microscopy, a power source, a computer, and wireless transmission capability to simultaneously monitor many individually tethered microspheres. We validated the instrument by performing single-molecule force shearing of short DNA duplexes. For a 7 bp duplex, we observed over 1000 dissociation events due to force dependent shearing from 2 pN to 12 pN with dissociation times in the range of 10-100 s. We extended the measurement to a 10 bp duplex, applying a 12 pN force clamp and directly observing single-molecule dissociation over an 85 min experiment. Our new CFM module facilitates simple and inexpensive experiments that dramatically improve access to single-molecule analysis.

Impact of Anchoring Groups on Ballistic Transport: Single Molecule vs Monolayer Junctions

Science.gov (United States)

2015-01-01

Tuning the transport properties of molecular junctions by chemically modifying the molecular structure is one of the key challenges for advancing the field of molecular electronics. In the present contribution, we investigate current–voltage characteristics of differently linked metal–molecule–metal systems that comprise either a single molecule or a molecular assembly. This is achieved by employing density functional theory in conjunction with a Green’s function approach. We show that the conductance of a molecular system with a specific anchoring group is fundamentally different depending on whether a single molecule or a continuous monolayer forms the junction. This is a consequence of collective electrostatic effects that arise from dipolar elements contained in the monolayer and from interfacial charge rearrangements. As a consequence of these collective effects, the “ideal” choice for an anchoring group is clearly different for monolayer and single molecule devices. A particularly striking effect is observed for pyridine-docked systems. These are subject to Fermi-level pinning at high molecular packing densities, causing an abrupt increase of the junction current already at small voltages. PMID:26401191

Entropy Coherent and Entropy Convex Measures of Risk

NARCIS (Netherlands)

Laeven, R.J.A.; Stadje, M.A.

2011-01-01

We introduce two subclasses of convex measures of risk, referred to as entropy coherent and entropy convex measures of risk. We prove that convex, entropy convex and entropy coherent measures of risk emerge as certainty equivalents under variational, homothetic and multiple priors preferences,

Single-molecule three-color FRET with both negligible spectral overlap and long observation time.

Directory of Open Access Journals (Sweden)

Sanghwa Lee

Full Text Available Full understanding of complex biological interactions frequently requires multi-color detection capability in doing single-molecule fluorescence resonance energy transfer (FRET experiments. Existing single-molecule three-color FRET techniques, however, suffer from severe photobleaching of Alexa 488, or its alternative dyes, and have been limitedly used for kinetics studies. In this work, we developed a single-molecule three-color FRET technique based on the Cy3-Cy5-Cy7 dye trio, thus providing enhanced observation time and improved data quality. Because the absorption spectra of three fluorophores are well separated, real-time monitoring of three FRET efficiencies was possible by incorporating the alternating laser excitation (ALEX technique both in confocal microscopy and in total-internal-reflection fluorescence (TIRF microscopy.

Hyperspectral interferometry for single-shot absolute measurement of 3-D shape and displacement fields

Directory of Open Access Journals (Sweden)

Ruiz P. D.

2010-06-01

Full Text Available We propose a method that we call Hyperspectral Interferometry (HSI to resolve the 2π phase unwrapping problem in the analysis of interferograms recorded with a narrow-band light source. By using a broad-band light source and hyperspectral imaging system, a set of interferograms at different wavenumbers are recorded simultaneously on a high resolution image sensor. These are then assembled to form a three-dimensional intensity distribution. By Fourier transformation along the wavenumber axis, an absolute optical path difference is obtained for each pixel independently of the other pixels in the field of view. As a result, interferograms with spatially distinct regions are analysed as easily as continuous ones. The approach is illustrated with a HSI system to measure 3-D profiles of optically smooth or rough surfaces. Compared to existing profilometers able to measure absolute path differences, the single shot nature of the approach provides greater immunity from environmental disturbance.

Single-molecule experiments in biological physics: methods and applications.

Science.gov (United States)

Ritort, F

2006-08-16

I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

Single-molecule experiments in biological physics: methods and applications

International Nuclear Information System (INIS)

Ritort, F

2006-01-01

I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives. (topical review)

Single Molecule Spectroscopy in Chemistry, Physics and Biology Nobel Symposium

CERN Document Server

Gräslund, Astrid; Widengren, Jerker

2010-01-01

Written by the leading experts in the field, this book describes the development and current state-of-the-art in single molecule spectroscopy. The application of this technique, which started 1989, in physics, chemistry and biosciences is displayed.

Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy

Science.gov (United States)

Neuman, Keir C.; Nagy, Attila

2012-01-01

Single-molecule force spectroscopy has emerged as a powerful tool to investigate the forces and motions associated with biological molecules and enzymatic activity. The most common force spectroscopy techniques are optical tweezers, magnetic tweezers and atomic force microscopy. These techniques are described and illustrated with examples highlighting current capabilities and limitations. PMID:18511917

Entropy coherent and entropy convex measures of risk

NARCIS (Netherlands)

Laeven, Roger; Stadje, M.A.

2010-01-01

We introduce entropy coherent and entropy convex measures of risk and prove a collection of axiomatic characterization and duality results. We show in particular that entropy coherent and entropy convex measures of risk emerge as negative certainty equivalents in (the regular and a generalized

Scaling from single molecule to macroscopic adhesion at polymer/metal interfaces.

Science.gov (United States)

Utzig, Thomas; Raman, Sangeetha; Valtiner, Markus

2015-03-10

Understanding the evolution of macroscopic adhesion based on fundamental molecular interactions is crucial to designing strong and smart polymer/metal interfaces that play an important role in many industrial and biomedical applications. Here we show how macroscopic adhesion can be predicted on the basis of single molecular interactions. In particular, we carry out dynamic single molecule-force spectroscopy (SM-AFM) in the framework of Bell-Evans' theory to gain information about the energy barrier between the bound and unbound states of an amine/gold junction. Furthermore, we use Jarzynski's equality to obtain the equilibrium ground-state energy difference of the amine/gold bond from these nonequilibrium force measurements. In addition, we perform surface forces apparatus (SFA) experiments to measure macroscopic adhesion forces at contacts where approximately 10(7) amine/gold bonds are formed simultaneously. The SFA approach provides an amine/gold interaction energy (normalized by the number of interacting molecules) of (36 ± 1)k(B)T, which is in excellent agreement with the interaction free energy of (35 ± 3)k(B)T calculated using Jarzynski's equality and single-molecule AFM experiments. Our results validate Jarzynski's equality for the field of polymer/metal interactions by measuring both sides of the equation. Furthermore, the comparison of SFA and AFM shows how macroscopic interaction energies can be predicted on the basis of single molecular interactions, providing a new strategy to potentially predict adhesive properties of novel glues or coatings as well as bio- and wet adhesion.

