Manually operatable on-chip bistable pneumatic microstructures for microfluidic manipulations.

Science.gov (United States)

Chen, Arnold; Pan, Tingrui

2014-09-07

Bistable microvalves are of particular interest because of their distinct nature of requiring energy consumption only during the transition between the open and closed states. This characteristic can be highly advantageous in reducing the number of external inputs and the complexity of control circuitries since microfluidic devices as contemporary lab-on-a-chip platforms are transferring from research settings to low-resource environments with high integrability and a small form factor. In this paper, we first present manually operatable, on-chip bistable pneumatic microstructures (BPMs) for microfluidic manipulation. The structural design and operation of the BPM devices can be readily integrated into any pneumatically powered microfluidic network consisting of pneumatic and fluidic channels. It is mainly composed of a vacuum activation chamber (VAC) and a pressure release chamber (PRC), of which users have direct control through finger pressing to switch either to the bistable vacuum state (VS) or the atmospheric state (AS). We have integrated multiple BPM devices into a 4-to-1 microfluidic multiplexor to demonstrate on-chip digital flow switching from different sources. Furthermore, we have shown its clinical relevance in a point-of-care diagnostic chip that processes blood samples to identify the distinct blood types (A/B/O) on-chip.

Capacitance variation induced by microfluidic two-phase flow across insulated interdigital electrodes in lab-on-chip devices.

Science.gov (United States)

Dong, Tao; Barbosa, Cátia

2015-01-26

Microfluidic two-phase flow detection has attracted plenty of interest in various areas of biology, medicine and chemistry. This work presents a capacitive sensor using insulated interdigital electrodes (IDEs) to detect the presence of droplets in a microchannel. This droplet sensor is composed of a glass substrate, patterned gold electrodes and an insulation layer. A polydimethylsiloxane (PDMS) cover bonded to the multilayered structure forms a microchannel. Capacitance variation induced by the droplet passage was thoroughly investigated with both simulation and experimental work. Olive oil and deionized water were employed as the working fluids in the experiments to demonstrate the droplet sensor. The results show a good sensitivity of the droplet with the appropriate measurement connection. This capacitive droplet sensor is promising to be integrated into a lab-on-chip device for in situ monitoring/counting of droplets or bubbles.

Revisiting lab-on-a-chip technology for drug discovery.

Science.gov (United States)

Neuži, Pavel; Giselbrecht, Stefan; Länge, Kerstin; Huang, Tony Jun; Manz, Andreas

2012-08-01

The field of microfluidics or lab-on-a-chip technology aims to improve and extend the possibilities of bioassays, cell biology and biomedical research based on the idea of miniaturization. Microfluidic systems allow more accurate modelling of physiological situations for both fundamental research and drug development, and enable systematic high-volume testing for various aspects of drug discovery. Microfluidic systems are in development that not only model biological environments but also physically mimic biological tissues and organs; such 'organs on a chip' could have an important role in expediting early stages of drug discovery and help reduce reliance on animal testing. This Review highlights the latest lab-on-a-chip technologies for drug discovery and discusses the potential for future developments in this field.

IFSA: a microfluidic chip-platform for frit-based immunoassay protocols

Science.gov (United States)

Hlawatsch, Nadine; Bangert, Michael; Miethe, Peter; Becker, Holger; Gärtner, Claudia

2013-03-01

Point-of-care diagnostics (POC) is one of the key application fields for lab-on-a-chip devices. While in recent years much of the work has concentrated on integrating complex molecular diagnostic assays onto a microfluidic device, there is a need to also put comparatively simple immunoassay-type protocols on a microfluidic platform. In this paper, we present the development of a microfluidic cartridge using an immunofiltration approach. In this method, the sandwich immunoassay takes place in a porous frit on which the antibodies have immobilized. The device is designed to be able to handle three samples in parallel and up to four analytical targets per sample. In order to meet the critical cost targets for the diagnostic market, the microfluidic chip has been designed and manufactured using high-volume manufacturing technologies in mind. Validation experiments show comparable sensitivities in comparison with conventional immunofiltration kits.

Nanophotonic lab-on-a-chip platforms including novel bimodal interferometers, microfluidics and grating couplers.

Science.gov (United States)

Duval, Daphné; González-Guerrero, Ana Belén; Dante, Stefania; Osmond, Johann; Monge, Rosa; Fernández, Luis J; Zinoviev, Kirill E; Domínguez, Carlos; Lechuga, Laura M

2012-05-08

One of the main limitations for achieving truly lab-on-a-chip (LOC) devices for point-of-care diagnosis is the incorporation of the "on-chip" detection. Indeed, most of the state-of-the-art LOC devices usually require complex read-out instrumentation, losing the main advantages of portability and simplicity. In this context, we present our last advances towards the achievement of a portable and label-free LOC platform with highly sensitive "on-chip" detection by using nanophotonic biosensors. Bimodal waveguide interferometers fabricated by standard silicon processes have been integrated with sub-micronic grating couplers for efficient light in-coupling, showing a phase resolution of 6.6 × 10(-4)× 2π rad and a limit of detection of 3.3 × 10(-7) refractive index unit (RIU) in bulk. A 3D network of SU-8 polymer microfluidics monolithically assembled at the wafer-level was included, ensuring perfect sealing and compact packaging. To overcome some of the drawbacks inherent to interferometric read-outs, a novel all-optical wavelength modulation system has been implemented, providing a linear response and a direct read-out of the phase variation. Sensitivity, specificity and reproducibility of the wavelength modulated BiMW sensor has been demonstrated through the label-free immunodetection of the human hormone hTSH at picomolar level using a reliable biofunctionalization process.

A piezo-ring-on-chip microfluidic device for simple and low-cost mass spectrometry interfacing.

Science.gov (United States)

Tsao, Chia-Wen; Lei, I-Chao; Chen, Pi-Yu; Yang, Yu-Liang

2018-02-12

Mass spectrometry (MS) interfacing technology provides the means for incorporating microfluidic processing with post MS analysis. In this study, we propose a simple piezo-ring-on-chip microfluidic device for the controlled spraying of MALDI-MS targets. This device uses a low-cost, commercially-available ring-shaped piezoelectric acoustic atomizer (piezo-ring) directly integrated into a polydimethylsiloxane microfluidic device to spray the sample onto the MS target substrate. The piezo-ring-on-chip microfluidic device's design, fabrication, and actuation, and its pulsatile pumping effects were evaluated. The spraying performance was examined by depositing organic matrix samples onto the MS target substrate by using both an automatic linear motion motor, and manual deposition. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was performed to analyze the peptide samples on the MALDI target substrates. Using our technique, model peptides with 10 -6 M concentration can be successfully detected. The results also indicate that the piezo-ring-on-chip approach forms finer matrix crystals and presents better MS signal uniformity with little sample consumption compared to the conventional pipetting method.

Lab-On-a-Chip Application Development (LOCAD): Bridging Technology Readiness for Exploration

Science.gov (United States)

Spearing, Scott F.; Jenkins, Andy

2004-01-01

At Marshall Space Flight Center we have established a capability to investigate the use of microfluidics for space flight. The Lab-On-a-Chip Application Development (LOCAD) team has created a program for advancing Technology Readiness Levels (TRL) of 1 and 2 to TRL 6 and 7, quickly and economically for Lab-On-a-Chip (LOC) applications. Scientists and engineers can utilize LOCAD'S process to efficiently learn about microfluidics and determine if microfluidics is applicable to their needs. Once the applicability has been determined, LOCAD can then perform tests to develop the new fluidic protocols which are different from macro-scale chemical reaction protocols. With this information new micro-fluidic devices can be created and tested. Currently, LOCAD is focused on using microfluidics for both Environmental Monitoring & Control, and Medical Systems. Eventually, handheld portable units utilizing LOC technology will perform rapid tests to determine water quality, and microbial contamination levels. Since LOC technology is drastically reduced in physical size, it thereby reduces power, weight, volume, and sample requirements, a big advantage considering the resource constraints associated with spaceflight. Another one of LOCAD's current activities is the development of a microfluidic system to aid in the search for life on Mars.

Additive manufacturing of lab-on-a-chip devices: promises and challenges

Science.gov (United States)

Zhu, Feng; Macdonald, Niall P.; Cooper, Jonathan M.; Wlodkowic, Donald

2013-12-01

This work describes a preliminary investigation of commercially available 3D printing technologies for rapid prototyping and low volume fabrication of Lab-on-a-Chip devices. The main motivation of the work was to use off-the-shelf 3D printing methods in order to rapidly and inexpensively build microfluidic devices with complex geometric features and reduce the need to use clear room environment and conventional microfabrication techniques. Both multi-jet modelling (MJM) and stereolithography (SLA) processes were explored. MJM printed devices were fabricated using a HD3500+ (3D Systems) high-definition printer using a thermo-polymer VisiJet Crystal (3D Systems) substratum that allows for a z-axis resolution of 16 μm and 25 μm x-y accuracy. SLA printed devices were produced using a Viper Pro (3D Systems) stereolithography system using Watershed 11122XC (DSM Somos) and Dreve Fototec 7150 Clear (Dreve Otoplastik GmbH) resins which allow for a z-axis resolution of 50 μm and 25 μm x-y accuracy. Fabrication results compared favourably with other forms of rapid prototyping such as laser cut PMMA devices and PDMS moulded microfluidic devices of the same design. Both processes allowed for fabrication of monolithic, optically transparent devices with features in the 100 μm range requiring minimal post-processing. Optical polymer qualities following different post-processing methods were also tested in both brightfield and fluorescence imaging of transgenic zebrafish embryos. Finally, we show that only ethanol-treated Dreve Fototec 7150 Clear resign proved to be non-toxic to human cell lines and fish embryos in fish toxicity assays (FET) requiring further investigation of 3D printing materials.

Multi-color fluorescent DNA analysis in an integrated optofluidic lab-on-a-chip

OpenAIRE

Dongre, C.; van Weerd, J.; van Weeghel, R.; Martinez-Vazquez, R.; Osellame, R.; Cerullo, G.; Besselink, G.A.J.; van den Vlekkert, H.H.; Hoekstra, Hugo; Pollnau, Markus

2010-01-01

Sorting and sizing of DNA molecules within the human genome project has enabled the genetic mapping of various illnesses. By employing tiny lab-on-a-chip devices for such DNA analysis, integrated DNA sequencing and genetic diagnostics have become feasible. However, such diagnostic chips typically lack integrated sensing capability. We address this issue by combining microfluidic capillary electrophoresis with laser-induced fluorescence detection resulting in optofluidic integration towards an...

A multilevel Lab on chip platform for DNA analysis.

Science.gov (United States)

Marasso, Simone Luigi; Giuri, Eros; Canavese, Giancarlo; Castagna, Riccardo; Quaglio, Marzia; Ferrante, Ivan; Perrone, Denis; Cocuzza, Matteo

2011-02-01

Lab-on-chips (LOCs) are critical systems that have been introduced to speed up and reduce the cost of traditional, laborious and extensive analyses in biological and biomedical fields. These ambitious and challenging issues ask for multi-disciplinary competences that range from engineering to biology. Starting from the aim to integrate microarray technology and microfluidic devices, a complex multilevel analysis platform has been designed, fabricated and tested (All rights reserved-IT Patent number TO2009A000915). This LOC successfully manages to interface microfluidic channels with standard DNA microarray glass slides, in order to implement a complete biological protocol. Typical Micro Electro Mechanical Systems (MEMS) materials and process technologies were employed. A silicon/glass microfluidic chip and a Polydimethylsiloxane (PDMS) reaction chamber were fabricated and interfaced with a standard microarray glass slide. In order to have a high disposable system all micro-elements were passive and an external apparatus provided fluidic driving and thermal control. The major microfluidic and handling problems were investigated and innovative solutions were found. Finally, an entirely automated DNA hybridization protocol was successfully tested with a significant reduction in analysis time and reagent consumption with respect to a conventional protocol.

Fabrication of Polymerase Chain Reaction Plastic Lab-on-a-Chip Device for Rapid Molecular Diagnoses

Directory of Open Access Journals (Sweden)

Kieu The Loan Trinh

2016-05-01

Full Text Available Purpose: We aim to fabricate a thermoplastic poly(methylmethacrylate (PMMA Lab-on-a-Chip device to perform continuous- flow polymerase chain reactions (PCRs for rapid molecular detection of foodborne pathogen bacteria. Methods: A miniaturized plastic device was fabricated by utilizing PMMA substrates mediated by poly(dimethylsiloxane interfacial coating, enabling bonding under mild conditions, and thus avoiding the deformation or collapse of microchannels. Surface characterizations were carried out and bond strength was measured. The feasibility of the Lab-on-a-Chip device for performing on-chip PCR utilizing a lab-made, portable dual heater was evaluated. The results were compared with those obtained using a commercially available thermal cycler. Results: A PMMA Lab-on-a-Chip device was designed and fabricated for conducting PCR using foodborne pathogens as sample targets. A robust bond was established between the PMMA substrates, which is essential for performing miniaturized PCR on plastic. The feasibility of on-chip PCR was evaluated using Escherichia coli O157:H7 and Cronobacter condimenti, two worldwide foodborne pathogens, and the target amplicons were successfully amplified within 25 minutes. Conclusions: In this study, we present a novel design of a low-cost and high-throughput thermoplastic PMMA Lab-on-a-Chip device for conducting microscale PCR, and we enable rapid molecular diagnoses of two important foodborne pathogens in minute resolution using this device. In this regard, the introduced highly portable system design has the potential to enable PCR investigations of many diseases quickly and accurately.

Programmable lab-on-a-chip system for single cell analysis

Science.gov (United States)

Thalhammer, S.

2009-05-01

The collection, selection, amplification and detection of minimum genetic samples became a part of everyday life in medical and biological laboratories, to analyze DNA-fragments of pathogens, patient samples and traces on crime scenes. About a decade ago, a handful of researchers began discussing an intriguing idea. Could the equipment needed for everyday chemistry and biology procedures be shrunk to fit on a chip in the size of a fingernail? Miniature devices for, say, analysing DNA and proteins should be faster and cheaper than conventional versions. Lab-on-a-chip is an advanced technology that integrates a microfluidic system on a microscale chip device. The "laboratory" is created by means of channels, mixers, reservoirs, diffusion chambers, integrated electrodes, pumps, valves and more. With lab-ona- chip technology, complete laboratories on a square centimetre can be created. Here, a multifunctional programmable Lab-on-a-Chip driven by nanofluidics and controlled by surface acoustic waves (SAW) is presented. This system combines serial DNA-isolation-, amplification- and array-detection-process on a modified glass-platform. The fluid actuation is controlled via SAW by interdigital transducers implemented in the chemical modified chip surface. The chemical surface modification allows fluid handling in the sub-microliter range. Minute amount of sample material is extracted by laser-based microdissection out of e.g. histological sections at the single cell level. A few picogram of genetic material are isolated and transferred via a low-pressure transfer system (SPATS) onto the chip. Subsequently the genetic material inside single droplets, which behave like "virtual" beaker, is transported to the reaction and analysis centers on the chip surface via surface acoustic waves, mainly known as noise dumping filters in mobile phones. At these "biological reactors" the genetic material is processed, e.g. amplified via polymerase chain reaction methods, and genetically

Microfluidic Platform for the Long-Term On-Chip Cultivation of Mammalian Cells for Lab-On-A-Chip Applications.

Science.gov (United States)

Bunge, Frank; Driesche, Sander van den; Vellekoop, Michael J

2017-07-10

Lab-on-a-Chip (LoC) applications for the long-term analysis of mammalian cells are still very rare due to the lack of convenient cell cultivation devices. The difficulties are the integration of suitable supply structures, the need of expensive equipment like an incubator and sophisticated pumps as well as the choice of material. The presented device is made out of hard, but non-cytotoxic materials (silicon and glass) and contains two vertical arranged membranes out of hydrogel. The porous membranes are used to separate the culture chamber from two supply channels for gases and nutrients. The cells are fed continuously by diffusion through the membranes without the need of an incubator and low requirements on the supply of medium to the assembly. The diffusion of oxygen is modelled in order to find the optimal dimensions of the chamber. The chip is connected via 3D-printed holders to the macroscopic world. The holders are coated with Parlyene C to ensure that only biocompatible materials are in contact with the culture medium. The experiments with MDCK-cells show the successful seeding inside the chip, culturing and passaging. Consequently, the presented platform is a step towards Lab-on-a-Chip applications that require long-term cultivation of mammalian cells.

Universal lab-on-a-chip platform for complex, perfused 3D cell cultures

Science.gov (United States)

Sonntag, F.; Schmieder, F.; Ströbel, J.; Grünzner, S.; Busek, M.; Günther, K.; Steege, T.; Polk, C.; Klotzbach, U.

2016-03-01

The miniaturization, rapid prototyping and automation of lab-on-a-chip technology play nowadays a very important role. Lab-on-a-chip technology is successfully implemented not only for environmental analysis and medical diagnostics, but also as replacement of animals used for the testing of substances in the pharmaceutical and cosmetics industries. For that purpose the Fraunhofer IWS and partners developed a lab-on-a-chip platform for perfused cell-based assays in the last years, which includes different micropumps, valves, channels, reservoirs and customized cell culture modules. This technology is already implemented for the characterization of different human cell cultures and organoids, like skin, liver, endothelium, hair follicle and nephron. The advanced universal lab-on-a-chip platform for complex, perfused 3D cell cultures is divided into a multilayer basic chip with integrated micropump and application-specific 3D printed cell culture modules. Moreover a technology for surface modification of the printed cell culture modules by laser micro structuring and a complex and flexibly programmable controlling device based on an embedded Linux system was developed. A universal lab-on-a-chip platform with an optional oxygenator and a cell culture module for cubic scaffolds as well as first cell culture experiments within the cell culture device will be presented. The module is designed for direct interaction with robotic dispenser systems. This offers the opportunity to combine direct organ printing of cells and scaffolds with the microfluidic cell culture module. The characterization of the developed system was done by means of Micro-Particle Image Velocimetry (μPIV) and an optical oxygen measuring system.

Microfluidic Devices for Terahertz Spectroscopy of Live Cells Toward Lab-on-a-Chip Applications

Directory of Open Access Journals (Sweden)

Qi Tang

2016-04-01

Full Text Available THz spectroscopy is an emerging technique for studying the dynamics and interactions of cells and biomolecules, but many practical challenges still remain in experimental studies. We present a prototype of simple and inexpensive cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells are transported, trapped and concentrated into the THz exposure region by applying an AC bias signal while the chip maintains a steady temperature at 37 °C by resistive heating. We conduct some preliminary experiments on E. coli and T-cell solution and compare the transmission spectra of empty channels, channels filled with aqueous media only, and channels filled with aqueous media with un-concentrated and concentrated cells.

Design, microfabrication, and characterization of a moulded PDMS/SU-8 inkjet dispenser for a Lab-on-a-Printer platform technology with disposable microfluidic chip.

Science.gov (United States)

Bsoul, Anas; Pan, Sheng; Cretu, Edmond; Stoeber, Boris; Walus, Konrad

2016-08-16

In this paper, we present a disposable inkjet dispenser platform technology and demonstrate the Lab-on-a-Printer concept, an extension of the ubiquitous Lab-on-a-Chip concept, whereby microfluidic modules are directly integrated into the printhead. The concept is demonstrated here through the integration of an inkjet dispenser and a microfluidic mixer enabling control over droplet composition from a single nozzle in real-time during printing. The inkjet dispenser is based on a modular design platform that enables the low-cost microfluidic component and the more expensive actuation unit to be easily separated, allowing for the optional disposal of the former and reuse of the latter. To limit satellite droplet formation, a hydrophobic-coated and tapered micronozzle was microfabricated and integrated with the fluidics to realize the dispenser. The microfabricated devices generated droplets with diameters ranging from 150-220 μm, depending mainly on the orifice diameter, with printing rates up to 8000 droplets per second. The inkjet dispenser is capable of dispensing materials with a viscosity up to ∼19 mPa s. As a demonstration of the inkjet dispenser function and application, we have printed type I collagen seeded with human liver carcinoma cells (cell line HepG2), to form patterned biological structures.

Recent advances in particle and droplet manipulation for lab-on-a-chip devices based on surface acoustic waves.

Science.gov (United States)

Wang, Zhuochen; Zhe, Jiang

2011-04-07

Manipulation of microscale particles and fluid liquid droplets is an important task for lab-on-a-chip devices for numerous biological researches and applications, such as cell detection and tissue engineering. Particle manipulation techniques based on surface acoustic waves (SAWs) appear effective for lab-on-a-chip devices because they are non-invasive, compatible with soft lithography micromachining, have high energy density, and work for nearly any type of microscale particles. Here we review the most recent research and development of the past two years in SAW based particle and liquid droplet manipulation for lab-on-a-chip devices including particle focusing and separation, particle alignment and patterning, particle directing, and liquid droplet delivery.

Single cells as experimentation units in lab-on-a-chip devices

NARCIS (Netherlands)

le Gac, Severine; van den Berg, Albert

'Lab-on-a-chip' technology (LOC) has now reached a mature state and is employed commonly in research in the life sciences. LOC devices make novel experimentation possible while providing a sophisticated environment for cellular investigation. As a next step, we introduce here the concept of a

A self-contained fully-enclosed microfluidic cartridge for lab on a chip.

Science.gov (United States)

Yobas, Levent; Cheow, Lih Feng; Tang, Kum-Cheong; Yong, Shien-Eit; Ong, Eleana Kye-Zheng; Wong, Lionel; Teo, William Cheng-Yong; Ji, Hongmiao; Rafeah, Siti; Yu, Chen

2009-12-01

We describe a self-contained fully-enclosed cartridge for lab-on-a-chip applications where sample and reagents can be applied sequentially as is performed in a heterogeneous immunoassay, or nucleic acid extraction. Both the self-contained and fully-enclosed features of the cartridge are sought to ensure its safe use in the field by unskilled staff. Simplicity in cartridge design and operation is obtained via adopting a valveless concept whereby reagents are stored and used in the form of liquid plugs isolated by air spacers around a fluidic loop. Functional components integrated in the loop include a microfluidic chip specific to the target application, a novel peristaltic pump to displace the liquid plugs, and a pair of removable tubing segments where one is used to introduce biological sample and while the other is to collect eluant. The novel pump is fabricated through soft-lithography technique and works by pinching a planar channel under stainless-steel ball bearings that have been magnetically loaded. The utility of the cartridge is demonstrated for automated extraction and purification of nucleic acids (DNA) from a cell lysate on a battery-operated portable system. The cartridge shown here can be further extended to sample-in-answer-out diagnostic tests.

Field-programmable lab-on-a-chip based on microelectrode dot array architecture.

Science.gov (United States)

Wang, Gary; Teng, Daniel; Lai, Yi-Tse; Lu, Yi-Wen; Ho, Yingchieh; Lee, Chen-Yi

2014-09-01

The fundamentals of electrowetting-on-dielectric (EWOD) digital microfluidics are very strong: advantageous capability in the manipulation of fluids, small test volumes, precise dynamic control and detection, and microscale systems. These advantages are very important for future biochip developments, but the development of EWOD microfluidics has been hindered by the absence of: integrated detector technology, standard commercial components, on-chip sample preparation, standard manufacturing technology and end-to-end system integration. A field-programmable lab-on-a-chip (FPLOC) system based on microelectrode dot array (MEDA) architecture is presented in this research. The MEDA architecture proposes a standard EWOD microfluidic component called 'microelectrode cell', which can be dynamically configured into microfluidic components to perform microfluidic operations of the biochip. A proof-of-concept prototype FPLOC, containing a 30 × 30 MEDA, was developed by using generic integrated circuits computer aided design tools, and it was manufactured with standard low-voltage complementary metal-oxide-semiconductor technology, which allows smooth on-chip integration of microfluidics and microelectronics. By integrating 900 droplet detection circuits into microelectrode cells, the FPLOC has achieved large-scale integration of microfluidics and microelectronics. Compared to the full-custom and bottom-up design methods, the FPLOC provides hierarchical top-down design approach, field-programmability and dynamic manipulations of droplets for advanced microfluidic operations.

Organ/body-on-a-chip based on microfluidic technology for drug discovery.

Science.gov (United States)

Kimura, Hiroshi; Sakai, Yasuyuki; Fujii, Teruo

2018-02-01

Although animal experiments are indispensable for preclinical screening in the drug discovery process, various issues such as ethical considerations and species differences remain. To solve these issues, cell-based assays using human-derived cells have been actively pursued. However, it remains difficult to accurately predict drug efficacy, toxicity, and organs interactions, because cultivated cells often do not retain their original organ functions and morphologies in conventional in vitro cell culture systems. In the μTAS research field, which is a part of biochemical engineering, the technologies of organ-on-a-chip, based on microfluidic devices built using microfabrication, have been widely studied recently as a novel in vitro organ model. Since it is possible to physically and chemically mimic the in vitro environment by using microfluidic device technology, maintenance of cellular function and morphology, and replication of organ interactions can be realized using organ-on-a-chip devices. So far, functions of various organs and tissues, such as the lung, liver, kidney, and gut have been reproduced as in vitro models. Furthermore, a body-on-a-chip, integrating multi organ functions on a microfluidic device, has also been proposed for prediction of organ interactions. We herein provide a background of microfluidic systems, organ-on-a-chip, Body-on-a-chip technologies, and their challenges in the future. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Lab-on-a-Chip: Frontier Science in the Classroom

Science.gov (United States)

Wietsma, Jan Jaap; van der Veen, Jan T.; Buesink, Wilfred; van den Berg, Albert; Odijk, Mathieu

2018-01-01

Lab-on-a-chip technology is brought into the classroom through development of a lesson series with hands-on practicals. Students can discover the principles of microfluidics with different practicals covering laminar flow, micromixing, and droplet generation, as well as trapping and counting beads. A quite affordable novel production technique…

CMOS capacitive sensors for lab-on-chip applications a multidisciplinary approach

CERN Document Server

Ghafar-Zadeh, Ebrahim

2010-01-01

The main components of CMOS capacitive biosensors including sensing electrodes, bio-functionalized sensing layer, interface circuitries and microfluidic packaging are verbosely explained in chapters 2-6 after a brief introduction on CMOS based LoCs in Chapter 1. CMOS Capacitive Sensors for Lab-on-Chip Applications is written in a simple pedagogical way. It emphasises practical aspects of fully integrated CMOS biosensors rather than mathematical calculations and theoretical details. By using CMOS Capacitive Sensors for Lab-on-Chip Applications, the reader will have circuit design methodologies,

A multi-channel clogging-resistant lab-on-a-chip cell counter and analyzer

International Nuclear Information System (INIS)

Dai, Jie; Yang, Kecheng; Chiu, Yu-Jui; Wu, Tsung-Feng; Lian, Ian; Lo, Yu-Hwa

2016-01-01

Early signs of diseases can be revealed from cell detection in biofluids, such as detection of white blood cells (WBCs) in the peritoneal fluid for peritonitis. A lab-on-a-chip microfluidic device offers an attractive platform for such applications because of its small size, low cost, and ease of use provided the device can meet the performance requirements which many existing LoC devices fail to satisfy. We report an integrated microfluidic device capable of accurately counting low concentration of white blood cells in peritoneal fluid at 150 μl min −1 to offer an accurate (<3% error) and fast (∼10 min/run) WBC count. Utilizing the self-regulating hydrodynamic properties and a unique architecture in the design, the device can achieve higher flow rate (500–1000 μl min −1 ), continuous running for over 5 h without clogging, as well as excellent signal quality for unambiguous WBC count and WBC classification for certain diseases. These properties make the device a promising candidate for point-of-care applications. (paper)

Research Progress of Microfluidic Chips Preparation and its Optical Element

Directory of Open Access Journals (Sweden)

Feng WANG

2014-03-01

Full Text Available Microfluidic technology is the emerging technologies in researching fluid channel and related applications in the micro and nano-scale space. Microfluidic chip is a new miniaturized rapid analysis platform by microfluidic technology, it has many characteristics such as liquid flow control, minimal reagent consumption, rapid analysis, which is widely used in physics, chemistry, biology, and engineering science and other fields, it has strong interdisciplinary. This paper mainly discusses research progress of materials used for microfluidic chips and the devices based on microfluidic technology, including microfluidic chip, microfluidic optical devices, microfluidic laser preparation, microfluidic chip applications, focusing on the quasi-molecular laser processing technology and femtosecond laser processing technology in the microfluidic devices preparation, and make development prospects for it.

Magnetically Driven Micromachines Created by Two-Photon Microfabrication and Selective Electroless Magnetite Plating for Lab-on-a-Chip Applications

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Tommaso Zandrini

2017-01-01

Full Text Available We propose a novel method to fabricate three-dimensional magnetic microparts, which can be integrated in functional microfluidic networks and lab-on-a-chip devices, by the combination of two-photon microfabrication and selective electroless plating. In our experiments, magnetic microparts could be successfully fabricated by optimizing various experimental conditions of electroless plating. In addition, energy dispersive X-ray spectrometry (EDS clarified that iron oxide nanoparticles were deposited onto the polymeric microstructure site-selectively. We also fabricated magnetic microrotors which could smoothly rotate using common laboratory equipment. Since such magnetic microparts can be remotely driven with an external magnetic field, our fabrication process can be applied to functional lab-on-a-chip devices for analytical and biological applications.

Lab-on-a-Chip Based Protein Crystallization

Science.gov (United States)

vanderWoerd, Mark J.; Brasseur, Michael M.; Spearing, Scott F.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

We are developing a novel technique with which we will grow protein crystals in very small volumes, utilizing chip-based, microfluidic ("LabChip") technology. This development, which is a collaborative effort between NASA's Marshall Space Flight Center and Caliper Technologies Corporation, promises a breakthrough in the field of protein crystal growth. Our initial results obtained from two model proteins, Lysozyme and Thaumatin, show that it is feasible to dispense and adequately mix protein and precipitant solutions on a nano-liter scale. The mixtures have shown crystal growth in volumes in the range of 10 nanoliters to 5 microliters. In addition, large diffraction quality crystals were obtained by this method. X-ray data from these crystals were shown to be of excellent quality. Our future efforts will include the further development of protein crystal growth with LabChip(trademark) technology for more complex systems. We will initially address the batch growth method, followed by the vapor diffusion method and the liquid-liquid diffusion method. The culmination of these chip developments is to lead to an on orbit protein crystallization facility on the International Space Station. Structural biologists will be invited to utilize the on orbit Iterative Biological Crystallization facility to grow high quality macromolecular crystals in microgravity.

Hybrid Integrated Silicon Microfluidic Platform for Fluorescence Based Biodetection

Directory of Open Access Journals (Sweden)

André Darveau

2007-09-01

Full Text Available The desideratum to develop a fully integrated Lab-on-a-chip device capable ofrapid specimen detection for high throughput in-situ biomedical diagnoses and Point-of-Care testing applications has called for the integration of some of the novel technologiessuch as the microfluidics, microphotonics, immunoproteomics and Micro ElectroMechanical Systems (MEMS. In the present work, a silicon based microfluidic device hasbeen developed for carrying out fluorescence based immunoassay. By hybrid attachment ofthe microfluidic device with a Spectrometer-on-chip, the feasibility of synthesizing anintegrated Lab-on-a-chip type device for fluorescence based biosensing has beendemonstrated. Biodetection using the microfluidic device has been carried out usingantigen sheep IgG and Alexafluor-647 tagged antibody particles and the experimentalresults prove that silicon is a compatible material for the present application given thevarious advantages it offers such as cost-effectiveness, ease of bulk microfabrication,superior surface affinity to biomolecules, ease of disposability of the device etc., and is thussuitable for fabricating Lab-on-a-chip type devices.

Photonics-on-a-chip: recent advances in integrated waveguides as enabling detection elements for real-world, lab-on-a-chip biosensing applications.

Science.gov (United States)

Washburn, Adam L; Bailey, Ryan C

2011-01-21

By leveraging advances in semiconductor microfabrication technologies, chip-integrated optical biosensors are poised to make an impact as scalable and multiplexable bioanalytical measurement tools for lab-on-a-chip applications. In particular, waveguide-based optical sensing technology appears to be exceptionally amenable to chip integration and miniaturization, and, as a result, the recent literature is replete with examples of chip-integrated waveguide sensing platforms developed to address a wide range of contemporary analytical challenges. As an overview of the most recent advances within this dynamic field, this review highlights work from the last 2-3 years in the areas of grating-coupled, interferometric, photonic crystal, and microresonator waveguide sensors. With a focus towards device integration, particular emphasis is placed on demonstrations of biosensing using these technologies within microfluidically controlled environments. In addition, examples of multiplexed detection and sensing within complex matrices--important features for real-world applicability--are given special attention.

Study of a novel cell lysis method with titanium dioxide for Lab-on-a-Chip devices.

Science.gov (United States)

Wan, Weijie; Yeow, John T W

2011-06-01

In this paper, a novel method is proposed and demonstrated to be able to lyse gram-negative (E. coli) bacteria cells for Lab-on-a-Chip applications. The proposed method incorporates using titanium dioxide particles as photocatalysts and a miniaturized UV LED array as an excitation light source to perform cell lysis on microchips. The experimental result demonstrates the feasibility of the proposed prototype device. The working device suggests an inexpensive, easy to be fabricated and effective way for microchip cell lysis. The miniaturized UV LED array and the microchip with a reaction chamber can be easily integrated with other functional components to form a customized whole Lab-on-a-Chip system.

Microfluidic Lab-on-a-Chip Platforms: Requirements, Characteristics and Applications

Science.gov (United States)

Mark, D.; Haeberle, S.; Roth, G.; von Stetten, F.; Zengerle, R.

This review summarizes recent developments in microfluidic platform approaches. In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the implementation of different application-specific (bio-) chemical processes, automated by microfluidic process integration [1]. A brief introduction into technical advances, major market segments and promising applications is followed by a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electro-kinetics, electrowetting, surface acoustic waves, and systems for massively parallel analysis. The review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposable, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols.

Biosensors-on-chip: a topical review

International Nuclear Information System (INIS)

Chen, Sensen; Shamsi, Mohtashim H

2017-01-01

This review will examine the integration of two fields that are currently at the forefront of science, i.e. biosensors and microfluidics. As a lab-on-a-chip (LOC) technology, microfluidics has been enriched by the integration of various detection tools for analyte detection and quantitation. The application of such microfluidic platforms is greatly increased in the area of biosensors geared towards point-of-care diagnostics. Together, the merger of microfluidics and biosensors has generated miniaturized devices for sample processing and sensitive detection with quantitation. We believe that microfluidic biosensors (biosensors-on-chip) are essential for developing robust and cost effective point-of-care diagnostics. This review is relevant to a variety of disciplines, such as medical science, clinical diagnostics, LOC technologies including MEMs/NEMs, and analytical science. Specifically, this review will appeal to scientists working in the two overlapping fields of biosensors and microfluidics, and will also help new scientists to find their directions in developing point-of-care devices. (topical review)

Discrete microfluidics based on aluminum nitride surface acoustic wave devices

OpenAIRE

Zhou, J.; Pang, H.F.; Garcia-Gancedo, L.; Iborra, E.; Clement, M.; De Miguel-Ramos, M.; Jin, H.; Luo, J.K.; Smith, S.; Dong, S.R.; Wang, D.M.; Fu, Y.Q.

2015-01-01

To date, most surface acoustic wave (SAW) devices have been made from bulk piezoelectric materials, such as quartz, lithium niobate or lithium tantalite. These bulk materials are brittle, less easily integrated with electronics for control and signal processing, and difficult to realize multiple wave modes or apply complex electrode designs. Using thin film SAWs makes it convenient to integrate microelectronics and multiple sensing or microfluidics techniques into a lab-on-a-chip with low cos...

Microfluidic CODES: a scalable multiplexed electronic sensor for orthogonal detection of particles in microfluidic channels.

Science.gov (United States)

Liu, Ruxiu; Wang, Ningquan; Kamili, Farhan; Sarioglu, A Fatih

2016-04-21

Numerous biophysical and biochemical assays rely on spatial manipulation of particles/cells as they are processed on lab-on-a-chip devices. Analysis of spatially distributed particles on these devices typically requires microscopy negating the cost and size advantages of microfluidic assays. In this paper, we introduce a scalable electronic sensor technology, called microfluidic CODES, that utilizes resistive pulse sensing to orthogonally detect particles in multiple microfluidic channels from a single electrical output. Combining the techniques from telecommunications and microfluidics, we route three coplanar electrodes on a glass substrate to create multiple Coulter counters producing distinct orthogonal digital codes when they detect particles. We specifically design a digital code set using the mathematical principles of Code Division Multiple Access (CDMA) telecommunication networks and can decode signals from different microfluidic channels with >90% accuracy through computation even if these signals overlap. As a proof of principle, we use this technology to detect human ovarian cancer cells in four different microfluidic channels fabricated using soft lithography. Microfluidic CODES offers a simple, all-electronic interface that is well suited to create integrated, low-cost lab-on-a-chip devices for cell- or particle-based assays in resource-limited settings.

Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

Directory of Open Access Journals (Sweden)

Ana Rubina Perestrelo

2015-12-01

Full Text Available Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called “organ-on-a-chip” technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.

Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

Science.gov (United States)

Perestrelo, Ana Rubina; Águas, Ana C. P.; Rainer, Alberto; Forte, Giancarlo

2015-01-01

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called “organ-on-a-chip” technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field. PMID:26690442

Optial sensing systems for microfluidic devices: a review

NARCIS (Netherlands)

Kuswandi, Bambang; Nuriman, [Unknown; Huskens, Jurriaan; Verboom, Willem

2007-01-01

This review deals with the application of optical sensing systems for microfluidic devices. In the “off-chip approach” macro-scale optical infrastructure is coupled, while the “on-chip approach” comprises the integration of micro-optical functions into microfluidic devices. The current progress of

A Lab on a chip device for rapid identification of Avian Influenza virus by on-chip sample preparation and solid phase PCR

DEFF Research Database (Denmark)

Yi, Sun; Dhumpa, Raghuram; Bang, Dang Duong

2009-01-01

In this paper, we describe a novel lab-on-a-chip device for fast AIV screening by integrating DNA microarray-based solid phase PCR on microchip. The device can handle viral samples in an automatic way. Moreover, multiplex PCR and sequence detection are done in one-step, which greatly simplifies...

Microfluidic Devices for Forensic DNA Analysis: A Review.

Science.gov (United States)

Bruijns, Brigitte; van Asten, Arian; Tiggelaar, Roald; Gardeniers, Han

2016-08-05

Microfluidic devices may offer various advantages for forensic DNA analysis, such as reduced risk of contamination, shorter analysis time and direct application at the crime scene. Microfluidic chip technology has already proven to be functional and effective within medical applications, such as for point-of-care use. In the forensic field, one may expect microfluidic technology to become particularly relevant for the analysis of biological traces containing human DNA. This would require a number of consecutive steps, including sample work up, DNA amplification and detection, as well as secure storage of the sample. This article provides an extensive overview of microfluidic devices for cell lysis, DNA extraction and purification, DNA amplification and detection and analysis techniques for DNA. Topics to be discussed are polymerase chain reaction (PCR) on-chip, digital PCR (dPCR), isothermal amplification on-chip, chip materials, integrated devices and commercially available techniques. A critical overview of the opportunities and challenges of the use of chips is discussed, and developments made in forensic DNA analysis over the past 10-20 years with microfluidic systems are described. Areas in which further research is needed are indicated in a future outlook.

Advances in piezoelectric thin films for acoustic biosensors, acoustofluidics and lab-on-chip applications

OpenAIRE

Fu, Yong Qing; Luo, Jack; Nguyen, Nam-Trung; Walton, Anthony; Flewitt, Andrew; Zu, Xiao-Tao; Li, Yifan; McHale, Glen; Matthews, Allan; Iborra, Enrique; Du, Hejun; Milne, William

2017-01-01

Recently, piezoelectric thin films including zinc oxide (ZnO) and aluminium nitride (AlN) have found a broad range of lab-on-chip applications such as biosensing, particle/cell concentrating, sorting/patterning, pumping, mixing, nebulisation and jetting. Integrated acoustic wave sensing/microfluidic devices have been fabricated by depositing these piezoelectric films onto a number of substrates such as silicon, ceramics, diamond, quartz, glass, and more recently also polymer, metallic foils a...

Miniaturization of environmental chemical assays in flowing systems: The lab-on-a-valve approach vis-à-vis lab-on-a-chip microfluidic devices

DEFF Research Database (Denmark)

Miró, Manuel; Hansen, Elo Harald

2007-01-01

The analytical capabilities of the microminiaturised lab-on-a-valve (LOV) module integrated into a microsequential injection (muSI) fluidic system in terms of analytical chemical performance, microfluidic handling and on-line sample processing are compared to those of the micro total analysis...... and the kinetics of the chemical reactions at will, LOV allows accommodation of reactions which, at least at the present stage, are not feasible by application of microfluidic LOC systems. Thus, in LOV one may take advantage of kinetic discriminations schemes, where even subtle differences in reactions...... are utilized for analytical purposes. Furthemore, it is also feasible to handle multi-step sequential reactions of divergent kinetics; to conduct multi-parametric determinations without manifold reconfiguration by utilization of the inherent open architecture of the micromachined unit for the implementation...

Lab-on a-Chip

Science.gov (United States)

1999-01-01

Labs on chips are manufactured in many shapes and sizes and can be used for numerous applications, from medical tests to water quality monitoring to detecting the signatures of life on other planets. The eight holes on this chip are actually ports that can be filled with fluids or chemicals. Tiny valves control the chemical processes by mixing fluids that move in the tiny channels that look like lines, connecting the ports. Scientists at NASA's Marshall Space Flight Center (MSFC) in Huntsville, Alabama designed this chip to grow biological crystals on the International Space Station (ISS). Through this research, they discovered that this technology is ideally suited for solving the challenges of the Vision for Space Exploration. For example, thousands of chips the size of dimes could be loaded on a Martian rover looking for biosignatures of past or present life. Other types of chips could be placed in handheld devices used to monitor microbes in water or to quickly conduct medical tests on astronauts. The portable, handheld Lab-on-a Chip Application Development Portable Test System (LOCAD-PTS) made its debut flight aboard Discovery during the STS-116 mission launched December 9, 2006. The system allowed crew members to monitor their environment for problematic contaminants such as yeast, mold, and even E.coli, and salmonella. Once LOCAD-PTS reached the ISS, the Marshall team continued to manage the experiment, monitoring the study from a console in the Payload Operations Center at MSFC. The results of these studies will help NASA researchers refine the technology for future Moon and Mars missions. (NASA/MSFC/D.Stoffer)

Integration of micro-optics and microfluidics in a glass chip by fs-laser for optofluidic applications

Science.gov (United States)

Osellame, Roberto; Martinez, Rebeca; Laporta, Paolo; Ramponi, Roberta; Cerullo, Giulio

2009-02-01

A lab-on-a-chip (LOC) is a device that incorporates in a single substrate the functionalities of a biological laboratory, i.e. a network of fluidic channels, reservoirs, valves, pumps and sensors, all with micrometer dimensions. Its main advantages are the possibility of working with small samples quantities (from nano- to picoliters), high sensitivity, speed of analysis and the possibility of measurement automation and standardization. They are becoming the most powerful tools of analytical chemistry with a broad application in life sciences, biotechnology and drug development. The next technological challenge of LOCs is direct on-chip integration of photonic functionalities for sensing of biomolecules flowing in the microchannels. Ultrafast laser processing of the bulk of a dielectric material is a very flexible and simple method to produce photonic devices inside microfluidic chips for capillary electrophoresis (CE) or chemical microreactors. By taking advantage of the unique three-dimensional capabilities of this fabrication technique, more complex functionalities, such as splitters or Mach-Zehnder interferometers, can be implemented. In this work we report on the use of femtosecond laser pulses to fabricate photonic devices (as waveguides, splitters and interferometers) inside commercial CE chips, without affecting the manufacturing procedure of the microfluidic part of the device. The fabrication of single waveguides intersecting the channels allows one to perform absorption or Laser Induced Fluorescence (LIF) sensing of the molecules separated inside the microchannels. Waveguide splitters are used for multipoint excitation of the microfluidic channel for parallel or higher sensitivity measurements. Finally, Mach-Zehnder interferometers are used for label-free sensing of the samples flowing in the microfluidic channels by means of refractive index changes detection.

‘Chip-olate’ and dry-film resists for efficient fabrication, singulation and sealing of microfluidic chips

Science.gov (United States)

Temiz, Yuksel; Delamarche, Emmanuel

2014-09-01

This paper describes a technique for high-throughput fabrication and efficient singulation of chips having closed microfluidic structures and takes advantage of dry-film resists (DFRs) for efficient sealing of capillary systems. The technique is illustrated using 4-inch Si/SiO2 wafers. Wafers carrying open microfluidic structures are partially diced to about half of their thickness. Treatments such as surface cleaning are done at wafer-level, then the structures are sealed using low-temperature (45 °C) lamination of a DFR that is pre-patterned using a craft cutter, and ready-to-use chips are finally separated manually like a chocolate bar by applying a small force (≤ 4 N). We further show that some DFRs have low auto-fluorescence at wavelengths typically used for common fluorescent dyes and that mechanical properties of some DFRs allow for the lamination of 200 μm wide microfluidic structures with negligible sagging (~1 μm). The hydrophilicity (advancing contact angle of ~60°) of the DFR supports autonomous capillary-driven flow without the need for additional surface treatment of the microfluidic chips. Flow rates from 1 to 5 µL min-1 are generated using different geometries of channels and capillary pumps. In addition, the ‘chip-olate’ technique is compatible with the patterning of capture antibodies on DFR for use in immunoassays. We believe this technique to be applicable to the fabrication of a wide range of microfluidic and lab-on-a-chip devices and to offer a viable alternative to many labor-intensive processes that are currently based on wafer bonding techniques or on the molding of poly(dimethylsiloxane) (PDMS) layers.

Recent Progress in Lab-on-a-Chip Technology and Its Potential Application to Clinical Diagnoses

Directory of Open Access Journals (Sweden)

Nae Yoon Lee

2013-03-01

Full Text Available We present the construction of the lab-on-a-chip (LOC system, a state-of-the-art technology that uses polymer materials (i.e., poly[dimethylsiloxane] for the miniaturization of conventional laboratory apparatuses, and show the potential use of these microfluidic devices in clinical applications. In particular, we introduce the independent unit components of the LOC system and demonstrate how each component can be functionally integrated into one monolithic system for the realization of a LOC system. In specific, we demonstrate microscale polymerase chain reaction with the use of a single heater, a microscale sample injection device with a disposable plastic syringe and a strategy for device assembly under environmentally mild conditions assisted by surface modification techniques. In this way, we endeavor to construct a totally integrated, disposable microfluidic system operated by a single mode, the pressure, which can be applied on-site with enhanced device portability and disposability and with simple and rapid operation for medical and clinical diagnoses, potentially extending its application to urodynamic studies in molecular level.

Making the invisible visible: a microfluidic chip using a low refractive index polymer.

Science.gov (United States)

Hanada, Yasutaka; Ogawa, Tatsuya; Koike, Kazuhiko; Sugioka, Koji

2016-07-07

Microfluidic frameworks known as micro-total-analysis-systems or lab-on-a-chip have become versatile tools in cell biology research, since functional biochips are able to streamline dynamic observations of various cells. Glass or polymers are generally used as the substrate due to their high transparency, chemical stability and cost-effectiveness. However, these materials are not well suited for the microscopic observation of cell migration at the fluid boundary due to the refractive index mismatch between the medium and the biochip material. For this reason, we have developed a new method of fabricating three-dimensional (3D) microfluidic chips made of the low refractive index fluoric polymer CYTOP. This novel fabrication procedure involves the use of a femtosecond laser for direct writing, followed by wet etching with a dilute fluorinated solvent and annealing, to create high-quality 3D microfluidic chips inside a polymer substrate. A microfluidic chip made in this manner enabled us to more clearly observe the flagellum motion of a Dinoflagellate moving in circles near the fluid surface compared to the observations possible using conventional microfluidic chips. We believe that CYTOP microfluidic chips made using this new method may allow more detailed analysis of various cell migrations near solid boundaries.

Microfluidic Diatomite Analytical Devices for Illicit Drug Sensing with ppb-Level Sensitivity.

Science.gov (United States)

Kong, Xianming; Chong, Xinyuan; Squire, Kenny; Wang, Alan X

2018-04-15

The escalating research interests in porous media microfluidics, such as microfluidic paper-based analytical devices, have fostered a new spectrum of biomedical devices for point-of-care (POC) diagnosis and biosensing. In this paper, we report microfluidic diatomite analytical devices (μDADs), which consist of highly porous photonic crystal biosilica channels, as an innovative lab-on-a-chip platform to detect illicit drugs. The μDADs in this work are fabricated by spin-coating and tape-stripping diatomaceous earth on regular glass slides with cross section of 400×30µm 2 . As the most unique feature, our μDADs can simultaneously perform on-chip chromatography to separate small molecules from complex biofluidic samples and acquire the surface-enhanced Raman scattering spectra of the target chemicals with high specificity. Owing to the ultra-small dimension of the diatomite microfluidic channels and the photonic crystal effect from the fossilized diatom frustules, we demonstrate unprecedented sensitivity down to part-per-billion (ppb) level when detecting pyrene (1ppb) from mixed sample with Raman dye and cocaine (10 ppb) from human plasma. This pioneering work proves the exclusive advantage of μDADs as emerging microfluidic devices for chemical and biomedical sensing, especially for POC drug screening.

Real-time studies of chemical reactions in lab-on-a-chip devices

NARCIS (Netherlands)

Brivio, M.

2005-01-01

The realization of a lab-on-a-chip system in which chemical reactions are carried out in a continuous flow mode and monitored on-line by a suitable analytical technique is the main topic of this thesis. Two types of a lab-on-a-chip were realized, both using mass spectrometry (MS) as the on-line

Laser micromachining of biofactory-on-a-chip devices

Science.gov (United States)

Burt, Julian P.; Goater, Andrew D.; Hayden, Christopher J.; Tame, John A.

2002-06-01

Excimer laser micromachining provides a flexible means for the manufacture and rapid prototyping of miniaturized systems such as Biofactory-on-a-Chip devices. Biofactories are miniaturized diagnostic devices capable of characterizing, manipulating, separating and sorting suspension of particles such as biological cells. Such systems operate by exploiting the electrical properties of microparticles and controlling particle movement in AC non- uniform stationary and moving electric fields. Applications of Biofactory devices are diverse and include, among others, the healthcare, pharmaceutical, chemical processing, environmental monitoring and food diagnostic markets. To achieve such characterization and separation, Biofactory devices employ laboratory-on-a-chip type components such as complex multilayer microelectrode arrays, microfluidic channels, manifold systems and on-chip detection systems. Here we discuss the manufacturing requirements of Biofactory devices and describe the use of different excimer laser micromachined methods both in stand-alone processes and also in conjunction with conventional fabrication processes such as photolithography and thermal molding. Particular attention is given to the production of large area multilayer microelectrode arrays and the manufacture of complex cross-section microfluidic channel systems for use in simple distribution and device interfacing.