A stochastic model for magnetic dynamics in single-molecule magnets

Energy Technology Data Exchange (ETDEWEB)

López-Ruiz, R., E-mail: rlruiz@ifi.unicamp.br [Instituto de Física Gleb Wataghin - Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Almeida, P.T. [Instituto de Física Gleb Wataghin - Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Vaz, M.G.F. [Instituto de Química, Universidade Federal Fluminense, 24020-150 Niterói (RJ) (Brazil); Novak, M.A. [Instituto de Física - Universidade Federal do Rio de Janeiro, 21941-972 Rio de Janeiro (RJ) (Brazil); Béron, F.; Pirota, K.R. [Instituto de Física Gleb Wataghin - Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil)

2016-04-01

Hysteresis and magnetic relaxation curves were performed on double well potential systems with quantum tunneling possibility via stochastic simulations. Simulation results are compared with experimental ones using the Mn{sub 12} single-molecule magnet, allowing us to introduce time dependence in the model. Despite being a simple simulation model, it adequately reproduces the phenomenology of a thermally activated quantum tunneling and can be extended to other systems with different parameters. Assuming competition between the reversal modes, thermal (over) and tunneling (across) the anisotropy barrier, a separation of classical and quantum contributions to relaxation time can be obtained. - Highlights: • Single-molecule magnets are modeled using a simple stochastic approach. • Simulation reproduces thermally-activated tunnelling magnetization reversal features. • The time is introduced in hysteresis and relaxation simulations. • We can separate the quantum and classical contributions to decay time.

Configurational entropy of charged AdS black holes

Directory of Open Access Journals (Sweden)

Chong Oh Lee

2017-09-01

Full Text Available When we consider charged AdS black holes in higher dimensional spacetime and a molecule number density along coexistence curves is numerically extended to higher dimensional cases. It is found that a number density difference of a small and large black holes decrease as a total dimension grows up. In particular, we find that a configurational entropy is a concave function of a reduced temperature and reaches a maximum value at a critical (second-order phase transition point. Furthermore, the bigger a total dimension becomes, the more concave function in a configurational entropy while the more convex function in a reduced pressure.

Single molecule magnet behaviour in robust dysprosium-biradical complexes.

Science.gov (United States)

Bernot, Kevin; Pointillart, Fabrice; Rosa, Patrick; Etienne, Mael; Sessoli, Roberta; Gatteschi, Dante

2010-09-21

A Dy-biradical complex was synthesized and characterized down to very low temperature. ac magnetic measurements reveal single molecule magnet behaviour visible without any application of dc field. The transition to the quantum tunneling regime is evidenced. Photophysical and EPR measurements provide evidence of the excellent stability of these complexes in solution.

Proposal for probing energy transfer pathway by single-molecule pump-dump experiment

Science.gov (United States)

Tao, Ming-Jie; Ai, Qing; Deng, Fu-Guo; Cheng, Yuan-Chung

2016-06-01

The structure of Fenna-Matthews-Olson (FMO) light-harvesting complex had long been recognized as containing seven bacteriochlorophyll (BChl) molecules. Recently, an additional BChl molecule was discovered in the crystal structure of the FMO complex, which may serve as a link between baseplate and the remaining seven molecules. Here, we investigate excitation energy transfer (EET) process by simulating single-molecule pump-dump experiment in the eight-molecules complex. We adopt the coherent modified Redfield theory and non-Markovian quantum jump method to simulate EET dynamics. This scheme provides a practical approach of detecting the realistic EET pathway in BChl complexes with currently available experimental technology. And it may assist optimizing design of artificial light-harvesting devices.

Heterobifunctional crosslinkers for tethering single ligand molecules to scanning probes

International Nuclear Information System (INIS)

Riener, Christian K.; Kienberger, Ferry; Hahn, Christoph D.; Buchinger, Gerhard M.; Egwim, Innocent O.C.; Haselgruebler, Thomas; Ebner, Andreas; Romanin, Christoph; Klampfl, Christian; Lackner, Bernd; Prinz, Heino; Blaas, Dieter; Hinterdorfer, Peter; Gruber, Hermann J.

2003-01-01

Single molecule recognition force microscopy (SMRFM) is a versatile atomic force microscopy (AFM) method to probe specific interactions of cognitive molecules on the single molecule level. It allows insights to be gained into interaction potentials and kinetic barriers and is capable of mapping interaction sites with nm positional accuracy. These applications require a ligand to be attached to the AFM tip, preferably by a distensible poly(ethylene glycol) (PEG) chain between the measuring tip and the ligand molecule. The PEG chain greatly facilitates specific binding of the ligand to immobile receptor sites on the sample surface. The present study contributes to tip-PEG-ligand tethering in three ways: (i) a convenient synthetic route was found to prepare NH 2 -PEG-COOH which is the key intermediate for long heterobifunctional crosslinkers; (ii) a variety of heterobifunctional PEG derivatives for tip-PEG-ligand linking were prepared from NH 2 -PEG-COOH; (iii) in particular, a new PEG crosslinker with one thiol-reactive end and one terminal nitrilotriacetic acid (NTA) group was synthesized and successfully used to tether His 6 -tagged protein molecules to AFM tips via noncovalent NTA-Ni 2+ -His 6 bridges. The new crosslinker was applied to link a recombinant His 6 -tagged fragment of the very-low density lipoprotein receptor to the AFM tip whereupon specific docking to the capsid of human rhinovirus particles was observed by force microscopy. In a parallel study, the specific interaction of the small GTPase Ran with the nuclear import receptor importin β1 was studied in detail by SMRFM, using the new crosslinker to link His 6 -tagged Ran to the measuring tip [Nat. Struct. Biol. (2003), 10, 553-557

Single-active-electron potentials for molecules in intense laser fields

DEFF Research Database (Denmark)

Abu-Samha, Mahmoud; Madsen, Lars Bojer

2010-01-01

Single-active-electron potentials are computed for selected molecules, and molecular wave functions with the correct asymptotic behavior are produced. Asymptotic expansion coefficients are extracted from the wave functions and used to compute alignment-dependent ionization yields from molecular...

Statistical analysis of entropy generation in longitudinally finned tube heat exchanger with shell side nanofluid by a single phase approach

Directory of Open Access Journals (Sweden)

Konchada Pavan Kumar

2016-06-01

Full Text Available The presence of nanoparticles in heat exchangers ascertained increment in heat transfer. The present work focuses on heat transfer in a longitudinal finned tube heat exchanger. Experimentation is done on longitudinal finned tube heat exchanger with pure water as working fluid and the outcome is compared numerically using computational fluid dynamics (CFD package based on finite volume method for different flow rates. Further 0.8% volume fraction of aluminum oxide (Al2O3 nanofluid is considered on shell side. The simulated nanofluid analysis has been carried out using single phase approach in CFD by updating the user-defined functions and expressions with thermophysical properties of the selected nanofluid. These results are thereafter compared against the results obtained for pure water as shell side fluid. Entropy generated due to heat transfer and fluid flow is calculated for the nanofluid. Analysis of entropy generation is carried out using the Taguchi technique. Analysis of variance (ANOVA results show that the inlet temperature on shell side has more pronounced effect on entropy generation.

Entropy coherent and entropy convex measures of risk

NARCIS (Netherlands)

Laeven, R.J.A.; Stadje, M.

2013-01-01

We introduce two subclasses of convex measures of risk, referred to as entropy coherent and entropy convex measures of risk. Entropy coherent and entropy convex measures of risk are special cases of φ-coherent and φ-convex measures of risk. Contrary to the classical use of coherent and convex

Population distribution of flexible molecules from maximum entropy analysis using different priors as background information: application to the Φ, Ψ-conformational space of the α-(1-->2)-linked mannose disaccharide present in N- and O-linked glycoproteins.

Science.gov (United States)

Säwén, Elin; Massad, Tariq; Landersjö, Clas; Damberg, Peter; Widmalm, Göran

2010-08-21

The conformational space available to the flexible molecule α-D-Manp-(1-->2)-α-D-Manp-OMe, a model for the α-(1-->2)-linked mannose disaccharide in N- or O-linked glycoproteins, is determined using experimental data and molecular simulation combined with a maximum entropy approach that leads to a converged population distribution utilizing different input information. A database survey of the Protein Data Bank where structures having the constituent disaccharide were retrieved resulted in an ensemble with >200 structures. Subsequent filtering removed erroneous structures and gave the database (DB) ensemble having three classes of mannose-containing compounds, viz., N- and O-linked structures, and ligands to proteins. A molecular dynamics (MD) simulation of the disaccharide revealed a two-state equilibrium with a major and a minor conformational state, i.e., the MD ensemble. These two different conformation ensembles of the disaccharide were compared to measured experimental spectroscopic data for the molecule in water solution. However, neither of the two populations were compatible with experimental data from optical rotation, NMR (1)H,(1)H cross-relaxation rates as well as homo- and heteronuclear (3)J couplings. The conformational distributions were subsequently used as background information to generate priors that were used in a maximum entropy analysis. The resulting posteriors, i.e., the population distributions after the application of the maximum entropy analysis, still showed notable deviations that were not anticipated based on the prior information. Therefore, reparameterization of homo- and heteronuclear Karplus relationships for the glycosidic torsion angles Φ and Ψ were carried out in which the importance of electronegative substituents on the coupling pathway was deemed essential resulting in four derived equations, two (3)J(COCC) and two (3)J(COCH) being different for the Φ and Ψ torsions, respectively. These Karplus relationships are denoted

Single molecule studies of solvent-dependent diffusion and entrapment in poly(dimethylsiloxane) thin films.

Science.gov (United States)

Lange, Jeffrey J; Culbertson, Christopher T; Higgins, Daniel A

2008-12-15

Single molecule microscopic and spectroscopic methods are employed to probe the mobility and physical entrapment of dye molecules in dry and solvent-loaded poly(dimethylsiloxane) (PDMS) films. PDMS films of approximately 220 nm thickness are prepared by spin casting dilute solutions of Sylgard 184 onto glass coverslips, followed by low temperature curing. A perylene diimide dye (BPPDI) is used to probe diffusion and molecule-matrix interactions. Two classes of dye-loaded samples are investigated: (i) those incorporating dye dispersed throughout the films ("in film" samples) and (ii) those in which the dye is restricted primarily to the PDMS surface ("on film" samples). Experiments are performed under dry nitrogen and at various levels of isopropyl alcohol (IPA) loading from the vapor phase. A PDMS-coated quartz-crystal microbalance is employed to monitor solvent loading and drying of the PDMS and to ensure equilibrium conditions are achieved. Single molecules are shown to be predominantly immobile under dry conditions and mostly mobile under IPA-saturated conditions. Quantitative methods for counting the fluorescent spots produced by immobile single molecules in optical images of the samples demonstrate that the population of mobile molecules increases nonlinearly with IPA loading. Even under IPA saturated conditions, the population of fixed molecules is found to be greater than zero and is greatest for "in film" samples. Fluorescence correlation spectroscopy is used to measure the apparent diffusion coefficient for the mobile molecules, yielding a mean value of D = 1.4(+/-0.4) x 10(-8) cm(2)/s that is virtually independent of IPA loading and sample class. It is concluded that a nonzero population of dye molecules is physically entrapped within the PDMS matrix under all conditions. The increase in the population of mobile molecules under high IPA conditions is attributed to the filling of film micropores with solvent, rather than by incorporation of molecularly

Experimental Evidence for Quantum Interference and Vibrationally Induced Decoherence in Single-Molecule Junctions

Science.gov (United States)

Ballmann, Stefan; Härtle, Rainer; Coto, Pedro B.; Elbing, Mark; Mayor, Marcel; Bryce, Martin R.; Thoss, Michael; Weber, Heiko B.

2012-08-01

We analyze quantum interference and decoherence effects in single-molecule junctions both experimentally and theoretically by means of the mechanically controlled break junction technique and density-functional theory. We consider the case where interference is provided by overlapping quasidegenerate states. Decoherence mechanisms arising from electronic-vibrational coupling strongly affect the electrical current flowing through a single-molecule contact and can be controlled by temperature variation. Our findings underline the universal relevance of vibrations for understanding charge transport through molecular junctions.