Femtosecond laser microfabrication of optical waveguides in commercial microfluidic lab-on-a-chip

NARCIS (Netherlands)

Osellame, R.; Martinez-Vazquez, R.; Ramponi, R.; Cerullo, G.; Dongre, C.; Dekker, R.; Hoekstra, Hugo; Pollnau, Markus

One of the main challenges of lab-on-a-chip technology is the on-chip integration of photonic functionalities by manufacturing optical waveguides for sensing biomolecules flowing in the microchannels. Such integrated approach has many advantages over traditional free-space optical sensing, such as

Various on-chip sensors with microfluidics for biological applications.

Science.gov (United States)

Lee, Hun; Xu, Linfeng; Koh, Domin; Nyayapathi, Nikhila; Oh, Kwang W

2014-09-12

In this paper, we review recent advances in on-chip sensors integrated with microfluidics for biological applications. Since the 1990s, much research has concentrated on developing a sensing system using optical phenomena such as surface plasmon resonance (SPR) and surface-enhanced Raman scattering (SERS) to improve the sensitivity of the device. The sensing performance can be significantly enhanced with the use of microfluidic chips to provide effective liquid manipulation and greater flexibility. We describe an optical image sensor with a simpler platform for better performance over a larger field of view (FOV) and greater depth of field (DOF). As a new trend, we review consumer electronics such as smart phones, tablets, Google glasses, etc. which are being incorporated in point-of-care (POC) testing systems. In addition, we discuss in detail the current optical sensing system integrated with a microfluidic chip.

Dynamic magnetic particle actuation for integrated lab-on-chip biosensing

NARCIS (Netherlands)

Jong, de A.M.; Reenen, van A.; Prins, M.W.J.

2014-01-01

The demand for easy to use and cost effective medical technologies inspires scientists to develop innovative lab-on-chip technologies for in-vitro diagnostic testing. We study the use of magnetic particles actuated by magnetic fields to perform different microfluidic handling steps of an integrated

Lab-on-a-chip based total-phosphorus analysis device utilizing a photocatalytic reaction

Science.gov (United States)

Jung, Dong Geon; Jung, Daewoong; Kong, Seong Ho

2018-02-01

A lab-on-a-chip (LOC) device for total phosphorus (TP) analysis was fabricated for water quality monitoring. Many commercially available TP analysis systems used to estimate water quality have good sensitivity and accuracy. However, these systems also have many disadvantages such as bulky size, complex pretreatment processes, and high cost, which limit their application. In particular, conventional TP analysis systems require an indispensable pretreatment step, in which the fluidic analyte is heated to 120 °C for 30 min to release the dissolved phosphate, because many phosphates are soluble in water at a standard temperature and pressure. In addition, this pretreatment process requires elevated pressures of up to 1.1 kg cm-2 in order to prevent the evaporation of the heated analyte. Because of these limiting conditions required by the pretreatment processes used in conventional systems, it is difficult to miniaturize TP analysis systems. In this study, we employed a photocatalytic reaction in the pretreatment process. The reaction was carried out by illuminating a photocatalytic titanium dioxide (TiO2) surface formed in a microfluidic channel with ultraviolet (UV) light. This pretreatment process does not require elevated temperatures and pressures. By applying this simplified, photocatalytic-reaction-based pretreatment process to a TP analysis system, greater degrees of freedom are conferred to the design and fabrication of LOC devices for TP monitoring. The fabricated LOC device presented in this paper was characterized by measuring the TP concentration of an unknown sample, and comparing the results with those measured by a conventional TP analysis system. The TP concentrations of the unknown sample measured by the proposed LOC device and the conventional TP analysis system were 0.018 mgP/25 mL and 0.019 mgP/25 mL, respectively. The experimental results revealed that the proposed LOC device had a performance comparable to the conventional bulky TP analysis

‘Chip-olate’ and dry-film resists for efficient fabrication, singulation and sealing of microfluidic chips

International Nuclear Information System (INIS)

Temiz, Yuksel; Delamarche, Emmanuel

2014-01-01

This paper describes a technique for high-throughput fabrication and efficient singulation of chips having closed microfluidic structures and takes advantage of dry-film resists (DFRs) for efficient sealing of capillary systems. The technique is illustrated using 4-inch Si/SiO 2 wafers. Wafers carrying open microfluidic structures are partially diced to about half of their thickness. Treatments such as surface cleaning are done at wafer-level, then the structures are sealed using low-temperature (45 °C) lamination of a DFR that is pre-patterned using a craft cutter, and ready-to-use chips are finally separated manually like a chocolate bar by applying a small force (≤ 4 N). We further show that some DFRs have low auto-fluorescence at wavelengths typically used for common fluorescent dyes and that mechanical properties of some DFRs allow for the lamination of 200 μm wide microfluidic structures with negligible sagging (∼1 μm). The hydrophilicity (advancing contact angle of ∼60°) of the DFR supports autonomous capillary-driven flow without the need for additional surface treatment of the microfluidic chips. Flow rates from 1 to 5 µL min -1 are generated using different geometries of channels and capillary pumps. In addition, the ‘chip-olate’ technique is compatible with the patterning of capture antibodies on DFR for use in immunoassays. We believe this technique to be applicable to the fabrication of a wide range of microfluidic and lab-on-a-chip devices and to offer a viable alternative to many labor-intensive processes that are currently based on wafer bonding techniques or on the molding of poly(dimethylsiloxane) (PDMS) layers. (technical note)

Reagent-loaded plastic microfluidic chips for detecting homocysteine

International Nuclear Information System (INIS)

Suk, Ji Won; Jang, Jae-Young; Cho, Jun-Hyeong

2008-01-01

This report describes the preliminary study on plastic microfluidic chips with pre-loaded reagents for detecting homocysteine (Hcy). All reagents needed in an Hcy immunoassay were included in a microfluidic chip to remove tedious assay steps. A simple and cost-effective bonding method was developed to realize reagent-loaded microfluidic chips. This technique uses an intermediate layer between two plastic substrates by selectively patterning polydimethylsiloxane (PDMS) on the embossed surface of microchannels and fixing the substrates under pressure. Using this bonding method, the competitive immunoassay for SAH, a converted form of Hcy, was performed without any damage to reagents in chips, and the results showed that the fluorescent signal from antibody antigen binding decreased as the SAH concentration increased. Based on the SAH immunoassay, whole immunoassay steps for Hcy detection were carried out in plastic microfluidic chips with all necessary reagents. These experiments demonstrated the feasibility of the Hcy immunoassay in microfluidic devices

Towards autonomous lab-on-a-chip devices for cell phone biosensing.

Science.gov (United States)

Comina, Germán; Suska, Anke; Filippini, Daniel

2016-03-15

Modern cell phones are a ubiquitous resource with a residual capacity to accommodate chemical sensing and biosensing capabilities. From the different approaches explored to capitalize on such resource, the use of autonomous disposable lab-on-a-chip (LOC) devices-conceived as only accessories to complement cell phones-underscores the possibility to entirely retain cell phones' ubiquity for distributed biosensing. The technology and principles exploited for autonomous LOC devices are here selected and reviewed focusing on their potential to serve cell phone readout configurations. Together with this requirement, the central aspects of cell phones' resources that determine their potential for analytical detection are examined. The conversion of these LOC concepts into universal architectures that are readable on unaccessorized phones is discussed within this context. Copyright © 2015 Elsevier B.V. All rights reserved.

Acoustofluidics 14: Applications of acoustic streaming in microfluidic devices.

Science.gov (United States)

Wiklund, Martin; Green, Roy; Ohlin, Mathias

2012-07-21

In part 14 of the tutorial series "Acoustofluidics--exploiting ultrasonic standing wave forces and acoustic streaming in microfluidic systems for cell and particle manipulation", we provide a qualitative description of acoustic streaming and review its applications in lab-on-a-chip devices. The paper covers boundary layer driven streaming, including Schlichting and Rayleigh streaming, Eckart streaming in the bulk fluid, cavitation microstreaming and surface-acoustic-wave-driven streaming.

Flash μ-fluidics: a rapid prototyping method for fabricating microfluidic devices

KAUST Repository

Buttner, Ulrich

2016-08-01

Microfluidics has advanced in terms of design and structures; however, fabrication methods are time-consuming or expensive relative to facility costs and equipment needed. This work demonstrates a fast and economically viable 2D/3D maskless digital light-projection method based on a stereolithography process. Unlike other fabrication methods, one exposure step is used to form the whole device. Flash microfluidics is achieved by incorporating bonding and channel fabrication of complex structures in just 2.5 s to 4 s and by fabricating channel heights between 25 μm and 150 μm with photopolymer resin. The features of this fabrication technique, such as time and cost saving and easy fabrication, are used to build devices that are mostly needed in microfluidic/lab-on-chip systems. Due to the fast production method and low initial setup costs, the process could be used for point of care applications. © 2016 The Royal Society of Chemistry.

Flash μ-fluidics: a rapid prototyping method for fabricating microfluidic devices

KAUST Repository

Buttner, Ulrich; Sivashankar, Shilpa; Agambayev, Sumeyra; Mashraei, Yousof; Salama, Khaled N.

2016-01-01

Microfluidics has advanced in terms of design and structures; however, fabrication methods are time-consuming or expensive relative to facility costs and equipment needed. This work demonstrates a fast and economically viable 2D/3D maskless digital light-projection method based on a stereolithography process. Unlike other fabrication methods, one exposure step is used to form the whole device. Flash microfluidics is achieved by incorporating bonding and channel fabrication of complex structures in just 2.5 s to 4 s and by fabricating channel heights between 25 μm and 150 μm with photopolymer resin. The features of this fabrication technique, such as time and cost saving and easy fabrication, are used to build devices that are mostly needed in microfluidic/lab-on-chip systems. Due to the fast production method and low initial setup costs, the process could be used for point of care applications. © 2016 The Royal Society of Chemistry.

Various On-Chip Sensors with Microfluidics for Biological Applications

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Hun Lee

2014-09-01

Full Text Available In this paper, we review recent advances in on-chip sensors integrated with microfluidics for biological applications. Since the 1990s, much research has concentrated on developing a sensing system using optical phenomena such as surface plasmon resonance (SPR and surface-enhanced Raman scattering (SERS to improve the sensitivity of the device. The sensing performance can be significantly enhanced with the use of microfluidic chips to provide effective liquid manipulation and greater flexibility. We describe an optical image sensor with a simpler platform for better performance over a larger field of view (FOV and greater depth of field (DOF. As a new trend, we review consumer electronics such as smart phones, tablets, Google glasses, etc. which are being incorporated in point-of-care (POC testing systems. In addition, we discuss in detail the current optical sensing system integrated with a microfluidic chip.

NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae.

Directory of Open Access Journals (Sweden)

Chunxiao Hu

Full Text Available Genetic and chemical biology screens of C. elegans have been of enormous benefit in providing fundamental insight into neural function and neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. Here we make a significant addition to this repertoire through the design of a semi-automated microfluidic device, NeuroChip, which has been optimised for selecting worms based on the electrophysiological features of the pharyngeal neural network. We demonstrate this device has the capability to sort mutant from wild-type worms based on high definition extracellular electrophysiological recordings. NeuroChip resolves discrete differences in excitatory, inhibitory and neuromodulatory components of the neural network from individual animals. Worms may be fed into the device consecutively from a reservoir and recovered unharmed. It combines microfluidics with integrated electrode recording for sequential trapping, restraining, recording, releasing and recovering of C. elegans. Thus mutant worms may be selected, recovered and propagated enabling mutagenesis screens based on an electrophysiological phenotype. Drugs may be rapidly applied during the recording thus permitting compound screening. For toxicology, this analysis can provide a precise description of sub-lethal effects on neural function. The chamber has been modified to accommodate L2 larval stages showing applicability for small size nematodes including parasitic species which otherwise are not tractable to this experimental approach. We also combine NeuroChip with optogenetics for targeted interrogation of the function of the neural circuit. NeuroChip thus adds a new tool for exploitation of C. elegans and has applications in neurogenetics, drug discovery and neurotoxicology.

Velocity effect on aptamer-based circulating tumor cell isolation in microfluidic devices.

Science.gov (United States)

Wan, Yuan; Tan, Jifu; Asghar, Waseem; Kim, Young-tae; Liu, Yaling; Iqbal, Samir M

2011-12-01

The isolation and detection of rare circulating tumor cells (CTCs) has been one of the focuses of intense research recently. In a microfluidic device, a number of factors can influence the enrichment capability of surface-bound probe molecules. This article analyzes the important factor of flow velocity in a microfluidic channel. The competition of surface-grafted anti-EGFR aptamers to bind the overexpressed EGFR on cell membranes against the drag force from the fluid flow is an important efficiency determining factor. The flow rate variations are applied both in experiments and in simulation models to study their effects on CTC capture efficiency. A mixture of mononuclear cells and human Glioblastoma cells is used to isolate cancer cells from the cellular flow. The results show interdependence between the adhesion probability, isolation efficiency, and flow rate. This work can help in designing flow-through lab-on-chip devices that use surface-bound probe affinities against overexpressed biomarkers for cell isolation. This work demonstrates that microfluidic based approaches have strong potential applications in CTC detection and isolation. © 2011 American Chemical Society

A microfluidic device with pillars

DEFF Research Database (Denmark)

2014-01-01

The invention provides a microfluidic device for mixing liquid reagents, the device comprises, a chip forming at least one reaction chamber between a bottom and a top and extending between an inlet and an outlet. To enable manufacturing from less rigid materials, the device comprises pillars...

Microfluidic Organ-on-a-Chip Models of Human IntestineSummary

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Amir Bein

Full Text Available Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology and pathophysiology. In this article, we review this field and describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability to analyze contributions of individual cellular, chemical, and physical control parameters one-at-a-time; to coculture human intestinal cells with commensal microbiome for extended times; and to create human-relevant disease models. We also discuss potential future applications of human Intestine Chips, including how they might be used for drug development and personalized medicine. Keywords: Organs-on-Chips, Gut-on-a-Chip, Intestine-on-a-Chip, Microfluidic

Microfluidics for medical applications

NARCIS (Netherlands)

van den Berg, Albert; van den Berg, A.; Segerink, L.I.; Segerink, Loes Irene; Unknown, [Unknown

2015-01-01

Lab-on-a-chip devices for point of care diagnostics have been present in clinics for several years now. Alongside their continual development, research is underway to bring the organs and tissue on-a-chip to the patient, amongst other medical applications of microfluidics. This book provides the

Vertically Aligned Carbon Nanotube Array (VANTA Biosensor for MEMS Lab-on-a-Chip

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Luke JOSEPH

2009-10-01

Full Text Available We describe the fabrication, functionalization and characterization of vertically aligned carbon nanotube arrays (VANTAs for biological sensor applications. This structure is created using a standard MEMS process and chemical vapor deposition (CVD multi-walled carbon nanotube (MWNT post-processing. The device is well suited for full integration into microfluidic lab-on-a-chip solutions. Included is a spectroscopic characterization of the galvanostatic impedance of the device, as well as scanning electron microscopy (SEM images of the pre- and post- functionalized device. Interferometric 3D profiling and X-ray spectroscopy were also used to check process assumptions. The work presented validates that this approach is an ideal candidate for low-cost, high-throughput manufacturing of biochemical sensors. Unlike previously published work [1, 2] using SWNT, the use of MWNT arrays allows functionalization over the entirety of the nanotubes. This approach maintains low baseline impedance and increases the surface area leveraging inherent benefits of the VANTA.

Design and Modelling of a Microfluidic Electro-Lysis Device with Controlling Plates

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Jenkins, A.; Chen, C. P.; Spearing, S.; Monaco, L. A.; Steele, A.; Flores, G.

2006-04-01

Many Lab-on-Chip applications require sample pre-treatment systems. Using electric fields to perform cell lysis in bio-MEMS systems has provided a powerful tool which can be integrated into Lab-on-a- Chip platforms. The major design considerations for electro-lysis devices include optimal geometry and placement of micro-electrodes, cell concentration, flow rates, optimal electric field (e.g. pulsed DC vs. AC), etc. To avoid electrolysis of the flowing solution at the exposed electrode surfaces, magnitudes and the applied voltages and duration of the DC pulse, or the AC frequency of the AC, have to be optimized for a given configuration. Using simulation tools for calculation of electric fields has proved very useful, for exploring alternative configurations and operating conditions for achieving electro cell-lysis. To alleviate the problem associated with low electric fields within the microfluidics channel and the high voltage demand on the contact electrode strips, two ''control plates'' are added to the microfluidics configuration. The principle of placing the two controlling plate-electrodes is based on the electric fields generated by a combined insulator/dielectric (glass/water) media. Surface charges are established at the insulator/dielectric interface. This paper discusses the effects of this interface charge on the modification of the electric field of the flowing liquid/cell solution.

Improving "lab-on-a-chip" techniques using biomedical nanotechnology: a review.

Science.gov (United States)

Gorjikhah, Fatemeh; Davaran, Soodabeh; Salehi, Roya; Bakhtiari, Mohsen; Hasanzadeh, Arash; Panahi, Yunes; Emamverdy, Masumeh; Akbarzadeh, Abolfazl

2016-11-01

Nanotechnology and its applications in biomedical sciences principally in molecular nanodiagnostics are known as nanomolecular diagnostics, which provides new options for clinical nanodiagnostic techniques. Molecular nanodiagnostics are a critical role in the development of personalized medicine, which features point-of care performance of diagnostic procedure. This can to check patients at point-of-care facilities or in remote or resource-poor locations, therefore reducing checking time from days to minutes. In this review, applications of nanotechnology suited to biomedicine are discussed in two main class: biomedical applications for use inside (such as drugs, diagnostic techniques, prostheses, and implants) and outside the body (such as "lab-on-a-chip" techniques). A lab-on-a-chip (LOC) is a tool that incorporates numerous laboratory tasks onto a small device, usually only millimeters or centimeters in size. Finally, are discussed the applications of biomedical nanotechnology in improving "lab-on-a-chip" techniques.

Interfacing Lab-on-a-Chip Embryo Technology with High-Definition Imaging Cytometry.

Science.gov (United States)

Zhu, Feng; Hall, Christopher J; Crosier, Philip S; Wlodkowic, Donald

2015-08-01

To spearhead deployment of zebrafish embryo biotests in large-scale drug discovery studies, automated platforms are needed to integrate embryo in-test positioning and immobilization (suitable for high-content imaging) with fluidic modules for continuous drug and medium delivery under microperfusion to developing embryos. In this work, we present an innovative design of a high-throughput three-dimensional (3D) microfluidic chip-based device for automated immobilization and culture and time-lapse imaging of developing zebrafish embryos under continuous microperfusion. The 3D Lab-on-a-Chip array was fabricated in poly(methyl methacrylate) (PMMA) transparent thermoplastic using infrared laser micromachining, while the off-chip interfaces were fabricated using additive manufacturing processes (fused deposition modelling and stereolithography). The system's design facilitated rapid loading and immobilization of a large number of embryos in predefined clusters of traps during continuous microperfusion of drugs/toxins. It was conceptually designed to seamlessly interface with both upright and inverted fluorescent imaging systems and also to directly interface with conventional microtiter plate readers that accept 96-well plates. Compared with the conventional Petri dish assays, the chip-based bioassay was much more convenient and efficient as only small amounts of drug solutions were required for the whole perfusion system running continuously over 72 h. Embryos were spatially separated in the traps that assisted tracing single embryos, preventing interembryo contamination and improving imaging accessibility.

Materials for microfluidic chip fabrication.

Science.gov (United States)

Ren, Kangning; Zhou, Jianhua; Wu, Hongkai

2013-11-19

Through manipulating fluids using microfabricated channel and chamber structures, microfluidics is a powerful tool to realize high sensitive, high speed, high throughput, and low cost analysis. In addition, the method can establish a well-controlled microenivroment for manipulating fluids and particles. It also has rapid growing implementations in both sophisticated chemical/biological analysis and low-cost point-of-care assays. Some unique phenomena emerge at the micrometer scale. For example, reactions are completed in a shorter amount of time as the travel distances of mass and heat are relatively small; the flows are usually laminar; and the capillary effect becomes dominant owing to large surface-to-volume ratios. In the meantime, the surface properties of the device material are greatly amplified, which can lead to either unique functions or problems that we would not encounter at the macroscale. Also, each material inherently corresponds with specific microfabrication strategies and certain native properties of the device. Therefore, the material for making the device plays a dominating role in microfluidic technologies. In this Account, we address the evolution of materials used for fabricating microfluidic chips, and discuss the application-oriented pros and cons of different materials. This Account generally follows the order of the materials introduced to microfluidics. Glass and silicon, the first generation microfluidic device materials, are perfect for capillary electrophoresis and solvent-involved applications but expensive for microfabriaction. Elastomers enable low-cost rapid prototyping and high density integration of valves on chip, allowing complicated and parallel fluid manipulation and in-channel cell culture. Plastics, as competitive alternatives to elastomers, are also rapid and inexpensive to microfabricate. Their broad variety provides flexible choices for different needs. For example, some thermosets support in-situ fabrication of

Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

Science.gov (United States)

Luka, George; Ahmadi, Ali; Najjaran, Homayoun; Alocilja, Evangelyn; DeRosa, Maria; Wolthers, Kirsten; Malki, Ahmed; Aziz, Hassan; Althani, Asmaa; Hoorfar, Mina

2015-01-01

A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter), increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture. PMID:26633409

Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

Directory of Open Access Journals (Sweden)

George Luka

2015-12-01

Full Text Available A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter, increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture.

Three-dimensional ordered titanium dioxide-zirconium dioxide film-based microfluidic device for efficient on-chip phosphopeptide enrichment.

Science.gov (United States)

Zhao, De; He, Zhongyuan; Wang, Gang; Wang, Hongzhi; Zhang, Qinghong; Li, Yaogang

2016-09-15

Microfluidic technology plays a significant role in separating biomolecules, because of its miniaturization, integration, and automation. Introducing micro/nanostructured functional materials can improve the properties of microfluidic devices, and extend their application. Inverse opal has a three-dimensional ordered net-like structure. It possesses a large surface area and exhibits good mass transport, making it a good candidate for bio-separation. This study exploits inverse opal titanium dioxide-zirconium dioxide films for on-chip phosphopeptide enrichment. Titanium dioxide-zirconium dioxide inverse opal film-based microfluidic devices were constructed from templates of 270-, 340-, and 370-nm-diameter poly(methylmethacrylate) spheres. The phosphopeptide enrichments of these devices were determined by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The device constructed from the 270-nm-diameter sphere template exhibited good comprehensive phosphopeptide enrichment, and was the best among these three devices. Because the size of opal template used in construction was the smallest, the inverse opal film therefore had the smallest pore sizes and the largest surface area. Enrichment by this device was also better than those of similar devices based on nanoparticle films and single component films. The titanium dioxide-zirconium dioxide inverse opal film-based device provides a promising approach for the efficient separation of various biomolecules. Copyright © 2016 Elsevier Inc. All rights reserved.

BioMEMS and Lab-on-a-Chip Course Education at West Virginia University

Directory of Open Access Journals (Sweden)

Yuxin Liu

2011-01-01

Full Text Available With the rapid growth of Biological/Biomedical MicroElectroMechanical Systems (BioMEMS and microfluidic-based lab-on-a-chip (LOC technology to biological and biomedical research and applications, demands for educated and trained researchers and technicians in these fields are rapidly expanding. Universities are expected to develop educational plans to address these specialized needs in BioMEMS, microfluidic and LOC science and technology. A course entitled BioMEMS and Lab-on-a-Chip was taught recently at the senior undergraduate and graduate levels in the Department of Computer Science and Electrical Engineering at West Virginia University (WVU. The course focused on the basic principles and applications of BioMEMS and LOC technology to the areas of biomedicine, biology, and biotechnology. The course was well received and the enrolled students had diverse backgrounds in electrical engineering, material science, biology, mechanical engineering, and chemistry. Student feedback and a review of the course evaluations indicated that the course was effective in achieving its objectives. Student presentations at the end of the course were a highlight and a valuable experience for all involved. The course proved successful and will continue to be offered regularly. This paper provides an overview of the course as well as some development and future improvements.

Rotational microfluidic motor for on-chip microcentrifugation

Science.gov (United States)

Shilton, Richie J.; Glass, Nick R.; Chan, Peggy; Yeo, Leslie Y.; Friend, James R.

2011-06-01

We report on the design of a surface acoustic wave (SAW) driven fluid-coupled micromotor which runs at high rotational velocities. A pair of opposing SAWs generated on a lithium niobate substrate are each obliquely passed into either side of a fluid drop to drive rotation of the fluid, and the thin circular disk set on the drop. Using water for the drop, a 5 mm diameter disk was driven with rotation speeds and start-up torques up to 2250 rpm and 60 nN m, respectively. Most importantly for lab-on-a-chip applications, radial accelerations of 172 m/s2 was obtained, presenting possibilities for microcentrifugation, flow sequencing, assays, and cell culturing in truly microscale lab-on-a-chip devices.

Microfluidic redox battery.