Single-molecule mechanics of protein-labelled DNA handles

Directory of Open Access Journals (Sweden)

Vivek S. Jadhav

2016-01-01

Full Text Available DNA handles are often used as spacers and linkers in single-molecule experiments to isolate and tether RNAs, proteins, enzymes and ribozymes, amongst other biomolecules, between surface-modified beads for nanomechanical investigations. Custom DNA handles with varying lengths and chemical end-modifications are readily and reliably synthesized en masse, enabling force spectroscopic measurements with well-defined and long-lasting mechanical characteristics under physiological conditions over a large range of applied forces. Although these chemically tagged DNA handles are widely used, their further individual modification with protein receptors is less common and would allow for additional flexibility in grabbing biomolecules for mechanical measurements. In-depth information on reliable protocols for the synthesis of these DNA–protein hybrids and on their mechanical characteristics under varying physiological conditions are lacking in literature. Here, optical tweezers are used to investigate different protein-labelled DNA handles in a microfluidic environment under different physiological conditions. Digoxigenin (DIG-dsDNA-biotin handles of varying sizes (1000, 3034 and 4056 bp were conjugated with streptavidin or neutravidin proteins. The DIG-modified ends of these hybrids were bound to surface-modified polystyrene (anti-DIG beads. Using different physiological buffers, optical force measurements showed consistent mechanical characteristics with long dissociation times. These protein-modified DNA hybrids were also interconnected in situ with other tethered biotinylated DNA molecules. Electron-multiplying CCD (EMCCD imaging control experiments revealed that quantum dot–streptavidin conjugates at the end of DNA handles remain freely accessible. The experiments presented here demonstrate that handles produced with our protein–DNA labelling procedure are excellent candidates for grasping single molecules exposing tags suitable for molecular

Berry-Phase Blockade in Single-Molecule Magnets

Science.gov (United States)

González, Gabriel; Leuenberger, Michael N.

2007-06-01

We formulate the problem of electron transport through a single-molecule magnet (SMM) in the Coulomb blockade regime taking into account topological interference effects for the tunneling of the large spin of a SMM. The interference originates from spin Berry phases associated with different tunneling paths. We show that, in the case of incoherent spin states, it is essential to place the SMM between oppositely spin-polarized source and drain leads in order to detect the spin tunneling in the stationary current, which exhibits topological zeros as a function of the transverse magnetic field.

A Single Molecule Investigation of the Photostability of Quantum Dots

DEFF Research Database (Denmark)

Christensen, Eva Arnspang; Kulatunga, Pasad; Lagerholm, B. Christoffer

2012-01-01

Quantum dots (QDs) are very attractive probes for multi-color fluorescence applications. We report here however that single QDs that are subject to continuous blue excitation from a 100W mercury arc lamp will undergo a continuous blue-switching of the emission wavelength eventually reaching a per...... is especially detrimental for multi-color single molecule applications, as we regularly observe spectral blue-shifts of 50 nm, or more even after only ten seconds of illumination....

Bianthrone in a Single-Molecule Junction: Conductance Switching with a Bistable Molecule Facilitated by Image Charge Effects

DEFF Research Database (Denmark)

Bjørnholm, Thomas

2010-01-01

Bianthrone is a sterically hindered compound that exists in the form of two nonplanar isomers. Our experimental study of single-molecule junctions with bianthrone reveals persistent switching of electric conductance at low temperatures, which can be reasonably associated with molecular isomerizat...

Single-Molecule Electrochemical Gating in Ionic Liquids

DEFF Research Database (Denmark)

Kay, Nicola J.; Higgins, Simon J.; Jeppesen, Jan O.

2012-01-01

The single-molecular conductance of a redox active molecular bridge has been studied in an electrochemical single-molecule transistor configuration in a room-temperature ionic liquid (RTIL). The redox active pyrrolo-tetrathiafulvalene (pTTF) moiety was attached to gold contacts at both ends through...... −(CH2)6S– groups, and gating of the redox state was achieved with the electrochemical potential. The water-free, room-temperature, ionic liquid environment enabled both the monocationic and the previously inaccessible dicationic redox states of the pTTF moiety to be studied in the in situ scanning...... and decreases again as the second redox process is passed. This is described as an “off–on–off–on–off” conductance switching behavior. This molecular conductance vs electrochemical potential relation could be modeled well as a sequential two-step charge transfer process with full or partial vibrational...

Enhancing Single Molecule Imaging in Optofluidics and Microfluidics

Directory of Open Access Journals (Sweden)

Andreas E. Vasdekis

2011-08-01

Full Text Available Microfluidics and optofluidics have revolutionized high-throughput analysis and chemical synthesis over the past decade. Single molecule imaging has witnessed similar growth, due to its capacity to reveal heterogeneities at high spatial and temporal resolutions. However, both resolution types are dependent on the signal to noise ratio (SNR of the image. In this paper, we review how the SNR can be enhanced in optofluidics and microfluidics. Starting with optofluidics, we outline integrated photonic structures that increase the signal emitted by single chromophores and minimize the excitation volume. Turning then to microfluidics, we review the compatible functionalization strategies that reduce noise stemming from non-specific interactions and architectures that minimize bleaching and blinking.

Analysis of thermal systems using the entropy balance method

Energy Technology Data Exchange (ETDEWEB)

Huang, C L.D.; Fartaj, S A; Fenton, D L [Kansas State Univ., Manhattan, KS (United States). Dept. of Mechanical Engineering

1992-04-01

This study investigates the applicability of the second law of thermodynamics using an entropy balance method to analyse and design thermal systems. As examples, the entropy balance method is used to analyse a single stage chiller system and a single stage heat transformer, both with lithium-bromide/water as the working fluid. The entropy method yields not only the same information as is conveyed by the methods of energy and exergy analysis, but it also predicts clearly the influence of irreversibilities of individual components on the coefficient of performance and its effectiveness, based on the process properties, rather than on ambient conditions. Furthermore, this method is capable of presenting the overall distribution of the heat input by displaying the additional heat required to overcome irreversibility of each component without ambiguity. (Author).