Science.gov (United States)

Lee, Jin Wook; Goulet, Marc-Antoni; Kjeang, Erik

2013-07-07

A miniaturized microfluidic battery is proposed, which is the first membraneless redox battery demonstrated to date. This unique concept capitalizes on dual-pass flow-through porous electrodes combined with stratified, co-laminar flow to generate electrical power on-chip. The fluidic design is symmetric to allow for both charging and discharging operations in forward, reverse, and recirculation modes. The proof-of-concept device fabricated using low-cost materials integrated in a microfluidic chip is shown to produce competitive power levels when operated on a vanadium redox electrolyte. A complete charge/discharge cycle is performed to demonstrate its operation as a rechargeable battery, which is an important step towards providing sustainable power to lab-on-a-chip and microelectronic applications.

A microfabricated microfluidic bioMEMS device to model human brain aneurisms: the aneurysm-on-a-chip

Science.gov (United States)

Reece, Lisa M.; Khor, Jian Wei; Thakur, Raviraj; Amin, Ahmed; Wereley, Steven T.; Leary, James F.

2015-03-01

Aneurysms are pockets of blood that collect outside blood vessel walls forming dilatations and leaving arterial walls very prone to rupture. There is little information concerning the causes of intracranial aneurysm formation, growth, and rupture. Current treatments include: (1) clipping, and (2) coil embolization, including stent-assisted coiling. Further, the evolution of any aneurysm is assumed to be caused by the remodeling of the affected blood vessel's material constituents (tunica intima, tunica media, or tunica adventitia). Velocity, pressure, and wall shear stresses aid in the disease development of aneurysmal growth, while the shear force mechanisms effecting wound closure are elusive. To study aneurysm pathogenesis, a lab-on-a-chip device is the key to discovering the underlying mechanisms of these lesions. A two-dimensional microfluidic model, the Aneurysm-on-a-Chip™ (AOC), was the logical answer to study particle flow within an aneurysm "sac". The AOC apparatus can track particles/cells when it is coupled to particle image velocimetry software (PIV) package. The AOC fluid flow was visualized using standard microscopy techniques with commercial microparticles and human aortic smooth muscle cells (HASMC). Images were taken during fluid flow experiments and PIV was utilized to monitor the flow of particles within the "sac" region, as well as particles entering and exiting the device. Quiver plots were generated from fluid flow experiments using standard 7 μm latex particles and fixed HASMC in PBS. PIV analysis shows that the particles flowed nicely from input to output. Wall shear stress provided evidence that there was some back flow at the edges of the "sac" - an indicator of aneurysm development in human patients.

Lab-on-a-Chip Instrument Development for Titan Exploration

Science.gov (United States)

Willis, P. A.; Greer, F.; Fisher, A.; Hodyss, R. P.; Grunthaner, F.; Jiao, H.; Mair, D.; Harrison, J.

2009-12-01

This contribution will describe the initial stages of a new ASTID-funded research program initiated in Fall 2009 aimed at lab-on-a-chip system development for astrobiological investigations on Titan. This technology development builds off related work at JPL and Berkeley [1-3] on the ultrasensitive compositional and chiral analysis of amino acids on Mars in order to search for signatures of past or present life. The Mars-focused instrument system utilizes a microcapillary electrophoresis (μCE) system integrated with on-chip perfluoropolyether (PFPE) membrane valves and pumps for automated liquid sample handling, on-chip derivitization of samples with fluorescent tags, dilution, and mixing with standards for data calibration. It utilizes a four-layer wafer stack design with CE channels patterned in glass, along with a PFPE membrane, a pneumatic manifold layer, and a fluidic bus layer. Three pneumatically driven on-chip diaphragm valves placed in series are used to peristaltically pump reagents, buffers, and samples to and from capillary electrophoresis electrode well positions. Electrophoretic separation occurs in the all-glass channels near the base of the structure. The Titan specific lab-on-a-chip system under development here focuses its attention on the unique organic chemistry of Titan. In order to chromatographically separate mixtures of neutral organics such as polycyclic aromatic hydrocarbons (PAHs), the Titan-specific microfluidic platform utilizes the related technique of microcapillary electrochromatography (μCEC). This technique differs from conventional μCE in that microchannels are filled with a porous stationary phase that presents surfaces upon which analyte species can adsorb/desorb. It is this additional surface interaction that enables separations of species critical to the understanding of the astrobiological potential of Titan that are not readily separated by the μCE technique. We have developed two different approaches for the integration

Disposable world-to-chip interface for digital microfluidics

Science.gov (United States)

Van Dam, R. Michael; Shah, Gaurav; Keng, Pei-Yuin

2017-05-16

The present disclosure sets forth incorporating microfluidic chips interfaces for use with digital microfluidic processes. Methods and devices according to the present disclosure utilize compact, integrated platforms that interface with a chip upstream and downstream of the reaction, as well as between intermediate reaction steps if needed. In some embodiments these interfaces are automated, including automation of a multiple reagent process. Various reagent delivery systems and methods are also disclosed.

Fuel cell-powered microfluidic platform for lab-on-a-chip applications: Integration into an autonomous amperometric sensing device.

Science.gov (United States)

Esquivel, J P; Colomer-Farrarons, J; Castellarnau, M; Salleras, M; del Campo, F J; Samitier, J; Miribel-Català, P; Sabaté, N

2012-11-07

The present paper reports for the first time the integration of a microfluidic system, electronics modules, amperometric sensor and display, all powered by a single micro direct methanol fuel cell. In addition to activating the electronic circuitry, the integrated power source also acts as a tuneable micropump. The electronics fulfil several functions. First, they regulate the micro fuel cell output power, which off-gas controls the flow rate of different solutions toward an electrochemical sensor through microfluidic channels. Secondly, as the fuel cell powers a three-electrode electrochemical cell, the electronics compare the working electrode output signal with a set reference value. Thirdly, if the concentration measured by the sensor exceeds this threshold value, the electronics switch on an integrated organic display. This integrated approach pushes forward the development of truly autonomous point-of-care devices relying on electrochemical detection.

Direct current insulator based dielectrophoresis (DC-iDEP) microfluidic chip for blood plasma separation

OpenAIRE

Mohammadi, Mahdi

2015-01-01

Lab-on-a-Chip (LOC) integrated microfluidics has been a powerful tool for new developments in analytical chemistry. These microfluidic systems enable the miniaturization, integration and automation of complex biochemical assays through the reduction of reagent use and enabling portability.Cell and particle separation in microfluidic systems has recently gained significant attention in many sample preparations for clinical procedures. Direct-current insulator-based dielectrophoresis (DC-iDEP) ...

“Connecting worlds – a view on microfluidics for a wider application”

DEFF Research Database (Denmark)

Fernandes, Ana C.; Gernaey, Krist V.; Krühne, Ulrich

2018-01-01

acceptance and more widespread use, are introduced. A brief review of the main materials and fabrication strategies used in these fields, is also presented. Finally, a step-wise guide towards the development of microfluidic systems is introduced with special focus on the integration of sensors...... of miniaturizing industrial production plants, thereby increasing their automation and operational safety at low cost; (2) being able to identify rare diseases by running bioanalytics directly on the patient’s skin; (3) allowing health diagnostics in point-of-care sites through cheap lab-on-a-chip devices. However...... and biotechnology fields, focusing mainly on the specialization on a single target of most microfluidic devices and offering a perspective on the alternate, multi-use, “plug and play” approach. Increasing the flexibility of microfluidic platforms, by increasing their compatibility with different substrates...

Invited Article: Terahertz microfluidic chips sensitivity-enhanced with a few arrays of meta-atoms

Directory of Open Access Journals (Sweden)

Kazunori Serita

2018-05-01

Full Text Available We present a nonlinear optical crystal (NLOC-based terahertz (THz microfluidic chip with a few arrays of split ring resonators (SRRs for ultra-trace and quantitative measurements of liquid solutions. The proposed chip operates on the basis of near-field coupling between the SRRs and a local emission of point like THz source that is generated in the process of optical rectification in NLOCs on a sub-wavelength scale. The liquid solutions flowing inside the microchannel modify the resonance frequency and peak attenuation in the THz transmission spectra. In contrast to conventional bio-sensing with far/near-field THz waves, our technique can be expected to compactify the chip design as well as realize high sensitive near-field measurement of liquid solutions without any high-power optical/THz source, near-field probes, and prisms. Using this chip, we have succeeded in observing the 31.8 fmol of ion concentration in actual amount of 318 pl water solutions from the shift of the resonance frequency. The technique opens the door to microanalysis of biological samples with THz waves and accelerates development of THz lab-on-chip devices.

Invited Article: Terahertz microfluidic chips sensitivity-enhanced with a few arrays of meta-atoms

Science.gov (United States)

Serita, Kazunori; Matsuda, Eiki; Okada, Kosuke; Murakami, Hironaru; Kawayama, Iwao; Tonouchi, Masayoshi

2018-05-01

We present a nonlinear optical crystal (NLOC)-based terahertz (THz) microfluidic chip with a few arrays of split ring resonators (SRRs) for ultra-trace and quantitative measurements of liquid solutions. The proposed chip operates on the basis of near-field coupling between the SRRs and a local emission of point like THz source that is generated in the process of optical rectification in NLOCs on a sub-wavelength scale. The liquid solutions flowing inside the microchannel modify the resonance frequency and peak attenuation in the THz transmission spectra. In contrast to conventional bio-sensing with far/near-field THz waves, our technique can be expected to compactify the chip design as well as realize high sensitive near-field measurement of liquid solutions without any high-power optical/THz source, near-field probes, and prisms. Using this chip, we have succeeded in observing the 31.8 fmol of ion concentration in actual amount of 318 pl water solutions from the shift of the resonance frequency. The technique opens the door to microanalysis of biological samples with THz waves and accelerates development of THz lab-on-chip devices.

A Lab-on-Chip Design for Miniature Autonomous Bio-Chemoprospecting Planetary Rovers

Science.gov (United States)

Santoli, S.

The performance of the so-called ` Lab-on-Chip ' devices, featuring micrometre size components and employed at present for carrying out in a very fast and economic way the extremely high number of sequence determinations required in genomic analyses, can be largely improved as to further size reduction, decrease of power consumption and reaction efficiency through development of nanofluidics and of nano-to-micro inte- grated systems. As is shown, such new technologies would lead to robotic, fully autonomous, microwatt consumption and complete ` laboratory on a chip ' units for accurate, fast and cost-effective astrobiological and planetary exploration missions. The theory and the manufacturing technologies for the ` active chip ' of a miniature bio/chemoprospecting planetary rover working on micro- and nanofluidics are investigated. The chip would include micro- and nanoreactors, integrated MEMS (MicroElectroMechanical System) components, nanoelectronics and an intracavity nanolaser for highly accurate and fast chemical analysis as an application of such recently introduced solid state devices. Nano-reactors would be able to strongly speed up reaction kinetics as a result of increased frequency of reactive collisions. The reaction dynamics may also be altered with respect to standard macroscopic reactors. A built-in miniature telemetering unit would connect a network of other similar rovers and a central, ground-based or orbiting control unit for data collection and transmission to an Earth-based unit through a powerful antenna. The development of the ` Lab-on-Chip ' concept for space applications would affect the economy of space exploration missions, as the rover's ` Lab-on-Chip ' development would link space missions with the ever growing terrestrial market and business concerning such devices, largely employed in modern genomics and bioinformatics, so that it would allow the recoupment of space mission costs.

Automated, Miniaturized and Integrated Quality Control-on-Chip (QC-on-a-Chip for Advanced Cell Therapy Applications

Directory of Open Access Journals (Sweden)

David eWartmann

2015-09-01

Full Text Available The combination of microfabrication-based technologies with cell biology has laid the foundation for the development of advanced in vitro diagnostic systems capable of evaluating cell cultures under defined, reproducible and standardizable measurement conditions. In the present review we describe recent lab-on-a-chip developments for cell analysis and how these methodologies could improve standard quality control in the field of manufacturing cell-based vaccines for clinical purposes. We highlight in particular the regulatory requirements for advanced cell therapy applications using as an example dendritic cell-based cancer vaccines to describe the tangible advantages of microfluidic devices that overcome most of the challenges associated with automation, miniaturization and integration of cell-based assays. As its main advantage lab-on-a-chip technology allows for precise regulation of culturing conditions, while simultaneously monitoring cell relevant parameters using embedded sensory systems. State-of-the-art lab-on-a-chip platforms for in vitro assessment of cell cultures and their potential future applications for cell therapies and cancer immunotherapy are discussed in the present review.

Automated, Ultra-Sterile Solid Sample Handling and Analysis on a Chip

Science.gov (United States)

Mora, Maria F.; Stockton, Amanda M.; Willis, Peter A.

2013-01-01

There are no existing ultra-sterile lab-on-a-chip systems that can accept solid samples and perform complete chemical analyses without human intervention. The proposed solution is to demonstrate completely automated lab-on-a-chip manipulation of powdered solid samples, followed by on-chip liquid extraction and chemical analysis. This technology utilizes a newly invented glass micro-device for solid manipulation, which mates with existing lab-on-a-chip instrumentation. Devices are fabricated in a Class 10 cleanroom at the JPL MicroDevices Lab, and are plasma-cleaned before and after assembly. Solid samples enter the device through a drilled hole in the top. Existing micro-pumping technology is used to transfer milligrams of powdered sample into an extraction chamber where it is mixed with liquids to extract organic material. Subsequent chemical analysis is performed using portable microchip capillary electrophoresis systems (CE). These instruments have been used for ultra-highly sensitive (parts-per-trillion, pptr) analysis of organic compounds including amines, amino acids, aldehydes, ketones, carboxylic acids, and thiols. Fully autonomous amino acid analyses in liquids were demonstrated; however, to date there have been no reports of completely automated analysis of solid samples on chip. This approach utilizes an existing portable instrument that houses optics, high-voltage power supplies, and solenoids for fully autonomous microfluidic sample processing and CE analysis with laser-induced fluorescence (LIF) detection. Furthermore, the entire system can be sterilized and placed in a cleanroom environment for analyzing samples returned from extraterrestrial targets, if desired. This is an entirely new capability never demonstrated before. The ability to manipulate solid samples, coupled with lab-on-a-chip analysis technology, will enable ultraclean and ultrasensitive end-to-end analysis of samples that is orders of magnitude more sensitive than the ppb goal given

Multi-color fluorescent DNA analysis in an integrated optofluidic lab-on-a-chip

NARCIS (Netherlands)

Dongre, C.; van Weerd, J.; van Weeghel, R.; Martinez-Vazquez, R.; Osellame, R.; Cerullo, G.; Besselink, G.A.J.; van den Vlekkert, H.H.; Hoekstra, Hugo; Pollnau, Markus

Sorting and sizing of DNA molecules within the human genome project has enabled the genetic mapping of various illnesses. By employing tiny lab-on-a-chip devices for such DNA analysis, integrated DNA sequencing and genetic diagnostics have become feasible. However, such diagnostic chips typically

Microfluidic desalination : capacitive deionization on chip for microfluidic sample preparation

NARCIS (Netherlands)

Roelofs, Susan Helena

2015-01-01

The main aim of the work described in this thesis is to implement the desalination technique capacitive deionization (CDI) on a microfluidic chip to improve the reproducibility in the analysis of biological samples for drug development. Secondly, microfluidic CDI allows for the in situ study of ion

Laser subtractive-additive-welding microfabrication for Lab-On-Chip (LOC) applications

Science.gov (United States)

Jonušauskas, Linas; RekštytÄ--, Sima; Buivydas, Ričardas; Butkus, Simas; Paipulas, Domas; Gadonas, Roaldas; Juodkazis, Saulius; Malinauskas, Mangirdas

2017-02-01

An approach employing ultrafast laser hybrid microfabrication combining ablation, 3D nanolithography and welding is proposed for the realization of Lab-On-Chip (LOC) device. The same laser setup is shown to be suitable for fabricating microgrooves in glass slabs, polymerization of fine meshes inside them, and, lastly, sealing the whole chip with cover glass into one monolithic piece. The created micro fluidic device proved its particle sorting function by separating 1 μm and 10 μm polystyrene spheres from a mixture. Next, a lens adapter for a cell phone's camera was manufactured via thermal extrusion 3D printing technique which allowed to achieve sufficient magnification to clearly resolve <10 μm features. All together shows fs-laser microfabrication technology as a flexible and versatile tool for study and manufacturing of Lab-On-Chip devices.

Microfluidics without channels: highly-flexible synthesis on a digital-microfluidic chip for production of diverse PET tracers

Energy Technology Data Exchange (ETDEWEB)

Van Dam, Robert Michael [Univ. of California, Los Angeles, CA (United States)

2010-09-01

Positron emission tomography (PET) imaging is used for fundamental studies of living biological organisms and microbial ecosystems in applications ranging from biofuel production to environmental remediation to the study, diagnosis, and treatment monitoring of human disease. Routine access to PET imaging, to monitor biochemical reactions in living organisms in real time, could accelerate a broad range of research programs of interest to DOE. Using PET requires access to short-lived radioactive-labeled compounds that specifically probe the desired living processes. The overall aims of this project were to develop a miniature liquid-handling technology platform (called “microfluidics”) that increases the availability of diverse PET probes by reducing the cost and complexity of their production. Based on preliminary experiments showing that microfluidic chips can synthesis such compounds, we aimed to advance this technology to improve its robustness, increase its flexibility for a broad range of probes, and increase its user-friendliness. Through the research activities of this project, numerous advances were made; Tools were developed to enable the visualization of radioactive materials within microfluidic chips; Fundamental advances were made in the microfluidic chip architecture and fabrication process to increase its robustness and reliability; The microfluidic chip technology was shown to produce useful quantities of an example PET probes, and methods to further increase the output were successfully pursued; A “universal” chip was developed that could produce multiple types of PET probes, enabling the possibility of “on demand” synthesis of different probes; and Operation of the chip was automated to ensure minimal radiation exposure to the operator Based on the demonstrations of promising technical feasibility and performance, the microfluidic chip technology is currently being commercialized. It is anticipated that costs of microfluidic chips can be

An open-source, programmable pneumatic setup for operation and automated control of single- and multi-layer microfluidic devices

Directory of Open Access Journals (Sweden)

Kara Brower

2018-04-01

Full Text Available Microfluidic technologies have been used across diverse disciplines (e.g. high-throughput biological measurement, fluid physics, laboratory fluid manipulation but widespread adoption has been limited in part due to the lack of openly disseminated resources that enable non-specialist labs to make and operate their own devices. Here, we report the open-source build of a pneumatic setup capable of operating both single and multilayer (Quake-style microfluidic devices with programmable scripting automation. This setup can operate both simple and complex devices with 48 device valve control inputs and 18 sample inputs, with modular design for easy expansion, at a fraction of the cost of similar commercial solutions. We present a detailed step-by-step guide to building the pneumatic instrumentation, as well as instructions for custom device operation using our software, Geppetto, through an easy-to-use GUI for live on-chip valve actuation and a scripting system for experiment automation. We show robust valve actuation with near real-time software feedback and demonstrate use of the setup for high-throughput biochemical measurements on-chip. This open-source setup will enable specialists and novices alike to run microfluidic devices easily in their own laboratories. Keywords: Microfluidics, Pneumatics, Laboratory automation, Biochip, BioMEMs, Biohacking, Fluid handling, Micro total analysis systems (μTAS, Quake-style valves

A 3D Microfluidic Chip for Electrochemical Detection of Hydrolysed Nucleic Bases by a Modified Glassy Carbon Electrode

Directory of Open Access Journals (Sweden)

Jana Vlachova

2015-01-01

Full Text Available Modification of carbon materials, especially graphene-based materials, has wide applications in electrochemical detection such as electrochemical lab-on-chip devices. A glassy carbon electrode (GCE modified with chemically alternated graphene oxide was used as a working electrode (glassy carbon modified by graphene oxide with sulphur containing compounds and Nafion for detection of nucleobases in hydrolysed samples (HCl pH = 2.9, 100 °C, 1 h, neutralization by NaOH. It was found out that modification, especially with trithiocyanuric acid, increased the sensitivity of detection in comparison with pure GCE. All processes were finally implemented in a microfluidic chip formed with a 3D printer by fused deposition modelling technology. As a material for chip fabrication, acrylonitrile butadiene styrene was chosen because of its mechanical and chemical stability. The chip contained the one chamber for the hydrolysis of the nucleic acid and another for the electrochemical detection by the modified GCE. This chamber was fabricated to allow for replacement of the GCE.

A 3D microfluidic chip for electrochemical detection of hydrolysed nucleic bases by a modified glassy carbon electrode.

Science.gov (United States)

Vlachova, Jana; Tmejova, Katerina; Kopel, Pavel; Korabik, Maria; Zitka, Jan; Hynek, David; Kynicky, Jindrich; Adam, Vojtech; Kizek, Rene

2015-01-22

Modification of carbon materials, especially graphene-based materials, has wide applications in electrochemical detection such as electrochemical lab-on-chip devices. A glassy carbon electrode (GCE) modified with chemically alternated graphene oxide was used as a working electrode (glassy carbon modified by graphene oxide with sulphur containing compounds and Nafion) for detection of nucleobases in hydrolysed samples (HCl pH = 2.9, 100 °C, 1 h, neutralization by NaOH). It was found out that modification, especially with trithiocyanuric acid, increased the sensitivity of detection in comparison with pure GCE. All processes were finally implemented in a microfluidic chip formed with a 3D printer by fused deposition modelling technology. As a material for chip fabrication, acrylonitrile butadiene styrene was chosen because of its mechanical and chemical stability. The chip contained the one chamber for the hydrolysis of the nucleic acid and another for the electrochemical detection by the modified GCE. This chamber was fabricated to allow for replacement of the GCE.

A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation.

Science.gov (United States)

Wu, Huei-Wen; Hsiao, Yi-Hsing; Chen, Chih-Chen; Yet, Shaw-Fang; Hsu, Chia-Hsien

2016-07-06

The conventional hanging drop technique is the most widely used method for embryoid body (EB) formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 × 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS) from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 μm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip.

A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation

Directory of Open Access Journals (Sweden)

Huei-Wen Wu

2016-07-01

Full Text Available The conventional hanging drop technique is the most widely used method for embryoid body (EB formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 × 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 μm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip.

Electrostatic charging and control of droplets in microfluidic devices.

Science.gov (United States)

Zhou, Hongbo; Yao, Shuhuai

2013-03-07

Precharged droplets can facilitate manipulation and control of low-volume liquids in droplet-based microfluidics. In this paper, we demonstrate non-contact electrostatic charging of droplets by polarizing a neutral droplet and splitting it into two oppositely charged daughter droplets in a T-junction microchannel. We performed numerical simulation to analyze the non-contact charging process and proposed a new design with a notch at the T-junction in aid of droplet splitting for more efficient charging. We experimentally characterized the induced charge in droplets in microfabricated devices. The experimental results agreed well with the simulation. Finally, we demonstrated highly effective droplet manipulation in a path selection unit appending to the droplet charging. We expect our work could enable precision manipulation of droplets for more complex liquid handling in microfluidics and promote electric-force based manipulation in 'lab-on-a-chip' systems.

3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs.

Science.gov (United States)

Knowlton, Stephanie; Yu, Chu Hsiang; Ersoy, Fulya; Emadi, Sharareh; Khademhosseini, Ali; Tasoglu, Savas

2016-06-20

Three-dimensional (3D) printing offers potential to fabricate high-throughput and low-cost fabrication of microfluidic devices as a promising alternative to traditional techniques which enables efficient design iterations in the development stage. In this study, we demonstrate a single-step fabrication of a 3D transparent microfluidic chip using two alternative techniques: a stereolithography-based desktop 3D printer and a two-step fabrication using an industrial 3D printer based on polyjet technology. This method, compared to conventional fabrication using relatively expensive materials and labor-intensive processes, presents a low-cost, rapid prototyping technique to print functional 3D microfluidic chips. We enhance the capabilities of 3D-printed microfluidic devices by coupling 3D cell encapsulation and spatial patterning within photocrosslinkable gelatin methacryloyl (GelMA). The platform presented here serves as a 3D culture environment for long-term cell culture and growth. Furthermore, we have demonstrated the ability to print complex 3D microfluidic channels to create predictable and controllable fluid flow regimes. Here, we demonstrate the novel use of 3D-printed microfluidic chips as controllable 3D cell culture environments, advancing the applicability of 3D printing to engineering physiological systems for future applications in bioengineering.

Integration of microelectronic chips in microfluidic systems on printed circuit board

International Nuclear Information System (INIS)

Burdallo, I; Jimenez-Jorquera, C; Fernández-Sánchez, C; Baldi, A

2012-01-01

A new scheme for the integration of small semiconductor transducer chips with microfluidic structures on printed circuit board (PCB) is presented. The proposed approach is based on a packaging technique that yields a large and flat area with small and shallow (∼44 µm deep) openings over the chips. The photocurable encapsulant material used, based on a diacrylate bisphenol A polymer, enables irreversible bonding of polydimethylsiloxane microfluidic structures at moderate temperatures (80 °C). This integration scheme enables the insertion of transducer chips in microfluidic systems with a lower added volume than previous schemes. Leakage tests have shown that the bonded structures withstand more than 360 kPa of pressure. A prototype microfluidic system with two detection chips, including one inter-digitated electrode (IDE) chip for conductivity and one ion selective field effect transistor (ISFET) chip for pH, has been implemented and characterized. Good electrical insulation of the chip contacts and silicon edge surfaces from the solution in the microchannels has been achieved. This integration procedure opens the door to the low-cost fabrication of complex analytical microsystems that combine the extraordinary potential of both the microfluidics and silicon microtechnology fields. (paper)

Theoretical microfluidics

DEFF Research Database (Denmark)

Bruus, Henrik

Microfluidics is a young and rapidly expanding scientific discipline, which deals with fluids and solutions in miniaturized systems, the so-called lab-on-a-chip systems. It has applications in chemical engineering, pharmaceutics, biotechnology and medicine. As the lab-on-a-chip systems grow...