Advances in single-molecule magnet surface patterning through microcontact printing

NARCIS (Netherlands)

Mannini, Matteo; Bonacchi, D.; Bonacchi, Daniele; Zobbi, Laura; Piras, Federica M.; Speets, E.A.; Caneschi, Andrea; Cornia, Andrea; Magnani, Agnese; Ravoo, B.J.; Reinhoudt, David; Sessoli, Roberta; Gatteschi, Dante

2005-01-01

We present an implementation of strategies to deposit single-molecule magnets (SMMs) using microcontact printing (uCP). We describe different approaches of CP to print stripes of a sulfur-functionalized dodecamanganese(III,IV) cluster on gold surfaces. Comparison by atomic force microscopy profile

Logarithmic black hole entropy corrections and holographic Renyi entropy

Energy Technology Data Exchange (ETDEWEB)

Mahapatra, Subhash [The Institute of Mathematical Sciences, Chennai (India); KU Leuven - KULAK, Department of Physics, Kortrijk (Belgium)

2018-01-15

The entanglement and Renyi entropies for spherical entangling surfaces in CFTs with gravity duals can be explicitly calculated by mapping these entropies first to the thermal entropy on hyperbolic space and then, using the AdS/CFT correspondence, to the Wald entropy of topological black holes. Here we extend this idea by taking into account corrections to the Wald entropy. Using the method based on horizon symmetries and the asymptotic Cardy formula, we calculate corrections to the Wald entropy and find that these corrections are proportional to the logarithm of the area of the horizon. With the corrected expression for the entropy of the black hole, we then find corrections to the Renyi entropies. We calculate these corrections for both Einstein and Gauss-Bonnet gravity duals. Corrections with logarithmic dependence on the area of the entangling surface naturally occur at the order G{sub D}{sup 0}. The entropic c-function and the inequalities of the Renyi entropy are also satisfied even with the correction terms. (orig.)

Logarithmic black hole entropy corrections and holographic Renyi entropy

International Nuclear Information System (INIS)

Mahapatra, Subhash

2018-01-01

The entanglement and Renyi entropies for spherical entangling surfaces in CFTs with gravity duals can be explicitly calculated by mapping these entropies first to the thermal entropy on hyperbolic space and then, using the AdS/CFT correspondence, to the Wald entropy of topological black holes. Here we extend this idea by taking into account corrections to the Wald entropy. Using the method based on horizon symmetries and the asymptotic Cardy formula, we calculate corrections to the Wald entropy and find that these corrections are proportional to the logarithm of the area of the horizon. With the corrected expression for the entropy of the black hole, we then find corrections to the Renyi entropies. We calculate these corrections for both Einstein and Gauss-Bonnet gravity duals. Corrections with logarithmic dependence on the area of the entangling surface naturally occur at the order G D 0 . The entropic c-function and the inequalities of the Renyi entropy are also satisfied even with the correction terms. (orig.)

Real-time monitoring and manipulation of single bio-molecules in free solution

Energy Technology Data Exchange (ETDEWEB)

Li, Hung-Wing [Iowa State Univ., Ames, IA (United States)

2005-01-01

The observation and manipulation of single biomolecules allow their dynamic behaviors to be studied to provide insight into molecular genetics, biochip assembly, biosensor design, DNA biophysics. In a PDMS/glass microchannel, a nonuniform electroosmotic flow (EOF) was created. By using a scanning confocal fluorescence microscope and total internal-reflection fluorescence microscope (TIRFM), we demonstrated that negatively charged DNA molecules were focused by the nonuniform EOF into a thin layer at the glass surface. This phenomenon was applied to selectively detect target DNA molecules without requiring the separation of excessive probes and can be applied continuously to achieve high throughput. A variable-angle-TIRFM was constructed for imaging single DNA molecule dynamics at a solid/liquid interface. Implications we have are that the measured intensities cannot be used directly to determine the distances of molecules from the surface and the experimental counting results depict the distance-dependent dynamics of molecules near the surface; Molecules at low ionic strengths experience electrostatic repulsion at distances much further away from the surface than the calculated thickness of the electrical double layer. {delta}-DNA was employed as a nanoprobe for different functionalized surfaces to elucidate adsorption in chromatography. The 12-base unpaired ends of this DNA provide exposed purine and pyrimidine groups for adsorption. Patterns of self-assembled monolayers (SAMs) and patterns of metal oxides are generated. By recording the real-time dynamic motion of DNA molecules at the SAMs/aqueous interface, the various parameters governing the retention of an analyte during chromatographic separation can be studied. Even subtle differences among adsorptive forces can be revealed. Dynamic conformational changes of the prosthetic group, flavin adenine dinucleotide (FAD), in flavoprotein NADH peroxidase, in thioredoxin reductase, and in free solution were monitored

One-by-one single-molecule detection of mutated nucleobases by monitoring tunneling current using a DNA tip.

Science.gov (United States)

Bui, Phuc Tan; Nishino, Tomoaki; Shiigi, Hiroshi; Nagaoka, Tsutomu

2015-01-31

A DNA molecule was utilized as a probe tip to achieve single-molecule genetic diagnoses. Hybridization of the probe and target DNAs resulted in electron tunneling along the emergent double-stranded DNA. Simple stationary monitoring of the tunneling current leads to single-molecule DNA detection and discovery of base mismatches and methylation.

Single molecule sequencing-guided scaffolding and correction of draft assemblies.

Science.gov (United States)

Zhu, Shenglong; Chen, Danny Z; Emrich, Scott J

2017-12-06

Although single molecule sequencing is still improving, the lengths of the generated sequences are inevitably an advantage in genome assembly. Prior work that utilizes long reads to conduct genome assembly has mostly focused on correcting sequencing errors and improving contiguity of de novo assemblies. We propose a disassembling-reassembling approach for both correcting structural errors in the draft assembly and scaffolding a target assembly based on error-corrected single molecule sequences. To achieve this goal, we formulate a maximum alternating path cover problem. We prove that this problem is NP-hard, and solve it by a 2-approximation algorithm. Our experimental results show that our approach can improve the structural correctness of target assemblies in the cost of some contiguity, even with smaller amounts of long reads. In addition, our reassembling process can also serve as a competitive scaffolder relative to well-established assembly benchmarks.

Entropy correlation and entanglement for mixed states in an algebraic model

International Nuclear Information System (INIS)

Hou Xiwen; Chen Jinghua; Wan Mingfang; Ma Zhongqi

2009-01-01

As an alternative with potential connections to actual experiments, other than the systems more usually used in the field of entanglement, the dynamics of entropy correlation and entanglement between two anharmonic vibrations in a well-established algebraic model, with parameters extracted from fitting to highly excited spectral experimental results for molecules H 2 O and SO 2 , is studied in terms of the linear entropy and two negativities for various initial states that are respectively taken to be the mixed density matrices of thermal states and squeezed states on each mode. For a suitable parameter in initial states the entropies in two stretches can show positive correlation or anti-correlation. And the linear entropy of each mode is positively correlated with the negativities just for the mixed-squeezed states with small parameters in H 2 O while they do not display any correlation in other cases. For the mixed-squeezed states the negativities exhibit dominantly positive correlations with an effective mutual entropy. The differences in the linear entropy and the negativities between H 2 O and SO 2 are discussed as well. Those are useful for molecular quantum computing and quantum information processing

Probing the local environment of a single OPE3 molecule using inelastic tunneling electron spectroscopy.