Patterned Fibers Embedded Microfluidic Chips Based on PLA and PDMS for Ag Nanoparticle Safety Testing

Directory of Open Access Journals (Sweden)

Yaowen Liu

2016-11-01

Full Text Available A new method to integrate poly-dl-lactide (PLA patterned electrospun fibers with a polydimethylsiloxane (PDMS microfluidic chip was successfully developed via lithography. Hepatocyte behavior under static and dynamic conditions was investigated. Immunohistochemical analyses indicated good hepatocyte survival under the dynamic culture system with effective hepatocyte spheroid formation in the patterned microfluidic chip vs. static culture conditions and tissue culture plate (TCP. In particular, hepatocytes seeded in this microfluidic chip under a flow rate of 10 μL/min could re-establish hepatocyte polarity to support biliary excretion and were able to maintain high levels of albumin and urea secretion over 15 days. Furthermore, the optimized system could produce sensitive and consistent responses to nano-Ag-induced hepatotoxicity during culture. Thus, this microfluidic chip device provides a new means of fabricating complex liver tissue-engineered scaffolds, and may be of considerable utility in the toxicity screening of nanoparticles.

Easy monitoring of velocity fields in microfluidic devices using spatiotemporal image correlation spectroscopy.

Science.gov (United States)

Travagliati, Marco; Girardo, Salvatore; Pisignano, Dario; Beltram, Fabio; Cecchini, Marco

2013-09-03

Spatiotemporal image correlation spectroscopy (STICS) is a simple and powerful technique, well established as a tool to probe protein dynamics in cells. Recently, its potential as a tool to map velocity fields in lab-on-a-chip systems was discussed. However, the lack of studies on its performance has prevented its use for microfluidics applications. Here, we systematically and quantitatively explore STICS microvelocimetry in microfluidic devices. We exploit a simple experimental setup, based on a standard bright-field inverted microscope (no fluorescence required) and a high-fps camera, and apply STICS to map liquid flow in polydimethylsiloxane (PDMS) microchannels. Our data demonstrates optimal 2D velocimetry up to 10 mm/s flow and spatial resolution down to 5 μm.

Microfluidic Devices for Chemical and Biochemical Analysis in Microgravity

Science.gov (United States)

Roman, Gregory T.; Culbertson, Christopher T.; Meyer, Amanda; Ramsey, J. Michael; Gonda, Steven R.

2004-01-01

One often touted benefit of "Lab-on-a-Chip" devices is their potential for use in remote environments. The ultimate remote environment is outer space, and NASA has multiple needs in the area of analytical sensing capability in such an environment. In particular, we are interested in integrating microfluidic devices with NASA bioreactor systems. In such an integrated system, the microfluidic device will serve as a biosensor and be used for both feedback control and for detecting various bioproducts produced by cells cultured in the NASA bioreactors. As a first step in demonstrating the ability of microfluidic devices to operate under the extreme environmental conditions found in outer space, we constructed a portable, battery operated platform for testing under reduced gravity conditions on a NASA KC-135 reduced gravity research aircraft, (AKA "the vomit comet"). The test platform consisted of a microchip, two 0-8kV high voltage power supplies, a high voltage switch, a solid-state diode-pumped green laser, a channel photomultiplier, and an inertial mass measurement unit, all under the control of a laptop computer and powered by 10 D-cell alkaline batteries. Over the course of 4 KC-135 flights, 1817 fast electrophoretic separations of 4 amino acids and/or proteins were performed in a variety of gravitational environments including zero-G, Martian-G, lunar-G, and 2-G. Results from these experiments will be presented and discussed.

Microfluidic device for acoustic cell lysis

Science.gov (United States)

Branch, Darren W.; Cooley, Erika Jane; Smith, Gennifer Tanabe; James, Conrad D.; McClain, Jaime L.

2015-08-04

A microfluidic acoustic-based cell lysing device that can be integrated with on-chip nucleic acid extraction. Using a bulk acoustic wave (BAW) transducer array, acoustic waves can be coupled into microfluidic cartridges resulting in the lysis of cells contained therein by localized acoustic pressure. Cellular materials can then be extracted from the lysed cells. For example, nucleic acids can be extracted from the lysate using silica-based sol-gel filled microchannels, nucleic acid binding magnetic beads, or Nafion-coated electrodes. Integration of cell lysis and nucleic acid extraction on-chip enables a small, portable system that allows for rapid analysis in the field.

Inkjet printing of UV-curable adhesive and dielectric inks for microfluidic devices.

Science.gov (United States)

Hamad, E M; Bilatto, S E R; Adly, N Y; Correa, D S; Wolfrum, B; Schöning, M J; Offenhäusser, A; Yakushenko, A

2016-01-07

Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing.

Microfluidic "Pouch" Chips for Immunoassays and Nucleic Acid Amplification Tests.

Science.gov (United States)

Mauk, Michael G; Liu, Changchun; Qiu, Xianbo; Chen, Dafeng; Song, Jinzhao; Bau, Haim H

2017-01-01

Microfluidic cassettes ("chips") for processing and analysis of clinical specimens and other sample types facilitate point-of-care (POC) immunoassays and nucleic acid based amplification tests. These single-use test chips can be self-contained and made amenable to autonomous operation-reducing or eliminating supporting instrumentation-by incorporating laminated, pliable "pouch" and membrane structures for fluid storage, pumping, mixing, and flow control. Materials and methods for integrating flexible pouch compartments and diaphragm valves into hard plastic (e.g., acrylic and polycarbonate) microfluidic "chips" for reagent storage, fluid actuation, and flow control are described. We review several versions of these pouch chips for immunoassay and nucleic acid amplification tests, and describe related fabrication techniques. These protocols thus offer a "toolbox" of methods for storage, pumping, and flow control functions in microfluidic devices.

Macromolecular Crystal Growth by Means of Microfluidics

Science.gov (United States)

vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

2002-01-01

We have performed a feasibility study in which we show that chip-based, microfluidic (LabChip(TM)) technology is suitable for protein crystal growth. This technology allows for accurate and reliable dispensing and mixing of very small volumes while minimizing bubble formation in the crystallization mixture. The amount of (protein) solution remaining after completion of an experiment is minimal, which makes this technique efficient and attractive for use with proteins, which are difficult or expensive to obtain. The nature of LabChip(TM) technology renders it highly amenable to automation. Protein crystals obtained in our initial feasibility studies were of excellent quality as determined by X-ray diffraction. Subsequent to the feasibility study, we designed and produced the first LabChip(TM) device specifically for protein crystallization in batch mode. It can reliably dispense and mix from a range of solution constituents into two independent growth wells. We are currently testing this design to prove its efficacy for protein crystallization optimization experiments. In the near future we will expand our design to incorporate up to 10 growth wells per LabChip(TM) device. Upon completion, additional crystallization techniques such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility for the International Space Station as well as on the ground.

Implementation of Microfluidic Chip Electrophoresis for the Detection of B-cell Clonality

Directory of Open Access Journals (Sweden)

Vazan M

2016-04-01

Full Text Available Introduction: A clonal population of B-cells is defined as those cells arising from the mitotic division of a single somatic cell with the same rearrangement of immunoglobulin genes. This gives rise to DNA markers for each individual lymphoid cell and its progenies and enables us to study clonality in different B-cell malignancies using multiplex polymerase chain reaction - PCR. The BIOMED-2 protocol has been implemented for clonality detection in lymphoproliferative diseases and exploits multiplex PCR reaction, subsequently analyzed by heteroduplex analysis (HDA using polyacrylamide gel electrophoresis (PAGE. With the advent of miniaturization and automation of molecular biology methods, lab-on-chip technologies were developed and replace partially the conventional approaches. We tested device for microfluidic chip, which is used for B-cells clonality analysis, using a PCR reaction for three subregions called frameworks (FR of the immunoglobulin heavy locus (IGH gene.

Material Biocompatibility for PCR Microfluidic Chips

KAUST Repository

Kodzius, Rimantas

2010-04-23

As part of the current miniaturization trend, biological reactions and processes are being adapted to microfluidics devices. PCR is the primary method employed in DNA amplification, its miniaturization is central to efforts to develop portable devices for diagnostics and testing purposes. A problem is the PCR-inhibitory effect due to interaction between PCR reagents and the surrounding environment, which effect is increased in high-surface-are-to-volume ration microfluidics. In this study, we evaluated the biocompatibility of various common materials employed in the fabrication of microfluidic chips, including silicon, several kinds of silicon oxide, glasses, plastics, wax, and adhesives. Two-temperature PCR was performed with these materials to determine their PCR-inhibitory effect. In most of the cases, addition of bovine serum albumin effectively improved the reaction yield. We also studied the individual PCR components from the standpoint of adsorption. Most of the materials did not inhibit the DNA, whereas they did show noticeable interaction with the DNA polymerase. Our test, instead of using microfluidic devices, can be easily conducted in common PCR tubes using a standard bench thermocycler. Our data supports an overview of the means by which the materials most bio-friendly to microfluidics can be selected.

Material Biocompatibility for PCR Microfluidic Chips

KAUST Repository

Kodzius, Rimantas; Chang, Donald Choy; Gong, Xiuqing; Wen, Weijia; Wu, Jinbo; Xiao, Kang; Yi, Xin

2010-01-01

As part of the current miniaturization trend, biological reactions and processes are being adapted to microfluidics devices. PCR is the primary method employed in DNA amplification, its miniaturization is central to efforts to develop portable devices for diagnostics and testing purposes. A problem is the PCR-inhibitory effect due to interaction between PCR reagents and the surrounding environment, which effect is increased in high-surface-are-to-volume ration microfluidics. In this study, we evaluated the biocompatibility of various common materials employed in the fabrication of microfluidic chips, including silicon, several kinds of silicon oxide, glasses, plastics, wax, and adhesives. Two-temperature PCR was performed with these materials to determine their PCR-inhibitory effect. In most of the cases, addition of bovine serum albumin effectively improved the reaction yield. We also studied the individual PCR components from the standpoint of adsorption. Most of the materials did not inhibit the DNA, whereas they did show noticeable interaction with the DNA polymerase. Our test, instead of using microfluidic devices, can be easily conducted in common PCR tubes using a standard bench thermocycler. Our data supports an overview of the means by which the materials most bio-friendly to microfluidics can be selected.

Desktop aligner for fabrication of multilayer microfluidic devices.

Science.gov (United States)

Li, Xiang; Yu, Zeta Tak For; Geraldo, Dalton; Weng, Shinuo; Alve, Nitesh; Dun, Wu; Kini, Akshay; Patel, Karan; Shu, Roberto; Zhang, Feng; Li, Gang; Jin, Qinghui; Fu, Jianping

2015-07-01

Multilayer assembly is a commonly used technique to construct multilayer polydimethylsiloxane (PDMS)-based microfluidic devices with complex 3D architecture and connectivity for large-scale microfluidic integration. Accurate alignment of structure features on different PDMS layers before their permanent bonding is critical in determining the yield and quality of assembled multilayer microfluidic devices. Herein, we report a custom-built desktop aligner capable of both local and global alignments of PDMS layers covering a broad size range. Two digital microscopes were incorporated into the aligner design to allow accurate global alignment of PDMS structures up to 4 in. in diameter. Both local and global alignment accuracies of the desktop aligner were determined to be about 20 μm cm(-1). To demonstrate its utility for fabrication of integrated multilayer PDMS microfluidic devices, we applied the desktop aligner to achieve accurate alignment of different functional PDMS layers in multilayer microfluidics including an organs-on-chips device as well as a microfluidic device integrated with vertical passages connecting channels located in different PDMS layers. Owing to its convenient operation, high accuracy, low cost, light weight, and portability, the desktop aligner is useful for microfluidic researchers to achieve rapid and accurate alignment for generating multilayer PDMS microfluidic devices.

Fabrication of microfluidic architectures for optimal flow rate and concentration measurement for lab on chip application

Science.gov (United States)

Adam, Tijjani; Hashim, U.

2017-03-01

Optimum flow in micro channel for sensing purpose is challenging. In this study, The optimizations of the fluid sample flows are made through the design and characterization of the novel microfluidics' architectures to achieve the optimal flow rate in the micro channels. The biocompatibility of the Polydimetylsiloxane (Sylgard 184 silicon elastomer) polymer used to fabricate the device offers avenue for the device to be implemented as the universal fluidic delivery system for bio-molecules sensing in various bio-medical applications. The study uses the following methodological approaches, designing a novel microfluidics' architectures by integrating the devices on a single 4 inches silicon substrate, fabricating the designed microfluidic devices using low-cost solution soft lithography technique, characterizing and validating the flow throughput of urine samples in the micro channels by generating pressure gradients through the devices' inlets. The characterization on the urine samples flow in the micro channels have witnessed the constant flow throughout the devices.

Wax-bonding 3D microfluidic chips

KAUST Repository

Gong, Xiuqing; Yi, Xin; Xiao, Kang; Li, Shunbo; Kodzius, Rimantas; Qin, Jianhua; Wen, Weijia

2013-01-01

We report a simple, low-cost and detachable microfluidic chip incorporating easily accessible paper, glass slides or other polymer films as the chip materials along with adhesive wax as the recycling bonding material. We use a laser to cut through the paper or film to form patterns and then sandwich the paper and film between glass sheets or polymer membranes . The hot-melt adhesive wax can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate (PMMA) film, glass sheets, or metal plate. The bonding process is reversible and the wax is reusable through a melting and cooling process. With this process, a three-dimensional (3D) microfluidic chip is achievable by vacuating and venting the chip in a hot-water bath. To study the biocompatibility and applicability of the wax-based microfluidic chip, we tested the PCR compatibility with the chip materials first. Then we applied the wax-paper based microfluidic chip to HeLa cell electroporation (EP ). Subsequently, a prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check the sealing ability and the durability of the chip, green fluorescence protein (GFP) recombinant Escherichia coli (E. coli) bacteria were cultured, with which the chemotaxis of E. coli was studied in order to determine the influence of antibiotic ciprofloxacin concentration on the E. coli migration.

Wax-bonding 3D microfluidic chips

KAUST Repository

Gong, Xiuqing

2013-10-10

We report a simple, low-cost and detachable microfluidic chip incorporating easily accessible paper, glass slides or other polymer films as the chip materials along with adhesive wax as the recycling bonding material. We use a laser to cut through the paper or film to form patterns and then sandwich the paper and film between glass sheets or polymer membranes . The hot-melt adhesive wax can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate (PMMA) film, glass sheets, or metal plate. The bonding process is reversible and the wax is reusable through a melting and cooling process. With this process, a three-dimensional (3D) microfluidic chip is achievable by vacuating and venting the chip in a hot-water bath. To study the biocompatibility and applicability of the wax-based microfluidic chip, we tested the PCR compatibility with the chip materials first. Then we applied the wax-paper based microfluidic chip to HeLa cell electroporation (EP ). Subsequently, a prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check the sealing ability and the durability of the chip, green fluorescence protein (GFP) recombinant Escherichia coli (E. coli) bacteria were cultured, with which the chemotaxis of E. coli was studied in order to determine the influence of antibiotic ciprofloxacin concentration on the E. coli migration.

Thin film metal sensors in fusion bonded glass chips for high-pressure microfluidics

International Nuclear Information System (INIS)

Andersson, Martin; Ek, Johan; Hedman, Ludvig; Johansson, Fredrik; Sehlstedt, Viktor; Stocklassa, Jesper; Snögren, Pär; Pettersson, Victor; Larsson, Jonas; Vizuete, Olivier; Hjort, Klas; Klintberg, Lena

2017-01-01

High-pressure microfluidics offers fast analyses of thermodynamic parameters for compressed process solvents. However, microfluidic platforms handling highly compressible supercritical CO 2 are difficult to control, and on-chip sensing would offer added control of the devices. Therefore, there is a need to integrate sensors into highly pressure tolerant glass chips. In this paper, thin film Pt sensors were embedded in shallow etched trenches in a glass wafer that was bonded with another glass wafer having microfluidic channels. The devices having sensors integrated into the flow channels sustained pressures up to 220 bar, typical for the operation of supercritical CO 2 . No leakage from the devices could be found. Integrated temperature sensors were capable of measuring local decompression cooling effects and integrated calorimetric sensors measured flow velocities over the range 0.5–13.8 mm s −1 . By this, a better control of high-pressure microfluidic platforms has been achieved. (paper)

Very High Throughput Electrical Cell Lysis and Extraction of Intracellular Compounds Using 3D Carbon Electrodes in Lab-on-a-Chip Devices

Directory of Open Access Journals (Sweden)

Philippe Renaud

2012-08-01

Full Text Available Here we present an electrical lysis throughput of 600 microliters per minute at high cell density (10⁸ yeast cells per ml with 90% efficiency, thus improving the current common throughput of one microliter per minute. We also demonstrate the extraction of intracellular luciferase from mammalian cells with efficiency comparable to off-chip bulk chemical lysis. The goal of this work is to develop a sample preparation module that can act as a stand-alone device or be integrated to other functions already demonstrated in miniaturized devices, including sorting and analysis, towards a true lab-on-a-chip.

Dr. Monaco Examines Lab-on a-Chip

Science.gov (United States)

2003-01-01

Dr. Lisa Monaco, Marshall Space Flight Center's (MSFC's) project scientist for the Lab-on-a-Chip Applications Development (LOCAD) program, examines a lab on a chip. The small dots are actually ports where fluids and chemicals can be mixed or samples can be collected for testing. Tiny channels, only clearly visible under a microscope, form pathways between the ports. Many chemical and biological processes, previously conducted on large pieces of laboratory equipment, can now be performed on these small glass or plastic plates. Monaco and other researchers at MSFC in Huntsville, Alabama, are customizing the chips to be used for many space applications, such as monitoring microbes inside spacecraft and detecting life on other planets. The portable, handheld Lab-on-a Chip Application Development Portable Test System (LOCAD-PTS) made its debut flight aboard Discovery during the STS-116 mission launched December 9, 2006. The system allowed crew members to monitor their environment for problematic contaminants such as yeast, mold, and even E.coli, and salmonella. Once LOCAD-PTS reached the International Space Station (ISS), the Marshall team continued to manage the experiment, monitoring the study from a console in the Payload Operations Center at MSFC. The results of these studies will help NASA researchers refine the technology for future Moon and Mars missions. (NASA/MSFC/D.Stoffer)

Imaging through scattering microfluidic channels by digital holography for information recovery in lab on chip.

Science.gov (United States)

Bianco, V; Paturzo, M; Gennari, O; Finizio, A; Ferraro, P

2013-10-07

We tackle the problem of information recovery and imaging through scattering microfluidic chips by means of digital holography (DH). In many cases the chip can become opalescent due to residual deposits settling down the inner channel faces, biofilm formation, scattering particle uptake by the channel cladding or its damaging by corrosive substances, or even by condensing effect on the exterior channels walls. In these cases white-light imaging is severely degraded and no information is obtainable at all about the flowing samples. Here we investigate the problem of counting and estimating velocity of cells flowing inside a scattering chip. Moreover we propose and test a method based on the recording of multiple digital holograms to retrieve improved phase-contrast images despite the strong scattering effect. This method helps, thanks to DH, to recover information which, otherwise, would be completely lost.

Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient.

Science.gov (United States)

Kim, Ji Hyeon; Sim, Jiyeon; Kim, Hyun-Jung

2018-04-11

Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro , we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

Lab-on-a-chip synthesis of inorganic nanomaterials and quantum dots for biomedical applications.

Science.gov (United States)

Krishna, Katla Sai; Li, Yuehao; Li, Shuning; Kumar, Challa S S R

2013-11-01

The past two decades have seen a dramatic raise in the number of investigations leading to the development of Lab-on-a-Chip (LOC) devices for synthesis of nanomaterials. A majority of these investigations were focused on inorganic nanomaterials comprising of metals, metal oxides, nanocomposites and quantum dots. Herein, we provide an analysis of these findings, especially, considering the more recent developments in this new decade. We made an attempt to bring out the differences between chip-based as well as tubular continuous flow systems. We also cover, for the first time, various opportunities the tools from the field of computational fluid dynamics provide in designing LOC systems for synthesis inorganic nanomaterials. Particularly, we provide unique examples to demonstrate that there is a need for concerted effort to utilize LOC devices not only for synthesis of inorganic nanomaterials but also for carrying out superior in vitro studies thereby, paving the way for faster clinical translation. Even though LOC devices with the possibility to carry out multi-step syntheses have been designed, surprisingly, such systems have not been utilized for carrying out simultaneous synthesis and bio-functionalization of nanomaterials. While traditionally, LOC devices are primarily based on microfluidic systems, in this review article, we make a case for utilizing millifluidic systems for more efficient synthesis, bio-functionalization and in vitro studies of inorganic nanomaterials tailor-made for biomedical applications. Finally, recent advances in the field clearly point out the possibility for pushing the boundaries of current medical practices towards personalized health care with a vision to develop automated LOC-based instrumentation for carrying out simultaneous synthesis, bio-functionalization and in vitro evaluation of inorganic nanomaterials for biomedical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Low-temperature bonded glass-membrane microfluidic device for in vitro organ-on-a-chip cell culture models

Science.gov (United States)

Pocock, Kyall J.; Gao, Xiaofang; Wang, Chenxi; Priest, Craig; Prestidge, Clive A.; Mawatari, Kazuma; Kitamori, Takehiko; Thierry, Benjamin

2015-12-01

The integration of microfluidics with living biological systems has paved the way to the exciting concept of "organson- a-chip", which aims at the development of advanced in vitro models that replicate the key features of human organs. Glass based devices have long been utilised in the field of microfluidics but the integration of alternative functional elements within multi-layered glass microdevices, such as polymeric membranes, remains a challenge. To this end, we have extended a previously reported approach for the low-temperature bonding of glass devices that enables the integration of a functional polycarbonate porous membrane. The process was initially developed and optimised on specialty low-temperature bonding equipment (μTAS2001, Bondtech, Japan) and subsequently adapted to more widely accessible hot embosser units (EVG520HE Hot Embosser, EVG, Austria). The key aspect of this method is the use of low temperatures compatible with polymeric membranes. Compared to borosilicate glass bonding (650 °C) and quartz/fused silica bonding (1050 °C) processes, this method maintains the integrity and functionality of the membrane (Tg 150 °C for polycarbonate). Leak tests performed showed no damage or loss of integrity of the membrane for up to 150 hours, indicating sufficient bond strength for long term cell culture. A feasibility study confirmed the growth of dense and functional monolayers of Caco-2 cells within 5 days.

Optically Driven Mobile Integrated Micro-Tools for a Lab-on-a-Chip

Directory of Open Access Journals (Sweden)

Yi-Jui Liu

2013-04-01

Full Text Available This study proposes an optically driven complex micromachine with an Archimedes microscrew as the mechanical power, a sphere as a coupler, and three knives as the mechanical tools. The micromachine is fabricated by two-photon polymerization and is portably driven by optical tweezers. Because the microscrew can be optically trapped and rotates spontaneously, it provides driving power for the complex micro-tools. In other words, when a laser beam focuses on the micromachine, the microscrew is trapped toward the focus point and simultaneously rotates. A demonstration showed that the integrated micromachines are grasped by the optical tweezers and rotated by the Archimedes screw. The rotation efficiencies of the microrotors with and without knives are 1.9 rpm/mW and 13.5 rpm/mW, respectively. The micromachine can also be portably dragged along planed routes. Such Archimedes screw-based optically driven complex mechanical micro-tools enable rotation similar to moving machines or mixers, which could contribute to applications for a biological microfluidic chip or a lab-on-a-chip.

An integrated lab-on-chip for rapid identification and simultaneous differentiation of tropical pathogens.

Directory of Open Access Journals (Sweden)

Jeslin J L Tan

Full Text Available Tropical pathogens often cause febrile illnesses in humans and are responsible for considerable morbidity and mortality. The similarities in clinical symptoms provoked by these pathogens make diagnosis difficult. Thus, early, rapid and accurate diagnosis will be crucial in patient management and in the control of these diseases. In this study, a microfluidic lab-on-chip integrating multiplex molecular amplification and DNA microarray hybridization was developed for simultaneous detection and species differentiation of 26 globally important tropical pathogens. The analytical performance of the lab-on-chip for each pathogen ranged from 102 to 103 DNA or RNA copies. Assay performance was further verified with human whole blood spiked with Plasmodium falciparum and Chikungunya virus that yielded a range of detection from 200 to 4×105 parasites, and from 250 to 4×107 PFU respectively. This lab-on-chip was subsequently assessed and evaluated using 170 retrospective patient specimens in Singapore and Thailand. The lab-on-chip had a detection sensitivity of 83.1% and a specificity of 100% for P. falciparum; a sensitivity of 91.3% and a specificity of 99.3% for P. vivax; a positive 90.0% agreement and a specificity of 100% for Chikungunya virus; and a positive 85.0% agreement and a specificity of 100% for Dengue virus serotype 3 with reference methods conducted on the samples. Results suggested the practicality of an amplification microarray-based approach in a field setting for high-throughput detection and identification of tropical pathogens.

PMMA to SU-8 bonding for polymer based lab-on-a-chip systems with integrated optics

DEFF Research Database (Denmark)

Olsen, Brian Bilenberg; Nielsen, Theodor; Clausen, Bjarne Hans

2004-01-01

We present an adhesive bonding technique developed for SU-8 based "lab-on-a-chip"- systems with integrated optical components. Microfluidic channels and optical components (e.g. wave-guides) are defined in SU-8 photoresist on a Pyrex glass substrate. The microfluidic channels are sealed by a second...... Pyrex substrate, bonded on top of the cross-linked SU-8 structure using an inter- mediate layer of 950K molecular weight poly-methylmethacrylate (PMMA). Due to a lower refractive index of PMMA, this bonding technique offers optical waveguiding in the SU-8 structures in combination with good sealing...... of the microfluidic channels. The bonding technique is investigated with respect to bonding temperature in the range of 50 - 150 degr. C and at bonding forces of 1000 N and 2000 N on a 4-inch wafer. A maximum bonding strength of 16 MPa is achieved for the PMMA to SU-8 bonding at a bonding temperature of 110 degr. C...

Integration of microcoils for on-chip immunosensors based on magnetic nanoparticles capture

Directory of Open Access Journals (Sweden)

Olivier Lefebvre

2017-04-01

Full Text Available Immunoassays using magnetic nanoparticles (MNP are generally performed under the control of permanent magnet close to the micro-tube of reaction. Using a magnet gives a powerful method for driving MNP but remains unreliable or insufficient for a fully integrated immunoassay on lab-on-chip. The aim of this study is to develop a novel lab-on-chip concept for high efficient immunoassays to detect ovalbumin (Biodefense model molecule with microcoils employed for trapping MNP during the biofunctionalization steps. The objectives are essentially to optimize their efficiency for biological recognition by assuring a better bioactivity (antibodies-ovalbumin, and detect small concentrations of the targeted protein (~10 pg/mL. In this work, we studied the response of immunoassays complex function of ovalbumin concentration. The impact of MNP diameter in the biografting protocol was studied and permitted to choose a convenient MNP size for efficient biorecognition. We realized different immunoassays by controlling MNP in test tube and in microfluidic device using a permanent magnet. The comparison between these two experiments allows us to highlight an improvement of the limit of detection in microfluidic conditions by controlling MNP trapping with a magnet. Keywords: Bacteria, Lab-on-chip, ELISA, Magnetic nanoparticles, Ovalbumin, Microcoils, Fluorescent microscopy

Multi-color fluorescent DNA analysis in an integrated optofluidic lab on a chip

OpenAIRE

Dongre, C.

2010-01-01

Abstract: Sorting and sizing of DNA molecules within the human genome project has enabled the genetic mapping of various illnesses. Furthermore by employing tiny lab-on-a-chip device, integrated DNA sequencing and genetic diagnostics have become feasible. We present the combination of capillary electrophoresis with laser-induced fluorescence for optofluidic integration toward an on-chip bio-analysis tool. Integrated optical fluorescence excitation allows for a high spatial resolution (12 μm) ...

Characterizations of gas purge valves for liquid alignment and gas removal in a microfluidic chip

International Nuclear Information System (INIS)

Chuang, Han-Sheng; Thakur, Raviraj; Wereley, Steven T

2012-01-01

Two polydimethylsiloxane (PDMS) gas purge valves for excessive gas removal in general lab-on-a-chip applications are presented in this paper. Both valves are devised based on a three-layer configuration comprising a top layer for liquid channels, a membrane and a bottom layer for gas channels. The pneumatic valves work as a normal gateway for fluids when the membrane is bulged down (open state) by vacuum or pushed up (closed state) by pressure. In the closed state, the air in front of a liquid can be removed through a small notch or a permeable PDMS membrane by compressing the liquid. The purge valve with a small notch across its valve seat, termed surface-tension (ST) valve, can be operated with pressure under 11.5 kPa. The liquid is mainly retained by the surface tension resulting from the hydrophobic channel walls. In contrast, the purge valve with vacuum-filled grooves adjacent to a liquid channel, termed gas-permeation (GP) valve, can be operated at pressure above 5.5 kPa. Based on the principle of gas permeation, the excessive air can be slowly removed through the vent grooves. Detailed evaluations of both valves in a pneumatically driven microfluidic chip were conducted. Specifically, the purge valves enable users to remove gas and passively align liquids at desired locations without using sensing devices or feedback circuits. Finally, a rapid mixing reaction was successfully performed with the GP valves, showing their practicability as incorporated in a microfluidic chip. (paper)

A review on recent developments for biomolecule separation at analytical scale using microfluidic devices.

Science.gov (United States)

Tetala, Kishore K R; Vijayalakshmi, M A

2016-02-04

Microfluidic devices with their inherent advantages like the ability to handle 10(-9) to 10(-18) L volume, multiplexing of microchannels, rapid analysis and on-chip detection are proving to be efficient systems in various fields of life sciences. This review highlights articles published since 2010 that reports the use of microfluidic devices to separate biomolecules (DNA, RNA and proteins) using chromatography principles (size, charge, hydrophobicity and affinity) along with microchip capillary electrophoresis, isotachophoresis etc. A detailed overview of stationary phase materials and the approaches to incorporate them within the microchannels of microchips is provided as well as a brief overview of chemical methods to immobilize ligand(s). Furthermore, we review research articles that deal with microfluidic devices as analytical tools for biomolecule (DNA, RNA and protein) separation. Copyright © 2015 Elsevier B.V. All rights reserved.

Dye-based coatings for hydrophobic valves and their application to polymer labs-on-a-chip

Science.gov (United States)

Riegger, L.; Mielnik, M. M.; Gulliksen, A.; Mark, D.; Steigert, J.; Lutz, S.; Clad, M.; Zengerle, R.; Koltay, P.; Hoffmann, J.

2010-04-01

We provide a method for the selective surface patterning of microfluidic chips with hydrophobic fluoropolymers which is demonstrated by the fabrication of hydrophobic valves via dispensing. It enables efficient optical quality control for the surface patterning thus permitting the low-cost production of highly reproducible hydrophobic valves. Specifically, different dyes for fluoropolymers enabling visual quality control (QC) are investigated, and two fluoropolymer-solvent-dye solutions based on fluorescent quantum dots (QD) and carbon black (CB) are presented in detail. The latter creates superhydrophobic surfaces on arbitrary substrates, e.g. chips made from cyclic olefin copolymer (COC, water contact angle = 157.9°), provides good visibility for the visual QC in polymer labs-on-a-chip and increases the burst pressures of the hydrophobic valves. Finally, an application is presented which aims at the on-chip amplification of mRNA based on defined flow control by hydrophobic valves is presented. Here, the optimization based on QC in combination with the Teflon-CB coating improves the burst pressure reproducibility from 14.5% down to 6.1% compared to Teflon-coated valves.

Lab-on-a-Chip Pathogen Sensors for Food Safety

Directory of Open Access Journals (Sweden)

Bumsang Kim

2012-08-01

Full Text Available There have been a number of cases of foodborne illness among humans that are caused by pathogens such as Escherichia coli O157:H7, Salmonella typhimurium, etc. The current practices to detect such pathogenic agents are cell culturing, immunoassays, or polymerase chain reactions (PCRs. These methods are essentially laboratory-based methods that are not at all real-time and thus unavailable for early-monitoring of such pathogens. They are also very difficult to implement in the field. Lab-on-a-chip biosensors, however, have a strong potential to be used in the field since they can be miniaturized and automated; they are also potentially fast and very sensitive. These lab-on-a-chip biosensors can detect pathogens in farms, packaging/processing facilities, delivery/distribution systems, and at the consumer level. There are still several issues to be resolved before applying these lab-on-a-chip sensors to field applications, including the pre-treatment of a sample, proper storage of reagents, full integration into a battery-powered system, and demonstration of very high sensitivity, which are addressed in this review article. Several different types of lab-on-a-chip biosensors, including immunoassay- and PCR-based, have been developed and tested for detecting foodborne pathogens. Their assay performance, including detection limit and assay time, are also summarized. Finally, the use of optical fibers or optical waveguide is discussed as a means to improve the portability and sensitivity of lab-on-a-chip pathogen sensors.

Microfluidics on liquid handling stations (μF-on-LHS): an industry compatible chip interface between microfluidics and automated liquid handling stations.

Science.gov (United States)

Waldbaur, Ansgar; Kittelmann, Jörg; Radtke, Carsten P; Hubbuch, Jürgen; Rapp, Bastian E

2013-06-21

We describe a generic microfluidic interface design that allows the connection of microfluidic chips to established industrial liquid handling stations (LHS). A molding tool has been designed that allows fabrication of low-cost disposable polydimethylsiloxane (PDMS) chips with interfaces that provide convenient and reversible connection of the microfluidic chip to industrial LHS. The concept allows complete freedom of design for the microfluidic chip itself. In this setup all peripheral fluidic components (such as valves and pumps) usually required for microfluidic experiments are provided by the LHS. Experiments (including readout) can be carried out fully automated using the hardware and software provided by LHS manufacturer. Our approach uses a chip interface that is compatible with widely used and industrially established LHS which is a significant advancement towards near-industrial experimental design in microfluidics and will greatly facilitate the acceptance and translation of microfluidics technology in industry.

Development of a magnetic lab-on-a-chip for point-of-care sepsis diagnosis

International Nuclear Information System (INIS)

Schotter, Joerg; Shoshi, Astrit; Brueckl, Hubert

2009-01-01

We present design criteria, operation principles and experimental examples of magnetic marker manipulation for our magnetic lab-on-a-chip prototype. It incorporates both magnetic sample preparation and detection by embedded GMR-type magnetoresistive sensors and is optimized for the automated point-of-care detection of four different sepsis-indicative cytokines directly from about 5 μl of whole blood. The sample volume, magnetic particle size and cytokine concentration determine the microfluidic volume, sensor size and dimensioning of the magnetic gradient field generators. By optimizing these parameters to the specific diagnostic task, best performance is expected with respect to sensitivity, analysis time and reproducibility.

Novel immunoassay formats for integrated microfluidic circuits: diffusion immunoassays (DIA)

Science.gov (United States)

Weigl, Bernhard H.; Hatch, Anson; Kamholz, Andrew E.; Yager, Paul

2000-03-01

Novel designs of integrated fluidic microchips allow separations, chemical reactions, and calibration-free analytical measurements to be performed directly in very small quantities of complex samples such as whole blood and contaminated environmental samples. This technology lends itself to applications such as clinical diagnostics, including tumor marker screening, and environmental sensing in remote locations. Lab-on-a-Chip based systems offer many *advantages over traditional analytical devices: They consume extremely low volumes of both samples and reagents. Each chip is inexpensive and small. The sampling-to-result time is extremely short. They perform all analytical functions, including sampling, sample pretreatment, separation, dilution, and mixing steps, chemical reactions, and detection in an integrated microfluidic circuit. Lab-on-a-Chip systems enable the design of small, portable, rugged, low-cost, easy to use, yet extremely versatile and capable diagnostic instruments. In addition, fluids flowing in microchannels exhibit unique characteristics ('microfluidics'), which allow the design of analytical devices and assay formats that would not function on a macroscale. Existing Lab-on-a-chip technologies work very well for highly predictable and homogeneous samples common in genetic testing and drug discovery processes. One of the biggest challenges for current Labs-on-a-chip, however, is to perform analysis in the presence of the complexity and heterogeneity of actual samples such as whole blood or contaminated environmental samples. Micronics has developed a variety of Lab-on-a-Chip assays that can overcome those shortcomings. We will now present various types of novel Lab- on-a-Chip-based immunoassays, including the so-called Diffusion Immunoassays (DIA) that are based on the competitive laminar diffusion of analyte molecules and tracer molecules into a region of the chip containing antibodies that target the analyte molecules. Advantages of this

Multi-color fluorescent DNA analysis in an integrated optofluidic lab on a chip

NARCIS (Netherlands)

Dongre, C.

2010-01-01

Abstract: Sorting and sizing of DNA molecules within the human genome project has enabled the genetic mapping of various illnesses. Furthermore by employing tiny lab-on-a-chip device, integrated DNA sequencing and genetic diagnostics have become feasible. We present the combination of capillary

Fluorimetric urease inhibition assay on a multilayer microfluidic chip with immunoaffinity immobilized enzyme reactors.

Science.gov (United States)

Zhang, Qin; Tang, Xiuwen; Hou, Fenghua; Yang, Jianping; Xie, Zhiyong; Cheng, Zhiyi

2013-10-01

We fabricated a three-layer polydimethylsiloxane (PDMS)-based microfluidic chip for realizing urease inhibition assay with sensitive fluorescence detection. Procedures such as sample prehandling, enzyme reaction, reagent mixing, fluorescence derivatization, and detection can be readily carried out. Urease reactors were prepared by adsorption of rabbit immunoglobulin G (IgG) and immunoreaction with urease-conjugated goat anti-rabbit IgG. Acetohydroxamic acid (AHA) as a competitive inhibitor of urease was tested on the chip. Microfluidically generated gradient concentrations of AHA with substrate (urea) were loaded into urease reactors. After incubation, the produced ammonia was transported out of reactors and then reacted with o-phthalaldehyde (OPA) to generate fluorescent products. Urease inhibition was indicated by a decrease in fluorescence signal detected by microplate reader. The IC50 value of AHA was determined and showed good agreement with that obtained in microplate. The presented device combines several steps of the analytical process with advantages of low reagent consumption, reduced analysis time, and ease of manipulation. This microfluidic approach can be extended to the screening of inhibitory compounds in drug discovery. Copyright © 2013 Elsevier Inc. All rights reserved.

Lab on a chip automates in vitro cell culturing

DEFF Research Database (Denmark)

Perozziello, Gerardo; Møllenbach, Jacob; Laursen, Steen

2012-01-01

A novel in vitro fertilization system is presented based on an incubation chamber and a microfluidic device which serves as advanced microfluidic cultivation chamber. The flow is controlled by hydrostatic height differences and evaporation is avoided with help of mineral oil. Six patient compartm......A novel in vitro fertilization system is presented based on an incubation chamber and a microfluidic device which serves as advanced microfluidic cultivation chamber. The flow is controlled by hydrostatic height differences and evaporation is avoided with help of mineral oil. Six patient...... compartments allow six simultaneous temperature and pH controlled cultivations with 12 embryos with continuous logging of the monitoring data. Two media can be controlled with help of opening or closing of openings at the microfluidic disposable devices. The flow rates through the single cell compartments can...

Detection and classification of ebola on microfluidic chips

Science.gov (United States)

Lin, Xue; Jin, Xiangyu; Fan, Yunqian; Huang, Qin; Kou, Yue; Zu, Guo; Huang, Shiguang; Liu, Xiaosheng; Huang, Guoliang

2016-10-01

Point-of-care testing (POCT) for an infectious diseases is the prerequisite to control of the disease and limitation of its spread. A microfluidic chip for detection and classification of four strains of Ebola virus was developed and evaluated. This assay was based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific primers for Ebola Zaire virus, Ebola Sudan virus, Ebola Tai Forest virus and Ebola Bundibugyo virus were designed. The sensitivity of the microfluidic chip was under 103 copies per milliliter, as determined by ten repeated tests. This assay is unique in its ability to enable diagnosis of the Ebola infections and simultaneous typing of Ebola virus on a single chip. It offers short reaction time, ease of use and high specificity. These features should enable POCT in remote area during outbreaks of Ebola virus.

Electrochemical detection on electrowetting-on-dielectric digital microfluidic chip.

Science.gov (United States)

Karuwan, Chanpen; Sukthang, Kreeta; Wisitsoraat, Anurat; Phokharatkul, Ditsayut; Patthanasettakul, Viyapol; Wechsatol, Wishsanuruk; Tuantranont, Adisorn

2011-06-15

In this work, the use of three-electrode electrochemical sensing system with an electrowetting-on-dielectric (EWOD) digital microfluidic device is reported for quantitative analysis of iodide. T-junction EWOD mixer device was designed using arrays of 50-μm spaced square electrodes for mixing buffer reagent and analyte droplets. For fabrication of EWOD chips, 5-μm thick silver EWOD electrodes were formed on a glass substrate by means of sputtering and lift-off process. PDMS and Teflon thin films were then coated on the electrodes by spin coating to yield hydrophobic surface. An external three-electrode system consisting of Au working, Ag reference and Pt auxiliary wires were installed over EWOD electrodes at the end of T-junction mixer. In experiment, a few-microliter droplets of Tris buffer and iodide solutions were moved toward the mixing junction and transported toward electrochemical electrodes by EWOD process. A short processing time within seconds was achieved at EWOD applied voltage of 300V. The analyte droplets mixed with different concentrations were successfully analyzed by cyclic voltametry. Therefore, the combination of EWOD digital microfluidic and electrochemical sensing system has successfully been demonstrated for rapid chemical analysis with minimal reagent consumption. Copyright © 2011 Elsevier B.V. All rights reserved.

Microfluidic Devices for Drug Delivery Systems and Drug Screening

Science.gov (United States)

Kompella, Uday B.; Damiati, Safa A.

2018-01-01

Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. PMID:29462948

About Small Streams and Shiny Rocks: Macromolecular Crystal Growth in Microfluidics

Science.gov (United States)

vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

2002-01-01

We are developing a novel technique with which we have grown diffraction quality protein crystals in very small volumes, utilizing chip-based, microfluidic ("LabChip") technology. With this technology volumes smaller than achievable with any laboratory pipette can be dispensed with high accuracy. We have performed a feasibility study in which we crystallized several proteins with the aid of a LabChip device. The protein crystals are of excellent quality as shown by X-ray diffraction. The advantages of this new technology include improved accuracy of dispensing for small volumes, complete mixing of solution constituents without bubble formation, highly repeatable recipe and growth condition replication, and easy automation of the method. We have designed a first LabChip device specifically for protein crystallization in batch mode and can reliably dispense and mix from a range of solution constituents. We are currently testing this design. Upon completion additional crystallization techniques, such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility aboard the International Space Station.

Lab-on-paper micro- and nano-analytical devices: Fabrication, modification, detection and emerging applications

International Nuclear Information System (INIS)

Xu, Yuanhong; Liu, Mengli; Kong, Na; Liu, Jingquan

2016-01-01

Paper-based chips (PB-chips; also referred to as lab-on-paper chips) are using patterned paper as a substrate in a lab-on-a-chip platform. They represent an outstanding technique for fabrication of analytical devices for multiplex analyte assays. Typical features include low-cost, portability, disposability and small sample consumption. This review (with 211 refs.) gives a comprehensive and critical insight into current trends in terms of materials and techniques for use in fabrication, modification and detection. Following an introduction into the principles of PB-chips, we discuss features of using paper in lab-on-a-chip devices and the proper choice of paper. We then discuss the versatile methods known for fabrication of PB-chips (ranging from photolithography, plasma treatment, ink jet etching, plotting, to printing including flexographic printing). The modification of PB-chips with micro- and nano-materials possessing superior optical or electronic properties is then reviewed, and the final section covers detection techniques (such as colorimetry, electrochemistry, electrochemiluminescence and chemiluminescence) along with specific (bio)analytical examples. A conclusion and outlook section discusses the challenges and future prospectives in this field. (author)

[Development of molecular detection of food-borne pathogenic bacteria using miniaturized microfluidic devices].

Science.gov (United States)

Iván, Kristóf; Maráz, Anna

2015-12-20

Detection and identification of food-borne pathogenic bacteria are key points for the assurance of microbiological food safety. Traditional culture-based methods are more and more replaced by or supplemented with nucleic acid based molecular techniques, targeting specific (preferably virulence) genes in the genomes. Internationally validated DNA amplification - most frequently real-time polymerase chain reaction - methods are applied by the food microbiological testing laboratories for routine analysis, which will result not only in shortening the time for results but they also improve the performance characteristics (e.g. sensitivity, specificity) of the methods. Beside numerous advantages of the polymerase chain reaction based techniques for routine microbiological analysis certain drawbacks have to be mentioned, such as the high cost of the equipment and reagents, as well as the risk of contamination of the laboratory environment by the polymerase chain reaction amplicons, which require construction of an isolated laboratory system. Lab-on-a-chip systems can integrate most of these laboratory processes within a miniaturized device that delivers the same specificity and reliability as the standard protocols. The benefits of miniaturized devices are: simple - often automated - use, small overall size, portability, sterility due to single use possibility. These miniaturized rapid diagnostic tests are being researched and developed at the best research centers around the globe implementing various sample preparation and molecular DNA amplification methods on-chip. In parallel, the aim of the authors' research is to develop microfluidic Lab-on-a-chip devices for the detection and identification of food-borne pathogenic bacteria.

The influence of polydimethylsiloxane curing ratio on capillary pressure in microfluidic devices

International Nuclear Information System (INIS)

Viola, Ilenia; Zacheo, Antonella; Arima, Valentina; Aricò, Antonino S.; Cortese, Barbara; Manca, Michele; Zocco, Anna; Taurino, Antonietta; Rinaldi, Ross

2012-01-01

Investigations on surface properties of poly(dimethylsiloxane) (PDMS) are justified by its large application ranges especially as coating polymer in fluidic devices. At a micrometer scale, the liquid dynamics is strongly modified by interactions with a solid surface. A crucial parameter for this process is microchannel wettability that can be tuned by acting on surface chemistry and topography. In literature, a number of multi-step, time and cost consuming chemical and physical procedures are reported. Here we selectively modify both wetting and mechanical properties by a single step treatment. Changes of PDMS surface were investigated by X-ray photoelectron spectroscopy and atomic force microscopy and the effects of interface properties on the liquid displacement inside a microfluidic system were evaluated. The negative capillary pressure obtained tailoring the PDMS wettability is believed to be promising to accurately control sample leakage inside integrated lab-on-chip by acting on the liquid confinement and thus to reduce the sample volume, liquid drying as well as cross-contamination during the operation.

In situ monitoring using Lab on Chip devices, with particular reference to dissolved silica.

Science.gov (United States)

Turner, G. S. C.; Loucaides, S.; Slavik, G. J.; Owsianka, D. R.; Beaton, A.; Nightingale, A.; Mowlem, M. C.

2016-02-01

In situ sensors are attractive alternatives to discrete sampling of natural waters, offering the potential for sustained long term monitoring and eliminating the need for sample handling. This can reduce sample contamination and degradation. In addition, sensors can be clustered into multi-parameter observatories and networked to provide both spatial and time series coverage. High resolution, low cost, and long term monitoring are the biggest advantages of these technologies to oceanographers. Microfluidic technology miniaturises bench-top assay systems into portable devices, known as a `lab on a chip' (LOC). The principle advantages of this technology are low power consumption, simplicity, speed, and stability without compromising on quality (accuracy, precision, selectivity, sensitivity). We have successfully demonstrated in situ sensors based on this technology for the measurement of pH, nitrate and nitrite. Dissolved silica (dSi) is an important macro-nutrient supporting a major fraction of oceanic primary production carried out by diatoms. The biogeochemical Si cycle is undergoing significant modifications due to human activities, which affects availability of dSi, and consequently primary production. Monitoring dSi concentrations is therefore critical in increasing our understanding of the biogeochemical Si cycle to predict and manage anthropogenic perturbations. The standard bench top air segmented flow technique utilising the reduction of silicomolybdic acid with spectrophotometric detection has been miniaturised into a LOC system; the target limit of detection is 1 nM, with ± 5% accuracy and 3% precision. Results from the assay optimisation are presented along with reagent shelf life to demonstrate the robustness of the chemistry. Laboratory trials of the sensor using ideal solutions and environmental samples in environmentally relevant conditions (temperature, pressure) are discussed, along with an overview of our current LOC analytical capabilities.

Optical manipulation with two beam traps in microfluidic polymer systems

DEFF Research Database (Denmark)

Khoury Arvelo, Maria; Matteucci, Marco; Sørensen, Kristian Tølbøl

2015-01-01

An optical trapping system with two opposing laser beams, also known as the optical stretcher, are naturally constructed inside a microfluidic lab-on-chip system. We present and compare two approaches to combine a simple microfluidic system with either waveguides directly written in the microflui......An optical trapping system with two opposing laser beams, also known as the optical stretcher, are naturally constructed inside a microfluidic lab-on-chip system. We present and compare two approaches to combine a simple microfluidic system with either waveguides directly written...

A simple method of fabricating mask-free microfluidic devices for biological analysis.

KAUST Repository

Yi, Xin

2010-09-07

We report a simple, low-cost, rapid, and mask-free method to fabricate two-dimensional (2D) and three-dimensional (3D) microfluidic chip for biological analysis researches. In this fabrication process, a laser system is used to cut through paper to form intricate patterns and differently configured channels for specific purposes. Bonded with cyanoacrylate-based resin, the prepared paper sheet is sandwiched between glass slides (hydrophilic) or polymer-based plates (hydrophobic) to obtain a multilayer structure. In order to examine the chip\\'s biocompatibility and applicability, protein concentration was measured while DNA capillary electrophoresis was carried out, and both of them show positive results. With the utilization of direct laser cutting and one-step gas-sacrificing techniques, the whole fabrication processes for complicated 2D and 3D microfluidic devices are shorten into several minutes which make it a good alternative of poly(dimethylsiloxane) microfluidic chips used in biological analysis researches.

On-chip integrated lasers for biophotonic applications

DEFF Research Database (Denmark)

Mappes, Timo; Wienhold, Tobias; Bog, Uwe

Meeting the need of biomedical users, we develop disposable Lab-on-a-Chip systems based on commercially available polymers. We are combining passive microfluidics with active optical elements on-chip by integrating multiple solid-state and liquid-core lasers. While covering a wide range of laser ...

A 3D printed microfluidic perfusion device for multicellular spheroid cultures.