Science.gov (United States)

Frisenda, Riccardo; Perrin, Mickael L; van der Zant, Herre S J

2015-01-01

We study single-molecule oligo(phenylene ethynylene)dithiol junctions by means of inelastic electron tunneling spectroscopy (IETS). The molecule is contacted with gold nano-electrodes formed with the mechanically controllable break junction technique. We record the IETS spectrum of the molecule from direct current measurements, both as a function of time and electrode separation. We find that for fixed electrode separation the molecule switches between various configurations, which are characterized by different IETS spectra. Similar variations in the IETS signal are observed during atomic rearrangements upon stretching of the molecular junction. Using quantum chemistry calculations, we identity some of the vibrational modes which constitute a chemical fingerprint of the molecule. In addition, changes can be attributed to rearrangements of the local molecular environment, in particular at the molecule-electrode interface. This study shows the importance of taking into account the interaction with the electrodes when describing inelastic contributions to transport through single-molecule junctions.

Quantifying the Assembly of Multicomponent Molecular Machines by Single-Molecule Total Internal Reflection Fluorescence Microscopy.

Science.gov (United States)

Boehm, E M; Subramanyam, S; Ghoneim, M; Washington, M Todd; Spies, M

2016-01-01

Large, dynamic macromolecular complexes play essential roles in many cellular processes. Knowing how the components of these complexes associate with one another and undergo structural rearrangements is critical to understanding how they function. Single-molecule total internal reflection fluorescence (TIRF) microscopy is a powerful approach for addressing these fundamental issues. In this article, we first discuss single-molecule TIRF microscopes and strategies to immobilize and fluorescently label macromolecules. We then review the use of single-molecule TIRF microscopy to study the formation of binary macromolecular complexes using one-color imaging and inhibitors. We conclude with a discussion of the use of TIRF microscopy to examine the formation of higher-order (i.e., ternary) complexes using multicolor setups. The focus throughout this article is on experimental design, controls, data acquisition, and data analysis. We hope that single-molecule TIRF microscopy, which has largely been the province of specialists, will soon become as common in the tool box of biophysicists and biochemists as structural approaches have become today. © 2016 Elsevier Inc. All rights reserved.

Conductance of single atoms and molecules studied with a scanning tunnelling microscope

International Nuclear Information System (INIS)

Neel, N; Kroeger, J; Limot, L; Berndt, R

2007-01-01

The conductance of single atoms and molecules is investigated with a low-temperature scanning tunnelling microscope. In a controlled and reproducible way, clean Ag(111) surfaces, individual silver atoms on Ag(111) as well as individual C 60 molecules adsorbed on Cu(100) are contacted with the tip of the microscope. Upon contact the conductance changes discontinuously in the case of the tip-surface junction while the tip-atom and tip-molecule junctions exhibit a continuous transition from the tunnelling to the contact regime

Nanomechanical DNA origami 'single-molecule beacons' directly imaged by atomic force microscopy

Science.gov (United States)

Kuzuya, Akinori; Sakai, Yusuke; Yamazaki, Takahiro; Xu, Yan; Komiyama, Makoto

2011-01-01

DNA origami involves the folding of long single-stranded DNA into designed structures with the aid of short staple strands; such structures may enable the development of useful nanomechanical DNA devices. Here we develop versatile sensing systems for a variety of chemical and biological targets at molecular resolution. We have designed functional nanomechanical DNA origami devices that can be used as 'single-molecule beacons', and function as pinching devices. Using 'DNA origami pliers' and 'DNA origami forceps', which consist of two levers ~170 nm long connected at a fulcrum, various single-molecule inorganic and organic targets ranging from metal ions to proteins can be visually detected using atomic force microscopy by a shape transition of the origami devices. Any detection mechanism suitable for the target of interest, pinching, zipping or unzipping, can be chosen and used orthogonally with differently shaped origami devices in the same mixture using a single platform. PMID:21863016

Probing the conductance superposition law in single-molecule circuits with parallel paths.

Science.gov (United States)

Vazquez, H; Skouta, R; Schneebeli, S; Kamenetska, M; Breslow, R; Venkataraman, L; Hybertsen, M S

2012-10-01

According to Kirchhoff's circuit laws, the net conductance of two parallel components in an electronic circuit is the sum of the individual conductances. However, when the circuit dimensions are comparable to the electronic phase coherence length, quantum interference effects play a critical role, as exemplified by the Aharonov-Bohm effect in metal rings. At the molecular scale, interference effects dramatically reduce the electron transfer rate through a meta-connected benzene ring when compared with a para-connected benzene ring. For longer conjugated and cross-conjugated molecules, destructive interference effects have been observed in the tunnelling conductance through molecular junctions. Here, we investigate the conductance superposition law for parallel components in single-molecule circuits, particularly the role of interference. We synthesize a series of molecular systems that contain either one backbone or two backbones in parallel, bonded together cofacially by a common linker on each end. Single-molecule conductance measurements and transport calculations based on density functional theory show that the conductance of a double-backbone molecular junction can be more than twice that of a single-backbone junction, providing clear evidence for constructive interference.

Advances in single-molecule magnet surface patterning through microcontact printing.

Science.gov (United States)

Mannini, Matteo; Bonacchi, Daniele; Zobbi, Laura; Piras, Federica M; Speets, Emiel A; Caneschi, Andrea; Cornia, Andrea; Magnani, Agnese; Ravoo, Bart Jan; Reinhoudt, David N; Sessoli, Roberta; Gatteschi, Dante

2005-07-01

We present an implementation of strategies to deposit single-molecule magnets (SMMs) using microcontact printing microCP). We describe different approaches of microCP to print stripes of a sulfur-functionalized dodecamanganese (III, IV) cluster on gold surfaces. Comparison by atomic force microscopy profile analysis of the patterned structures confirms the formation of a chemically stable single layer of SMMs. Images based on chemical contrast, obtained by time-of-flight secondary ion mass spectrometry, confirm the patterned structure.