Science.gov (United States)

Ong, Louis Jun Ye; Islam, Anik; DasGupta, Ramanuj; Iyer, Narayanan Gopalakkrishna; Leo, Hwa Liang; Toh, Yi-Chin

2017-09-11

The advent of 3D printing technologies promises to make microfluidic organ-on-chip technologies more accessible for the biological research community. To date, hydrogel-encapsulated cells have been successfully incorporated into 3D printed microfluidic devices. However, there is currently no 3D printed microfluidic device that can support multicellular spheroid culture, which facilitates extensive cell-cell contacts important for recapitulating many multicellular functional biological structures. Here, we report a first instance of fabricating a 3D printed microfluidic cell culture device capable of directly immobilizing and maintaining the viability and functionality of 3D multicellular spheroids. We evaluated the feasibility of two common 3D printing technologies i.e. stereolithography (SLA) and PolyJet printing, and found that SLA could prototype a device comprising of cell immobilizing micro-structures that were housed within a microfluidic network with higher fidelity. We have also implemented a pump-free perfusion system, relying on gravity-driven flow to perform medium perfusion in order to reduce the complexity and footprint of the device setup, thereby improving its adaptability into a standard biological laboratory. Finally, we demonstrated the biological performance of the 3D printed device by performing pump-free perfusion cultures of patient-derived parental and metastatic oral squamous cell carcinoma tumor and liver cell (HepG2) spheroids with good cell viability and functionality. This paper presents a proof-of-concept in simplifying and integrating the prototyping and operation of a microfluidic spheroid culture device, which will facilitate its applications in various drug efficacy, metabolism and toxicity studies.

Recent advances in lab-on-a-chip for biosensing applications

DEFF Research Database (Denmark)

Lafleur, Josiane P.; Jönsson, Alexander; Senkbeil, Silja

2016-01-01

The marriage of highly sensitive biosensor designs with the versatility in sample handling and fluidic manipulation offered by lab-on-a-chip systems promises to yield powerful tools for analytical and, in particular, diagnostic applications. The field where these two technologies meet is rapidly...... improvements to existing methods. Recent examples, showing a staggering variety of lab-on-a-chip systems for biosensing applications, are presented, tabularized for overview, and briefly discussed....

"Connecting worlds - a view on microfluidics for a wider application".

Science.gov (United States)

Fernandes, Ana C; Gernaey, Krist V; Krühne, Ulrich

From its birth, microfluidics has been referenced as a revolutionary technology and the solution to long standing technological and sociological issues, such as detection of dilute compounds and personalized healthcare. Microfluidics has for example been envisioned as: (1) being capable of miniaturizing industrial production plants, thereby increasing their automation and operational safety at low cost; (2) being able to identify rare diseases by running bioanalytics directly on the patient's skin; (3) allowing health diagnostics in point-of-care sites through cheap lab-on-a-chip devices. However, the current state of microfluidics, although technologically advanced, has so far failed to reach the originally promised widespread use. In this paper, some of the aspects are identified and discussed that have prevented microfluidics from reaching its full potential, especially in the chemical engineering and biotechnology fields, focusing mainly on the specialization on a single target of most microfluidic devices and offering a perspective on the alternate, multi-use, "plug and play" approach. Increasing the flexibility of microfluidic platforms, by increasing their compatibility with different substrates, reactions and operation conditions, and other microfluidic systems is indeed of surmount importance and current academic and industrial approaches to modular microfluidics are presented. Furthermore, two views on the commercialization of plug-and-play microfluidics systems, leading towards improved acceptance and more widespread use, are introduced. A brief review of the main materials and fabrication strategies used in these fields, is also presented. Finally, a step-wise guide towards the development of microfluidic systems is introduced with special focus on the integration of sensors in microfluidics. The proposed guidelines are then applied for the development of two different example platforms, and to three examples taken from literature. With this work, we

Enabling rapid behavioral ecotoxicity studies using an integrated lab-on-a-chip systems

Science.gov (United States)

Huang, Yushi; Nugegoda, Dayanthi; Wlodkowic, Donald

2015-12-01

Behavioral ecotoxicity tests are gaining an increasing recognition in environmental toxicology. Behavior of sensitive bioindicator species can change rapidly in response to an acute exposure to contaminants and thus has a much higher sensitivity as compared to conventional LC50 mortality tests. Furthermore, behavioral endpoints seems to be very good candidates to develop early-warning biomonitoring systems needed for rapid chemical risk assessment. Behavioral tests are non-invasive, fast, do not harm indicator organisms (behavioural changes are very rapid) and are thus fully compatible with 3R (Replacement - Reduction - Refinement) principle encouraging alternatives to conventional animal testing. These characteristics are essential when designing improved ecotoxicity tests for chemical risk assessment. In this work, we present a pilot development of miniaturized Lab-on-a-Chip (LOC) devices for studying toxin avoidance behaviors of small aquatic crustaceans. As an investigative tool, LOCs represent a new direction that may miniaturize and revolutionize behavioral ecotoxicology. Specifically our innovative microfluidic prototype: (i) enables convening "caging" of specimens for real-time videomicroscopy; (ii) eliminates the evaporative water loss thus providing an opportunity for long-term behavioral studies; (iii) exploits laminar fluid flow under low Reynolds numbers to generate discrete domains and gradients enabling for the first time toxin avoidance studies on small aquatic crustaceans; (iv) integrates off-the-chip mechatronic interfaces and video analysis algorithms for single animal movement analysis. We provide evidence that by merging innovative bioelectronic and biomicrofluidic technologies we can deploy inexpensive and reliable systems for culture, electronic tracking and complex computational analysis of behavior of bioindicator organisms.

Modeling and Analysis of an Opto-Fluidic Sensor for Lab-on-a-Chip Applications

Directory of Open Access Journals (Sweden)

Venkatesha Muniswamy

2018-03-01

Full Text Available In this work modeling and analysis of an integrated opto-fluidic sensor, with a focus on achievement of single mode optical confinement and continuous flow of microparticles in the microfluidic channel for lab-on-a-chip (LOC sensing application is presented. This sensor consists of integrated optical waveguides, microfluidic channel among other integrated optical components. A continuous flow of microparticles in a narrow fluidic channel is achieved by maintaining the two sealed chambers at different temperatures and by maintaining a constant pressure of 1 Pa at the centroid of narrow fluidic channel geometry. The analysis of silicon on insulator (SOI integrated optical waveguide at an infrared wavelength of 1550 nm for single mode sensing operation is presented. The optical loss is found to be 5.7 × 10−4 dB/cm with an effective index of 2.3. The model presented in this work can be effectively used to detect the nature of microparticles and continuous monitoring of pathological parameters for sensing applications.

Smartphone technology can be transformative to the deployment of lab-on-chip diagnostics.

Science.gov (United States)

Erickson, David; O'Dell, Dakota; Jiang, Li; Oncescu, Vlad; Gumus, Abdurrahman; Lee, Seoho; Mancuso, Matthew; Mehta, Saurabh

2014-09-07

The rapid expansion of mobile technology is transforming the biomedical landscape. By 2016 there will be 260 M active smartphones in the US and millions of health accessories and software "apps" running off them. In parallel with this have come major technical achievements in lab-on-a-chip technology leading to incredible new biochemical sensors and molecular diagnostic devices. Despite these advancements, the uptake of lab-on-a-chip technologies at the consumer level has been somewhat limited. We believe that the widespread availability of smartphone technology and the capabilities they offer in terms of computation, communication, social networking, and imaging will be transformative to the deployment of lab-on-a-chip type technology both in the developed and developing world. In this paper we outline why we believe this is the case, the new business models that may emerge, and detail some specific application areas in which this synergy will have long term impact, namely: nutrition monitoring and disease diagnostics in limited resource settings.

Dimensional metrology of lab-on-a-chip internal structures: a comparison of optical coherence tomography with confocal fluorescence microscopy.

Science.gov (United States)

Reyes, D R; Halter, M; Hwang, J

2015-07-01

The characterization of internal structures in a polymeric microfluidic device, especially of a final product, will require a different set of optical metrology tools than those traditionally used for microelectronic devices. We demonstrate that optical coherence tomography (OCT) imaging is a promising technique to characterize the internal structures of poly(methyl methacrylate) devices where the subsurface structures often cannot be imaged by conventional wide field optical microscopy. The structural details of channels in the devices were imaged with OCT and analyzed with an in-house written ImageJ macro in an effort to identify the structural details of the channel. The dimensional values obtained with OCT were compared with laser-scanning confocal microscopy images of channels filled with a fluorophore solution. Attempts were also made using confocal reflectance and interferometry microscopy to measure the channel dimensions, but artefacts present in the images precluded quantitative analysis. OCT provided the most accurate estimates for the channel height based on an analysis of optical micrographs obtained after destructively slicing the channel with a microtome. OCT may be a promising technique for the future of three-dimensional metrology of critical internal structures in lab-on-a-chip devices because scans can be performed rapidly and noninvasively prior to their use. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

The development of lab-on-a-chip fabricated from two molds

Science.gov (United States)

Pramuanjaroenkij, A.; Bunta, J.; Thiangpadung, J.; Sansaradee, S.; Kamsopa, P.; Sodsai, S.; Vichainsan, S.; Wongpanit, K.; Maturos, T.; Lomas, T.; Tuantranont, A.; Cetin, B.; Phankhoksoong, S.; Tongkratoke, A.

2018-01-01

Development of diagnostic technique of microfluidic or lab-on-a-chip (LOCs) is currently of great interest for researchers and inventors for their many advantages. It can be used as a real laboratory was many ways to help to the diagnosis faster. This research aims to develop Polydimethylsiloxane (PDMS) lab-on-a-chip (LOCs) which were produced from different molds; the silicon wafer mold and the stainless mold to investigate the flow of the biological sample as the flow in nanochannels. In addition, this research proposes a means to leakage and the blockage of the channel flow. The experimental results were found that the LOCs casted from the silicon wafer mold sandwiched by both the plasma cleaner machine and H shaped acrylic sheets showed leakages around the electrode areas because the first new electrodes were too thick, the proper thickness of the nickel electrode was at 0.05 millimeters. The LOCs casted from the stainless mold were inserted by the nickel electrodes produced by the from the prototype shaped electroplating process; this LOCs using nickel plated electrodes 2 times to make a groove on the nickel electrode backsides when pouring the PDMS into the LOCs casted from the stainless mold. It was found that PDMS was able to flow under the nickel electrode and the PDMS sheet could stick with the glass slide smoothly. In conclusion, it was possible to develop these LOC designs and new electrode fabrications continually under helps from Micro-Electro-Mechanical system, Thailand National Electronics and Computer Technology Center, since causes of the LOC problems were found, and demonstrated the feasibility of developing the LOCs for chemical detection and disease diagnostics.

Open-Source Wax RepRap 3-D Printer for Rapid Prototyping Paper-Based Microfluidics.

Science.gov (United States)

Pearce, J M; Anzalone, N C; Heldt, C L

2016-08-01

The open-source release of self-replicating rapid prototypers (RepRaps) has created a rich opportunity for low-cost distributed digital fabrication of complex 3-D objects such as scientific equipment. For example, 3-D printable reactionware devices offer the opportunity to combine open hardware microfluidic handling with lab-on-a-chip reactionware to radically reduce costs and increase the number and complexity of microfluidic applications. To further drive down the cost while improving the performance of lab-on-a-chip paper-based microfluidic prototyping, this study reports on the development of a RepRap upgrade capable of converting a Prusa Mendel RepRap into a wax 3-D printer for paper-based microfluidic applications. An open-source hardware approach is used to demonstrate a 3-D printable upgrade for the 3-D printer, which combines a heated syringe pump with the RepRap/Arduino 3-D control. The bill of materials, designs, basic assembly, and use instructions are provided, along with a completely free and open-source software tool chain. The open-source hardware device described here accelerates the potential of the nascent field of electrochemical detection combined with paper-based microfluidics by dropping the marginal cost of prototyping to nearly zero while accelerating the turnover between paper-based microfluidic designs. © 2016 Society for Laboratory Automation and Screening.

Route to one-step microstructure mold fabrication for PDMS microfluidic chip

Science.gov (United States)

Lv, Xiaoqing; Geng, Zhaoxin; Fan, Zhiyuan; Wang, Shicai; Su, Yue; Fang, Weihao; Pei, Weihua; Chen, Hongda

2018-04-01

The microstructure mold fabrication for PDMS microfluidic chip remains complex and time-consuming process requiring special equipment and protocols: photolithography and etching. Thus, a rapid and cost-effective method is highly needed. Comparing with the traditional microfluidic chip fabricating process based on the micro-electromechanical system (MEMS), this method is simple and easy to implement, and the whole fabrication process only requires 1-2 h. Different size of microstructure from 100 to 1000 μm was fabricated, and used to culture four kinds of breast cancer cell lines. Cell viability and morphology was assessed when they were cultured in the micro straight channels, micro square holes and the bonding PDMS-glass microfluidic chip. The experimental results indicate that the microfluidic chip is good and meet the experimental requirements. This method can greatly reduce the process time and cost of the microfluidic chip, and provide a simple and effective way for the structure design and in the field of biological microfabrications and microfluidic chips.

Lab-on-a-Chip Device for Rapid Measurement of Vitamin D Levels.

Science.gov (United States)

Peter, Harald; Bistolas, Nikitas; Schumacher, Soeren; Laurisch, Cecilia; Guest, Paul C; Höller, Ulrich; Bier, Frank F

2018-01-01

Lab-on-a-chip assays allow rapid analysis of one or more molecular analytes on an automated user-friendly platform. Here we describe a fully automated assay and readout for measurement of vitamin D levels in less than 15 min using the Fraunhofer in vitro diagnostics platform. Vitamin D (25-hydroxyvitamin D 3 [25(OH)D 3 ]) dilution series in buffer were successfully tested down to 2 ng/mL. This could be applied in the future as an inexpensive point-of-care analysis for patients suffering from a variety of conditions marked by vitamin D deficiencies.

Rapid prototyping of 2D glass microfluidic devices based on femtosecond laser assisted selective etching process

Science.gov (United States)

Kim, Sung-Il; Kim, Jeongtae; Koo, Chiwan; Joung, Yeun-Ho; Choi, Jiyeon

2018-02-01

Microfluidics technology which deals with small liquid samples and reagents within micro-scale channels has been widely applied in various aspects of biological, chemical, and life-scientific research. For fabricating microfluidic devices, a silicon-based polymer, PDMS (Polydimethylsiloxane), is widely used in soft lithography, but it has several drawbacks for microfluidic applications. Glass has many advantages over PDMS due to its excellent optical, chemical, and mechanical properties. However, difficulties in fabrication of glass microfluidic devices that requires multiple skilled steps such as MEMS technology taking several hours to days, impedes broad application of glass based devices. Here, we demonstrate a rapid and optical prototyping of a glass microfluidic device by using femtosecond laser assisted selective etching (LASE) and femtosecond laser welding. A microfluidic droplet generator was fabricated as a demonstration of a microfluidic device using our proposed prototyping. The fabrication time of a single glass chip containing few centimeter long and complex-shaped microfluidic channels was drastically reduced in an hour with the proposed laser based rapid and simple glass micromachining and hermetic packaging technique.

Self-driven filter-based blood plasma separator microfluidic chip for point-of-care testing

International Nuclear Information System (INIS)

Madadi, Hojjat; Casals-Terré, Jasmina; Mohammadi, Mahdi

2015-01-01

There is currently a growing need for lab-on-a-chip devices for use in clinical analysis and diagnostics, especially in the area of patient care. The first step in most blood assays is plasma extraction from whole blood. This paper presents a novel, self-driven blood plasma separation microfluidic chip, which can extract more than 0.1 μl plasma from a single droplet of undiluted fresh human blood (∼5 μl). This volume of blood plasma is extracted from whole blood with high purity (more than 98%) in a reasonable time frame (3 to 5 min), and without the need for any external force. This would be the first step towards the realization of a single-use, self-blood test that does not require any external force or power source to deliver and analyze a fresh whole-blood sample, in contrast to the existing time-consuming conventional blood analysis. The prototypes are manufactured in polydimethylsiloxane that has been modified with a strong nonionic surfactant (Silwet L-77) to achieve hydrophilic behavior. The main advantage of this microfluidic chip design is the clogging delay in the filtration area, which results in an increased amount of extracted plasma (0.1 μl). Moreover, the plasma can be collected in one or more 10 μm-deep channels to facilitate the detection and readout of multiple blood assays. This high volume of extracted plasma is achieved thanks to a novel design that combines maximum pumping efficiency without disturbing the red blood cells’ trajectory through the use of different hydrodynamic principles, such as a constriction effect and a symmetrical filtration mode. To demonstrate the microfluidic chip’s functionality, we designed and fabricated a novel hybrid microdevice that exhibits the benefits of both microfluidics and lateral flow immunochromatographic tests. The performance of the presented hybrid microdevice is validated using rapid detection of thyroid stimulating hormone within a single droplet of whole blood. (paper)

Transfection in perfused microfluidic cell culture devices: A case study.

Science.gov (United States)

Raimes, William; Rubi, Mathieu; Super, Alexandre; Marques, Marco P C; Veraitch, Farlan; Szita, Nicolas

2017-08-01

Automated microfluidic devices are a promising route towards a point-of-care autologous cell therapy. The initial steps of induced pluripotent stem cell (iPSC) derivation involve transfection and long term cell culture. Integration of these steps would help reduce the cost and footprint of micro-scale devices with applications in cell reprogramming or gene correction. Current examples of transfection integration focus on maximising efficiency rather than viable long-term culture. Here we look for whole process compatibility by integrating automated transfection with a perfused microfluidic device designed for homogeneous culture conditions. The injection process was characterised using fluorescein to establish a LabVIEW-based routine for user-defined automation. Proof-of-concept is demonstrated by chemically transfecting a GFP plasmid into mouse embryonic stem cells (mESCs). Cells transfected in the device showed an improvement in efficiency (34%, n = 3) compared with standard protocols (17.2%, n = 3). This represents a first step towards microfluidic processing systems for cell reprogramming or gene therapy.

Integrated electrofluidic circuits: pressure sensing with analog and digital operation functionalities for microfluidics.

Science.gov (United States)

Wu, Chueh-Yu; Lu, Jau-Ching; Liu, Man-Chi; Tung, Yi-Chung

2012-10-21

Microfluidic technology plays an essential role in various lab on a chip devices due to its desired advantages. An automated microfluidic system integrated with actuators and sensors can further achieve better controllability. A number of microfluidic actuation schemes have been well developed. In contrast, most of the existing sensing methods still heavily rely on optical observations and external transducers, which have drawbacks including: costly instrumentation, professional operation, tedious interfacing, and difficulties of scaling up and further signal processing. This paper reports the concept of electrofluidic circuits - electrical circuits which are constructed using ionic liquid (IL)-filled fluidic channels. The developed electrofluidic circuits can be fabricated using a well-developed multi-layer soft lithography (MSL) process with polydimethylsiloxane (PDMS) microfluidic channels. Electrofluidic circuits allow seamless integration of pressure sensors with analog and digital operation functions into microfluidic systems and provide electrical readouts for further signal processing. In the experiments, the analog operation device is constructed based on electrofluidic Wheatstone bridge circuits with electrical outputs of the addition and subtraction results of the applied pressures. The digital operation (AND, OR, and XOR) devices are constructed using the electrofluidic pressure controlled switches, and output electrical signals of digital operations of the applied pressures. The experimental results demonstrate the designed functions for analog and digital operations of applied pressures are successfully achieved using the developed electrofluidic circuits, making them promising to develop integrated microfluidic systems with capabilities of precise pressure monitoring and further feedback control for advanced lab on a chip applications.

Detachably assembled microfluidic device for perfusion culture and post-culture analysis of a spheroid array.

Science.gov (United States)

Sakai, Yusuke; Hattori, Koji; Yanagawa, Fumiki; Sugiura, Shinji; Kanamori, Toshiyuki; Nakazawa, Kohji

2014-07-01

Microfluidic devices permit perfusion culture of three-dimensional (3D) tissue, mimicking the flow of blood in vascularized 3D tissue in our body. Here, we report a microfluidic device composed of a two-part microfluidic chamber chip and multi-microwell array chip able to be disassembled at the culture endpoint. Within the microfluidic chamber, an array of 3D tissue aggregates (spheroids) can be formed and cultured under perfusion. Subsequently, detailed post-culture analysis of the spheroids collected from the disassembled device can be performed. This device facilitates uniform spheroid formation, growth analysis in a high-throughput format, controlled proliferation via perfusion flow rate, and post-culture analysis of spheroids. We used the device to culture spheroids of human hepatocellular carcinoma (HepG2) cells under two controlled perfusion flow rates. HepG2 spheroids exhibited greater cell growth at higher perfusion flow rates than at lower perfusion flow rates, and exhibited different metabolic activity and mRNA and protein expression under the different flow rate conditions. These results show the potential of perfusion culture to precisely control the culture environment in microfluidic devices. The construction of spheroid array chambers allows multiple culture conditions to be tested simultaneously, with potential applications in toxicity and drug screening. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A single-walled carbon nanotube thin film-based pH-sensing microfluidic chip.

Science.gov (United States)

Li, Cheng Ai; Han, Kwi Nam; Pham, Xuan-Hung; Seong, Gi Hun

2014-04-21

A novel microfluidic pH-sensing chip was developed based on pH-sensitive single-walled carbon nanotubes (SWCNTs). In this study, the SWCNT thin film acted both as an electrode and a pH-sensitive membrane. The potentiometric pH response was observed by electronic structure changes in the semiconducting SWCNTs in response to the pH level. In a microfluidic chip consisting of a SWCNT pH-sensing working electrode and an Ag/AgCl reference electrode, the calibration plot exhibited promising pH-sensing performance with an ideal Nernstian response of 59.71 mV pH(-1) between pH 3 and 11 (standard deviation of the sensitivity is 1.5 mV pH(-1), R(2) = 0.985). Moreover, the SWCNT electrode in the microfluidic device showed no significant variation at any pH value in the range of the flow rate between 0.1 and 15 μl min(-1). The selectivity coefficients of the SWCNT electrode revealed good selectivity against common interfering ions.

One-step fabrication of microfluidic chips with in-plane, adhesive-free interconnections

International Nuclear Information System (INIS)

Sabourin, D; Dufva, M; Jensen, T; Kutter, J; Snakenborg, D

2010-01-01

A simple method for creating interconnections to a common microfluidic device material, poly(methyl methacrylate) (PMMA), is presented. A press-fit interconnection is created between oversized, deformable tubing and complementary, undersized semi-circular ports fabricated into PMMA bonding surfaces by direct micromilling. Upon UV-assisted bonding the tubing is trapped in the ports of the PMMA chip and forms an integrated, in-plane and adhesive-free interconnection. The interconnections support the average pressure of 6.1 bar and can be made with small dead volumes. A comparison is made to a similar interconnection approach which uses tubing to act as a gasket between a needle and port on the microfluidic chip. (technical note)

Silk-microfluidics for advanced biotechnological applications: A progressive review.

Science.gov (United States)

Konwarh, Rocktotpal; Gupta, Prerak; Mandal, Biman B

2016-01-01

Silk based biomaterials have not only carved a unique niche in the domain of regenerative medicine but new avenues are also being explored for lab-on-a-chip applications. It is pertinent to note that biospinning of silk represents nature's signature microfluidic-maneuver. Elucidation of non-Newtonian flow of silk in the glands of spiders and silkworms has inspired researchers to fabricate devices for continuous extrusion and concentration of silk. Microfluidic channel networks within porous silk scaffolds ensure optimal nutrient and oxygen supply apart from serving as precursors for vascularization in tissue engineering applications. On the other hand, unique topographical features and surface wettability of natural silk fibers have inspired development of a number of simple and cost-effective devices for applications like blood typing and chemical sensing. This review mirrors the recent progress and challenges in the domain of silk-microfluidics for prospective avant-garde applications in the realm of biotechnology. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimizing Polymer Lab-on-Chip Platforms for Ultrasonic Manipulation: Influence of the Substrate

Directory of Open Access Journals (Sweden)

Itziar González

2015-05-01

Full Text Available The choice of substrate material in a chip that combines ultrasound with microfluidics for handling biological and synthetic microparticles can have a profound effect on the performance of the device. This is due to the high surface-to-volume ratio that exists within such small structures and acquires particular relevance in polymer-based resonators with 3D standing waves. This paper presents three chips developed to perform particle flow-through separation by ultrasound based on a polymeric SU-8 layer containing channelization over three different substrates: Polymethyl methacrylate (PMMA; Pyrex; and a cracked PMMA composite-like structure. Through direct observations of polystyrene microbeads inside the channel, the three checked chips exhibit their potential as disposable continuous concentration devices with different spatial pressure patterns at frequencies of resonance close to 1 Mhz. Chips with Pyrex and cracked PMMA substrates show restrictions on the number of pressure nodes established in the channel associated with the inhibition of 3D modes in the solid structure. The glass-substrate chip presents some advantages associated with lower energy requirements to collect particles. According to the results, the use of polymer-based chips with rigid substrates can be advantageous for applications that require short treatment times (clinical tests handling human samples and low-cost fabrication.