Single molecule transcription factor dynamics in the syncytial Drosophila embryo

Science.gov (United States)

Darzacq, Xavier

During early development in the Drosophila embryo, cell fates are determined over the course of just 2 hours with exquisite spatio-temoral precision. One of the key regulators of this process is the transcription factor Bicoid which forms a concentration gradient across the long axis of the embryo. Although Bicoids' primary role is activation at the anterior, where concentrations are highest, it is also known to play a role in the posterior where there are only 100s of molecules per nucleus. Understanding how Bicoid can find its target at such low concentrations has remained intractable, largely due to the inability to perform single molecule imaging in the context of the developing embryo. Here we use lattice light sheet microscopy to overcome the technical barriers of sample thickness and auto-fluorescence to characterize the single molecule dynamics of Bicoid. We find that off-rates do not vary across the embryo and that instead the on-rates are modulated through the formation of clusters that enrich local concentration. This data is contrary to the current concentration dependent model of Bicoid function since local concentration within the nucleus is now a regulated parameter and suggests a previously unknown mechanism for regulation at extremely low concentrations.

Solid-state nanopores for scanning single molecules and mimicking biology

NARCIS (Netherlands)

Kowalczyk, S.W.

2011-01-01

Solid-state nanopores, nanometer-size holes in a thin synthetic membrane, are a versatile tool for the detection and manipulation of charged biomolecules. This thesis describes mostly experimental work on DNA translocation through solid-state nanopores, which we study at the single-molecule level.

Solvation theory to provide a molecular interpretation of the hydrophobic entropy loss of noble-gas hydration

International Nuclear Information System (INIS)

Irudayam, Sheeba Jem; Henchman, Richard H

2010-01-01

An equation for the chemical potential of a dilute aqueous solution of noble gases is derived in terms of energies, force and torque magnitudes, and solute and water coordination numbers, quantities which are all measured from an equilibrium molecular dynamics simulation. Also derived are equations for the Gibbs free energy, enthalpy and entropy of hydration for the Henry's law process, the Ostwald process, and a third proposed process going from an arbitrary concentration in the gas phase to the equivalent mole fraction in aqueous solution which has simpler expressions for the enthalpy and entropy changes. Good agreement with experimental hydration free energies is obtained in the TIP4P and SPC/E water models although the solute's force field appears to affect the enthalpies and entropies obtained. In contrast to other methods, the approach gives a complete breakdown of the entropy for every degree of freedom and makes possible a direct structural interpretation of the well-known entropy loss accompanying the hydrophobic hydration of small non-polar molecules under ambient conditions. The noble-gas solutes experience only a small reduction in their vibrational entropy, with larger solutes experiencing a greater loss. The vibrational and librational entropy components of water actually increase but only marginally, negating any idea of water confinement. The term that contributes the most to the hydrophobic entropy loss is found to be water's orientational term which quantifies the number of orientational minima per water molecule and how many ways the whole hydrogen-bond network can form. These findings help resolve contradictory deductions from experiments that water structure around non-polar solutes is similar to bulk water in some ways but different in others. That the entropy loss lies in water's rotational entropy contrasts with other claims that it largely lies in water's translational entropy, but this apparent discrepancy arises because of different

Single-Molecule Imaging with X-Ray Free-Electron Lasers: Dream or Reality?

KAUST Repository

Fratalocchi, Andrea

2011-03-09

X-ray free-electron lasers (XFEL) are revolutionary photon sources, whose ultrashort, brilliant pulses are expected to allow single-molecule diffraction experiments providing structural information on the atomic length scale of nonperiodic objects. This ultimate goal, however, is currently hampered by several challenging questions basically concerning sample damage, Coulomb explosion, and the role of nonlinearity. By employing an original ab initio approach, we address these issues showing that XFEL-based single-molecule imaging will be only possible with a few-hundred long attosecond pulses, due to significant radiation damage and the formation of preferred multisoliton clusters which reshape the overall electronic density of the molecular system at the femtosecond scale.

Single-Molecule Imaging with X-Ray Free-Electron Lasers: Dream or Reality?

KAUST Repository

Fratalocchi, Andrea; Ruocco, G.

2011-01-01

X-ray free-electron lasers (XFEL) are revolutionary photon sources, whose ultrashort, brilliant pulses are expected to allow single-molecule diffraction experiments providing structural information on the atomic length scale of nonperiodic objects. This ultimate goal, however, is currently hampered by several challenging questions basically concerning sample damage, Coulomb explosion, and the role of nonlinearity. By employing an original ab initio approach, we address these issues showing that XFEL-based single-molecule imaging will be only possible with a few-hundred long attosecond pulses, due to significant radiation damage and the formation of preferred multisoliton clusters which reshape the overall electronic density of the molecular system at the femtosecond scale.

Probing the local environment of a single OPE3 molecule using inelastic tunneling electron spectroscopy

NARCIS (Netherlands)

Frisenda, R.; Perrin, M.L.; Van der Zant, H.S.J.

2015-01-01

We study single-molecule oligo(phenylene ethynylene)dithiol junctions by means of inelastic electron tunneling spectroscopy (IETS). The molecule is contacted with gold nano-electrodes formed with the mechanically controllable break junction technique. We record the IETS spectrum of the molecule from

Mapping Nanoscale Hotspots with Single-Molecule Emitters Assembled into Plasmonic Nanocavities Using DNA Origami

Science.gov (United States)

Chikkaraddy, Rohit; Turek, V. A.; Kongsuwan, Nuttawut; Benz, Felix; Carnegie, Cloudy; van de Goor, Tim; de Nijs, Bart; Demetriadou, Angela; Hess, Ortwin; Keyser, Ulrich F.; Baumberg, Jeremy J.

2018-01-01

Fabricating nanocavities in which optically-active single quantum emitters are precisely positioned, is crucial for building nanophotonic devices. Here we show that self-assembly based on robust DNA-origami constructs can precisely position single molecules laterally within sub-5nm gaps between plasmonic substrates that support intense optical confinement. By placing single-molecules at the center of a nanocavity, we show modification of the plasmon cavity resonance before and after bleaching the chromophore, and obtain enhancements of $\\geq4\\times10^3$ with high quantum yield ($\\geq50$%). By varying the lateral position of the molecule in the gap, we directly map the spatial profile of the local density of optical states with a resolution of $\\pm1.5$ nm. Our approach introduces a straightforward non-invasive way to measure and quantify confined optical modes on the nanoscale.

Mapping Nanoscale Hotspots with Single-Molecule Emitters Assembled into Plasmonic Nanocavities Using DNA Origami.

Science.gov (United States)

Chikkaraddy, Rohit; Turek, V A; Kongsuwan, Nuttawut; Benz, Felix; Carnegie, Cloudy; van de Goor, Tim; de Nijs, Bart; Demetriadou, Angela; Hess, Ortwin; Keyser, Ulrich F; Baumberg, Jeremy J

2018-01-10

Fabricating nanocavities in which optically active single quantum emitters are precisely positioned is crucial for building nanophotonic devices. Here we show that self-assembly based on robust DNA-origami constructs can precisely position single molecules laterally within sub-5 nm gaps between plasmonic substrates that support intense optical confinement. By placing single-molecules at the center of a nanocavity, we show modification of the plasmon cavity resonance before and after bleaching the chromophore and obtain enhancements of ≥4 × 10 3 with high quantum yield (≥50%). By varying the lateral position of the molecule in the gap, we directly map the spatial profile of the local density of optical states with a resolution of ±1.5 nm. Our approach introduces a straightforward noninvasive way to measure and quantify confined optical modes on the nanoscale.

Single-Molecule Flow Platform for the Quantification of Biomolecules Attached to Single Nanoparticles.

Science.gov (United States)

Jung, Seung-Ryoung; Han, Rui; Sun, Wei; Jiang, Yifei; Fujimoto, Bryant S; Yu, Jiangbo; Kuo, Chun-Ting; Rong, Yu; Zhou, Xing-Hua; Chiu, Daniel T

2018-05-15

We describe here a flow platform for quantifying the number of biomolecules on individual fluorescent nanoparticles. The platform combines line-confocal fluorescence detection with near nanoscale channels (1-2 μm in width and height) to achieve high single-molecule detection sensitivity and throughput. The number of biomolecules present on each nanoparticle was determined by deconvolving the fluorescence intensity distribution of single-nanoparticle-biomolecule complexes with the intensity distribution of single biomolecules. We demonstrate this approach by quantifying the number of streptavidins on individual semiconducting polymer dots (Pdots); streptavidin was rendered fluorescent using biotin-Alexa647. This flow platform has high-throughput (hundreds to thousands of nanoparticles detected per second) and requires minute amounts of sample (∼5 μL at a dilute concentration of 10 pM). This measurement method is an additional tool for characterizing synthetic or biological nanoparticles.

Maximum entropy production rate in quantum thermodynamics

Energy Technology Data Exchange (ETDEWEB)

Beretta, Gian Paolo, E-mail: beretta@ing.unibs.i [Universita di Brescia, via Branze 38, 25123 Brescia (Italy)

2010-06-01

In the framework of the recent quest for well-behaved nonlinear extensions of the traditional Schroedinger-von Neumann unitary dynamics that could provide fundamental explanations of recent experimental evidence of loss of quantum coherence at the microscopic level, a recent paper [Gheorghiu-Svirschevski 2001 Phys. Rev. A 63 054102] reproposes the nonlinear equation of motion proposed by the present author [see Beretta G P 1987 Found. Phys. 17 365 and references therein] for quantum (thermo)dynamics of a single isolated indivisible constituent system, such as a single particle, qubit, qudit, spin or atomic system, or a Bose-Einstein or Fermi-Dirac field. As already proved, such nonlinear dynamics entails a fundamental unifying microscopic proof and extension of Onsager's reciprocity and Callen's fluctuation-dissipation relations to all nonequilibrium states, close and far from thermodynamic equilibrium. In this paper we propose a brief but self-contained review of the main results already proved, including the explicit geometrical construction of the equation of motion from the steepest-entropy-ascent ansatz and its exact mathematical and conceptual equivalence with the maximal-entropy-generation variational-principle formulation presented in Gheorghiu-Svirschevski S 2001 Phys. Rev. A 63 022105. Moreover, we show how it can be extended to the case of a composite system to obtain the general form of the equation of motion, consistent with the demanding requirements of strong separability and of compatibility with general thermodynamics principles. The irreversible term in the equation of motion describes the spontaneous attraction of the state operator in the direction of steepest entropy ascent, thus implementing the maximum entropy production principle in quantum theory. The time rate at which the path of steepest entropy ascent is followed has so far been left unspecified. As a step towards the identification of such rate, here we propose a possible

Exploring the energy landscape of biopolymers using single molecule force spectroscopy and molecular simulations

OpenAIRE

Hyeon, Changbong

2010-01-01

In recent years, single molecule force techniques have opened a new avenue to decipher the folding landscapes of biopolymers by allowing us to watch and manipulate the dynamics of individual proteins and nucleic acids. In single molecule force experiments, quantitative analyses of measurements employing sound theoretical models and molecular simulations play central role more than any other field. With a brief description of basic theories for force mechanics and molecular simulation techniqu...

Probing static disorder in Arrhenius kinetics by single-molecule force spectroscopy.

Science.gov (United States)

Kuo, Tzu-Ling; Garcia-Manyes, Sergi; Li, Jingyuan; Barel, Itay; Lu, Hui; Berne, Bruce J; Urbakh, Michael; Klafter, Joseph; Fernández, Julio M

2010-06-22

The widely used Arrhenius equation describes the kinetics of simple two-state reactions, with the implicit assumption of a single transition state with a well-defined activation energy barrier DeltaE, as the rate-limiting step. However, it has become increasingly clear that the saddle point of the free-energy surface in most reactions is populated by ensembles of conformations, leading to nonexponential kinetics. Here we present a theory that generalizes the Arrhenius equation to include static disorder of conformational degrees of freedom as a function of an external perturbation to fully account for a diverse set of transition states. The effect of a perturbation on static disorder is best examined at the single-molecule level. Here we use force-clamp spectroscopy to study the nonexponential kinetics of single ubiquitin proteins unfolding under force. We find that the measured variance in DeltaE shows both force-dependent and independent components, where the force-dependent component scales with F(2), in excellent agreement with our theory. Our study illustrates a novel adaptation of the classical Arrhenius equation that accounts for the microscopic origins of nonexponential kinetics, which are essential in understanding the rapidly growing body of single-molecule data.

ENTROPY FUNCTIONAL FOR CONTINUOUS SYSTEMS OF FINITE ENTROPY

Institute of Scientific and Technical Information of China (English)

M. Rahimi A. Riazi

2012-01-01

In this article,we introduce the concept of entropy functional for continuous systems on compact metric spaces,and prove some of its properties.We also extract the Kolmogorov entropy from the entropy functional.

Single-molecule studies of DNA transcription using atomic force microscopy

International Nuclear Information System (INIS)

Billingsley, Daniel J; Crampton, Neal; Thomson, Neil H; Bonass, William A; Kirkham, Jennifer

2012-01-01