Magnetic Tools for Lab-on-a-chip Technologies

Energy Technology Data Exchange (ETDEWEB)

Pekas, Nikola Slobodan [Iowa State Univ., Ames, IA (United States)

2006-01-01

This study establishes a set of magnetics-based tools that have been integrated with microfluidic systems. The overall impact of the work begins to enable the rapid and efficient manipulation and detection of magnetic entities such as particles, picoliter-sized droplets, or bacterial cells. Details of design, fabrication, and theoretical and experimental assessments are presented. The manipulation strategy has been demonstrated in the format of a particle diverter, whereby micron-sized particles are actively directed into desired flow channels at a split-flow junction by means of integrated microelectromagnets. Magnetic detection has been realized by deploying Giant Magnetoresistance (GMR) sensors--microfabricated structures originally developed for use as readout elements in computer hard-drives. We successfully transferred the GMR technology to the lab-on-a-chip arena, and demonstrated the versatility of the concept in several important areas: real-time, integrated monitoring of the properties of multiphase droplet flows; rapid quantitative determination of the concentration of magnetic nanoparticles in droplets of ferrofluids; and high-speed detection of individual magnetic microparticles and magnetotactic bacteria. The study also includes novel schemes for hydrodynamic flow focusing that work in conjunction with GMR-based detection to ensure precise navigation of the sample stream through the GMR detection volume, therefore effectively establishing a novel concept of a microfabricated magnetic flow cytometer.

Piezoresistive microcantilever based lab-on-a-chip system for detection of macronutrients in the soil

Science.gov (United States)

Patkar, Rajul S.; Ashwin, Mamta; Rao, V. Ramgopal

2017-12-01

Monitoring of soil nutrients is very important in precision agriculture. In this paper, we have demonstrated a micro electro mechanical system based lab-on-a-chip system for detection of various soil macronutrients which are available in ionic form K+, NO3-, and H2PO4-. These sensors are highly sensitive piezoresistive silicon microcantilevers coated with a polymer matrix containing methyltridodecylammonium nitrate ionophore/ nitrate ionophore VI for nitrate sensing, 18-crown-6 ether for potassium sensing and Tributyltin chloride for phosphate detection. A complete lab-on-a-chip system integrating a highly sensitive current excited Wheatstone's bridge based portable electronic setup along with arrays of microcantilever devices mounted on a printed circuit board with a liquid flow cell for on the site experimentation for soil test has been demonstrated.

Plastic lab-on-a-chip for fluorescence excitation with integrated organic semiconductor lasers.

Science.gov (United States)

Vannahme, Christoph; Klinkhammer, Sönke; Lemmer, Uli; Mappes, Timo

2011-04-25

Laser light excitation of fluorescent markers offers highly sensitive and specific analysis for bio-medical or chemical analysis. To profit from these advantages for applications in the field or at the point-of-care, a plastic lab-on-a-chip with integrated organic semiconductor lasers is presented here. First order distributed feedback lasers based on the organic semiconductor tris(8-hydroxyquinoline) aluminum (Alq3) doped with the laser dye 4-dicyanomethylene-2-methyl-6-(p-dimethylaminostyril)-4H-pyrane (DCM), deep ultraviolet induced waveguides, and a nanostructured microfluidic channel are integrated into a poly(methyl methacrylate) (PMMA) substrate. A simple and parallel fabrication process is used comprising thermal imprint, DUV exposure, evaporation of the laser material, and sealing by thermal bonding. The excitation of two fluorescent marker model systems including labeled antibodies with light emitted by integrated lasers is demonstrated.

Smartphone technology can be transformative to the deployment of lab-on-chip diagnostics

Science.gov (United States)

Erickson, David; O’Dell, Dakota; Jiang, Li; Oncescu, Vlad; Gumus, Abdurrahman; Lee, Seoho; Mancuso, Matthew; Mehta, Saurabh

2014-01-01

The rapid expansion of mobile technology is transforming the biomedical landscape. By 2016 there will be 260M active smartphones in the US and millions of health accessories and software “apps” running off them. In parallel with this have come major technical achievements in lab-on-a-chip technology leading to incredible new biochemical sensors and molecular diagnostic devices. Despite these advancements, the uptake of lab-on-a-chip technologies at the consumer level has been somewhat limited. We believe that the widespread availability of smartphone technology and the capabilities they offer in terms of computation, communication, social networking, and imaging will be transformative to the deployment of lab-on-a-chip type technology both in the developed and developing world. In this paper we outline why we believe this is the case, the new business models that may emerge, and detail some specific application areas in which this synergy will have long term impact, namely: nutrition monitoring and disease diagnostics in limited resource settings. PMID:24700127

Acousto-plasmofluidics: Acoustic modulation of surface plasmon resonance in microfluidic systems

Directory of Open Access Journals (Sweden)

Daniel Ahmed

2015-09-01

Full Text Available We acoustically modulated the localized surface plasmon resonances (LSPRs of metal nanostructures integrated within microfluidic systems. An acoustically driven micromixing device based on bubble microstreaming quickly and homogeneously mixes multiple laminar flows of different refractive indices. The altered refractive index of the mixed fluids enables rapid modulation of the LSPRs of gold nanodisk arrays embedded within the microfluidic channel. The device features fast response for dynamic operation, and the refractive index within the channel is tailorable. With these unique features, our “acousto-plasmofluidic” device can be useful in applications such as optical switches, modulators, filters, biosensors, and lab-on-a-chip systems.

Cerenkov radiation imaging as a method for quantitative measurements of beta particles in a microfluidic chip

International Nuclear Information System (INIS)

Cho, Jennifer S; Taschereau, Richard; Olma, Sebastian; Liu Kan; Chen Yichun; Shen, Clifton K-F; Van Dam, R Michael; Chatziioannou, Arion F

2009-01-01

It has been observed that microfluidic chips used for synthesizing 18 F-labeled compounds demonstrate visible light emission without nearby scintillators or fluorescent materials. The origin of the light was investigated and found to be consistent with the emission characteristics from Cerenkov radiation. Since 18 F decays through the emission of high-energy positrons, the energy threshold for beta particles, i.e. electrons or positrons, to generate Cerenkov radiation was calculated for water and polydimethylsiloxane (PDMS), the most commonly used polymer-based material for microfluidic chips. Beta particles emitted from 18 F have a continuous energy spectrum, with a maximum energy that exceeds this energy threshold for both water and PDMS. In addition, the spectral characteristics of the emitted light from 18 F in distilled water were also measured, yielding a broad distribution from 300 nm to 700 nm, with higher intensity at shorter wavelengths. A photograph of the 18 F solution showed a bluish-white light emitted from the solution, further suggesting Cerenkov radiation. In this study, the feasibility of using this Cerenkov light emission as a method for quantitative measurements of the radioactivity within the microfluidic chip in situ was evaluated. A detector previously developed for imaging microfluidic platforms was used. The detector consisted of a charge-coupled device (CCD) optically coupled to a lens. The system spatial resolution, minimum detectable activity and dynamic range were evaluated. In addition, the calibration of a Cerenkov signal versus activity concentration in the microfluidic chip was determined. This novel method of Cerenkov radiation measurements will provide researchers with a simple yet robust quantitative imaging tool for microfluidic applications utilizing beta particles.

On-chip enucleation of an oocyte by untethered microrobots

International Nuclear Information System (INIS)

Ichikawa, Akihiko; Sakuma, Shinya; Sugita, Masakuni; Shoda, Tatsuro; Tamakoshi, Takahiro; Arai, Fumihito; Akagi, Satoshi

2014-01-01

We propose a novel on-chip enucleation of an oocyte with zona pellucida by using a combination of untethered microrobots. To achieve enucleation within the closed space of a microfluidic chip, two microrobots, a microknife and a microgripper were integrated into the microfluidic chip. These microrobots were actuated by an external magnetic force produced by permanent magnets placed on the robotic stage. The tip of the microknife was designed by considering the biological geometric feature of an oocyte, i.e. the oocyte has a polar body in maturation stage II. Moreover, the microknife was fabricated by using grayscale lithography, which allows fabrication of three-dimensional microstructures. The microgripper has a gripping function that is independent of the driving mechanism. On-chip enucleation was demonstrated, and the enucleated oocytes are spherical, indicating that the cell membrane of the oocytes remained intact. To confirm successful enucleation using this method, we investigated the viability of oocytes after enucleation. The results show that the production rate, i.e. the ratio between the number of oocytes that reach the blastocyst stage and the number of bovine oocytes after nucleus transfer, is 100%. The technique will contribute to complex cell manipulation such as cell surgery in lab-on-a-chip devices. (paper)

Graphene Oxide-Poly(dimethylsiloxane)-Based Lab-on-a-Chip Platform for Heavy-Metals Preconcentration and Electrochemical Detection.

Science.gov (United States)

Chałupniak, Andrzej; Merkoçi, Arben

2017-12-27

Herein, we present the application of a novel graphene oxide-poly(dimethylsiloxane) (GO-PDMS) composite in reversible adsorption/desorption, including detection of heavy metals. GO-PDMS was fabricated by simple blending of GO with silicon monomer in the presence of tetrahydrofuran, followed by polymerization initiated upon the addition of curing agent. We found GO concentration, curing agent concentration, pH, and contact time among the most important factors affecting the adsorption of Pb(II) used as a model heavy metal. The mechanism of adsorption is based on surface complexation, where oxygen active groups of negative charge can bind with bivalent metal ions Me(II). To demonstrate a practical application of this material, we fabricated microfluidic lab-on-a-chip platform for heavy-metals preconcentration and detection. This device consists of a screen-printed carbon electrode, a PDMS chip, and a GO-PDMS chip. The use of GO-PDMS preconcentration platform significantly improves the sensitivity of electrochemical detection of heavy metals (an increase of current up to 30× was observed), without the need of modifying electrodes or special reagents addition. Therefore, samples being so far below the limit of detection (0.5 ppb) were successfully detected. This approach is compatible also with real samples (seawater) as ionic strength was found as indifferent for the adsorption process. To the best of our knowledge, GO-PDMS was used for the first time in sensing application. Moreover, due to mechanical resistance and outstanding durability, it can be used multiple times unlike other GO-based platforms for heavy-metals adsorption.

Lab-on-a-Chip Systems for Biomedical and Environmental Monitoring

NARCIS (Netherlands)

Gardeniers, Johannes G.E.; van den Berg, Albert

2003-01-01

During the last decade, pocket-size analytical equipment based on the "lab-on-a-chip" approach has become available. These chips, in combination with portable electronic equipment, are applicable in e.g. "point-of-care" ion analysis of body fluids, forensics, identification of explosives, tracking

Lab-on-a-Chip systems for biomedical and environmental monitoring

NARCIS (Netherlands)

Gardeniers, Johannes G.E.; van den Berg, Albert

2004-01-01

During the last decade, pocket-sized analytical equipment based on the lab-on-a-chip approach has become available. These chips, in combination with portable electronic equipment, are applicable in, for example, point-of-care ion analysis of body fluids, forensics, identification of explosives,

On-chip real-time single-copy polymerase chain reaction in picoliter droplets

Energy Technology Data Exchange (ETDEWEB)

Beer, N R; Hindson, B; Wheeler, E; Hall, S B; Rose, K A; Kennedy, I; Colston, B

2007-04-20

The first lab-on-chip system for picoliter droplet generation and PCR amplification with real-time fluorescence detection has performed PCR in isolated droplets at volumes 10{sup 6} smaller than commercial real-time PCR systems. The system utilized a shearing T-junction in a silicon device to generate a stream of monodisperse picoliter droplets that were isolated from the microfluidic channel walls and each other by the oil phase carrier. An off-chip valving system stopped the droplets on-chip, allowing them to be thermal cycled through the PCR protocol without droplet motion. With this system a 10-pL droplet, encapsulating less than one copy of viral genomic DNA through Poisson statistics, showed real-time PCR amplification curves with a cycle threshold of {approx}18, twenty cycles earlier than commercial instruments. This combination of the established real-time PCR assay with digital microfluidics is ideal for isolating single-copy nucleic acids in a complex environment.

Digital Microfluidics Sample Analyzer

Science.gov (United States)

Pollack, Michael G.; Srinivasan, Vijay; Eckhardt, Allen; Paik, Philip Y.; Sudarsan, Arjun; Shenderov, Alex; Hua, Zhishan; Pamula, Vamsee K.

2010-01-01

Three innovations address the needs of the medical world with regard to microfluidic manipulation and testing of physiological samples in ways that can benefit point-of-care needs for patients such as premature infants, for which drawing of blood for continuous tests can be life-threatening in their own right, and for expedited results. A chip with sample injection elements, reservoirs (and waste), droplet formation structures, fluidic pathways, mixing areas, and optical detection sites, was fabricated to test the various components of the microfluidic platform, both individually and in integrated fashion. The droplet control system permits a user to control droplet microactuator system functions, such as droplet operations and detector operations. Also, the programming system allows a user to develop software routines for controlling droplet microactuator system functions, such as droplet operations and detector operations. A chip is incorporated into the system with a controller, a detector, input and output devices, and software. A novel filler fluid formulation is used for the transport of droplets with high protein concentrations. Novel assemblies for detection of photons from an on-chip droplet are present, as well as novel systems for conducting various assays, such as immunoassays and PCR (polymerase chain reaction). The lab-on-a-chip (a.k.a., lab-on-a-printed-circuit board) processes physiological samples and comprises a system for automated, multi-analyte measurements using sub-microliter samples of human serum. The invention also relates to a diagnostic chip and system including the chip that performs many of the routine operations of a central labbased chemistry analyzer, integrating, for example, colorimetric assays (e.g., for proteins), chemiluminescence/fluorescence assays (e.g., for enzymes, electrolytes, and gases), and/or conductometric assays (e.g., for hematocrit on plasma and whole blood) on a single chip platform.

Volume-of-fluid simulations in microfluidic T-junction devices: Influence of viscosity ratio on droplet size

Science.gov (United States)

Nekouei, Mehdi; Vanapalli, Siva A.

2017-03-01

We used volume-of-fluid (VOF) method to perform three-dimensional numerical simulations of droplet formation of Newtonian fluids in microfluidic T-junction devices. To evaluate the performance of the VOF method we examined the regimes of drop formation and determined droplet size as a function of system parameters. Comparison of the simulation results with four sets of experimental data from the literature showed good agreement, validating the VOF method. Motivated by the lack of adequate studies investigating the influence of viscosity ratio (λ) on the generated droplet size, we mapped the dependence of drop volume on capillary number (0.001 1. In addition, we find that at a given capillary number, the size of droplets does not vary appreciably when λ 1. We develop an analytical model for predicting the droplet size that includes a viscosity-dependent breakup time for the dispersed phase. This improved model successfully predicts the effects of the viscosity ratio observed in simulations. Results from this study are useful for the design of lab-on-chip technologies and manufacture of microfluidic emulsions, where there is a need to know how system parameters influence the droplet size.

Fabrication of a Microfluidic Device with Boron-doped Diamond Electrodes for Electrochemical Analysis

International Nuclear Information System (INIS)

Watanabe, Takeshi; Shibano, Shuhei; Maeda, Hideto; Sugitani, Ai; Katayama, Michinobu; Matsumoto, Yoshinori; Einaga, Yasuaki

2016-01-01

A prototype microfluidic device using boron-doped diamond (BDD) electrodes patterned on an alumina chip was designed and fabricated. Electrochemical microfluidic devices have advantages in that the amount of sample required is small, the measurement throughput is high, different functions can be integrated on a single device, and they are highly durable. In using the device for the flow injection analysis of oxalic acid, the application of a brief conditioning step ensured that the reproducibility of the current signal was excellent. Furthermore, the fabricated system also performed as a prototype of “elimination-detection flow system”, in which interfering species are eliminated using “elimination electrodes” prior to the species reaching the “detection electrode”. The fabricated device reduced the current due to interfering species by 78%. Designs of devices to improve this efficiency are also discussed.

Towards Multiplex Molecular Diagnosis—A Review of Microfluidic Genomics Technologies

Directory of Open Access Journals (Sweden)

Ismail Hussain Kamal Basha

2017-08-01

Full Text Available Highly sensitive and specific pathogen diagnosis is essential for correct and timely treatment of infectious diseases, especially virulent strains, in people. Point-of-care pathogen diagnosis can be a tremendous help in managing disease outbreaks as well as in routine healthcare settings. Infectious pathogens can be identified with high specificity using molecular methods. A plethora of microfluidic innovations in recent years have now made it increasingly feasible to develop portable, robust, accurate, and sensitive genomic diagnostic devices for deployment at the point of care. However, improving processing time, multiplexed detection, sensitivity and limit of detection, specificity, and ease of deployment in resource-limited settings are ongoing challenges. This review outlines recent techniques in microfluidic genomic diagnosis and devices with a focus on integrating them into a lab on a chip that will lead towards the development of multiplexed point-of-care devices of high sensitivity and specificity.

Rapid fabrication of microfluidic chips based on the simplest LED lithography

Science.gov (United States)

Li, Yue; Wu, Ping; Luo, Zhaofeng; Ren, Yuxuan; Liao, Meixiang; Feng, Lili; Li, Yuting; He, Liqun

2015-05-01

Microfluidic chips are generally fabricated by a soft lithography method employing commercial lithography equipment. These heavy machines require a critical room environment and high lamp power, and the cost remains too high for most normal laboratories. Here we present a novel microfluidics fabrication method utilizing a portable ultraviolet (UV) LED as an alternative UV source for photolithography. With this approach, we can repeat several common microchannels as do these conventional commercial exposure machines, and both the verticality of the channel sidewall and lithography resolution are proved to be acceptable. Further microfluidics applications such as mixing, blood typing and microdroplet generation are implemented to validate the practicability of the chips. This simple but innovative method decreases the cost and requirement of chip fabrication dramatically and may be more popular with ordinary laboratories.

Rapid fabrication of microfluidic chips based on the simplest LED lithography

International Nuclear Information System (INIS)

Li, Yue; Wu, Ping; Liao, Meixiang; Feng, Lili; Li, Yuting; He, Liqun; Luo, Zhaofeng; Ren, Yuxuan

2015-01-01

Microfluidic chips are generally fabricated by a soft lithography method employing commercial lithography equipment. These heavy machines require a critical room environment and high lamp power, and the cost remains too high for most normal laboratories. Here we present a novel microfluidics fabrication method utilizing a portable ultraviolet (UV) LED as an alternative UV source for photolithography. With this approach, we can repeat several common microchannels as do these conventional commercial exposure machines, and both the verticality of the channel sidewall and lithography resolution are proved to be acceptable. Further microfluidics applications such as mixing, blood typing and microdroplet generation are implemented to validate the practicability of the chips. This simple but innovative method decreases the cost and requirement of chip fabrication dramatically and may be more popular with ordinary laboratories. (paper)

A microfluidic microprocessor: controlling biomimetic containers and cells using hybrid integrated circuit/microfluidic chips.

Science.gov (United States)

Issadore, David; Franke, Thomas; Brown, Keith A; Westervelt, Robert M

2010-11-07

We present an integrated platform for performing biological and chemical experiments on a chip based on standard CMOS technology. We have developed a hybrid integrated circuit (IC)/microfluidic chip that can simultaneously control thousands of living cells and pL volumes of fluid, enabling a wide variety of chemical and biological tasks. Taking inspiration from cellular biology, phospholipid bilayer vesicles are used as robust picolitre containers for reagents on the chip. The hybrid chip can be programmed to trap, move, and porate individual living cells and vesicles and fuse and deform vesicles using electric fields. The IC spatially patterns electric fields in a microfluidic chamber using 128 × 256 (32,768) 11 × 11 μm(2) metal pixels, each of which can be individually driven with a radio frequency (RF) voltage. The chip's basic functions can be combined in series to perform complex biological and chemical tasks and can be performed in parallel on the chip's many pixels for high-throughput operations. The hybrid chip operates in two distinct modes, defined by the frequency of the RF voltage applied to the pixels: Voltages at MHz frequencies are used to trap, move, and deform objects using dielectrophoresis and voltages at frequencies below 1 kHz are used for electroporation and electrofusion. This work represents an important step towards miniaturizing the complex chemical and biological experiments used for diagnostics and research onto automated and inexpensive chips.

A Microfluidic Chip Based on Localized Surface Plasmon Resonance for Real-Time Monitoring of Antigen-Antibody Reactions

Science.gov (United States)

Hiep, Ha Minh; Nakayama, Tsuyoshi; Saito, Masato; Yamamura, Shohei; Takamura, Yuzuru; Tamiya, Eiichi

2008-02-01

Localized surface plasmon resonance (LSPR) connecting to noble metal nanoparticles is an important issue for many analytical and biological applications. Therefore, the development of microfluidic LSPR chip that allows studying biomolecular interactions becomes an essential requirement for micro total analysis systems (µTAS) integration. However, miniaturized process of the conventional surface plasmon resonance system has been faced with some limitations, especially with the usage of Kretschmann configuration in total internal reflection mode. In this study, we have tried to solve this problem by proposing a novel microfluidic LSPR chip operated with a simple collinear optical system. The poly(dimethylsiloxane) (PDMS) based microfluidic chip was fabricated by soft-lithography technique and enables to interrogate specific insulin and anti-insulin antibody reaction in real-time after immobilizing antibody on its surface. Moreover, the sensing ability of microfluidic LSPR chip was also evaluated with various glucose concentrations. The kinetic constant of insulin and anti-insulin antibody was determined and the detection limit of 100 ng/mL insulin was archived.

Interfacing microfluidic handling with spectroscopic detection for real-life applications via the lab-on-valve platform: A review

DEFF Research Database (Denmark)

Hansen, Elo Harald; Miró, Manuel

2008-01-01

with syringe pump propelling devices as a front end to a plethora of spectroscopic detection schemes including UV-Vis spectroscopy, spectrofluorimetry, chemiluminescence, AAS, AFS and ICP-AES/MS. In contrast to lab-on-a-chip units, the versatile configuration of the micromachined LOV readily facilitates...

Determination of aminoglycoside antibiotics using an on-chip microfluidic device with chemiluminescence detection

International Nuclear Information System (INIS)

Sierra-Rodero, M.; Fernandez-Romero, J.M.; Gomez-Hens, A.

2012-01-01

We describe an on-chip microflow injection (μFI) approach for the determination of aminoglycoside antibiotics using chemiluminescence (CL) detection. The method is based on the inhibition of the Cu(II)-catalyzed CL reaction of luminol and hydrogen peroxide by the aminoglycosides due to the formation of a complex between the antibiotic and Cu(II). The main features of the method include small sample volumes and a fast response. Syringe pumps were used to insert the sample and the reagents into the microfluidic device. CL was collected using a fiber optic bundle connected to a luminescence detector. All instrumental, hydrodynamic and chemical variables involved in the system were optimized using neomycin as the aminoglycoside model. Inhibition is proportional to the concentration of the antibiotics. The dynamic ranges of the calibration graphs obtained for neomycin, streptomycin and amikacin are 0.3-3.3, 0.9-13.7, and 0.8-8.5 μmol L -1 , and the detection limits are 0.09, 0.28 and 0.24 μmol L -1 , respectively. The precision of the methods, expressed as relative standard deviation, is in the range from 0.8 to 5.0 %. The method was successfully applied to the determination of neomycin in water samples, with recoveries ranging from 80 to 120 %. (author)

Fabrication of dielectrophoretic microfluidic chips using a facile screen-printing technique for microparticle trapping

International Nuclear Information System (INIS)

Wee, Wei Hong; Kadri, Nahrizul Adib; Pingguan-Murphy, Belinda; Li, Zedong; Hu, Jie; Xu, Feng; Li, Fei

2015-01-01

Trapping of microparticles finds wide applications in numerous fields. Microfluidic chips based on a dielectrophoresis (DEP) technique hold several advantages for trapping microparticles, such as fast result processing, a small amount of sample required, high spatial resolution, and high accuracy of target selection. There is an unmet need to develop DEP microfluidic chips on different substrates for different applications in a low cost, facile, and rapid way. This study develops a new facile method based on a screen-printing technique for fabrication of electrodes of DEP chips on three types of substrates (i.e. polymethyl-methacrylate (PMMA), poly(ethylene terephthalate) and A4 paper). The fabricated PMMA-based DEP microfluidic chip was selected as an example and successfully used to trap and align polystyrene microparticles in a suspension and cardiac fibroblasts in a cell culture solution. The developed electrode fabrication method is compatible with different kinds of DEP substrates, which could expand the future application field of DEP microfluidic chips, including new forms of point-of care diagnostics and trapping circulating tumor cells. (paper)

A microfluidic chip for electrochemical conversions in drug metabolism studies

NARCIS (Netherlands)

Odijk, Mathieu; Baumann, A.; Lohmann, W.; van den Brink, Floris Teunis Gerardus; Olthuis, Wouter; Karst, U.; van den Berg, Albert

2009-01-01

We have designed a microfluidic microreactor chip for electrochemical conversion of analytes, containing a palladium reference electrode and platinum working and counter electrodes. The counter electrode is placed in a separate side-channel on chip to prevent unwanted side-products appearing in the

SAXS on a chip: from dynamics of phase transitions to alignment phenomena at interfaces studied with microfluidic devices.

Science.gov (United States)

Silva, Bruno F B

2017-09-13

The field of microfluidics offers attractive possibilities to perform novel experiments that are difficult (or even impossible) to perform using conventional bulk and surface-based methods. Such attractiveness comes from several important aspects inherent to these miniaturized devices. First, the flow of fluids under submillimeter confinement typically leads to a drop of inertial forces, meaning that turbulence is practically suppressed. This leads to predictable and controllable flow profiles, along with well-defined chemical gradients and stress fields that can be used for controlled mixing and actuation on the micro and nanoscale. Secondly, intricate microfluidic device designs can be fabricated using cleanroom standard procedures. Such intricate geometries can take diverse forms, designed by researchers to perform complex tasks, that require exquisite control of flow of several components and gradients, or to mimic real world examples, facilitating the establishment of more realistic models. Thirdly, microfluidic devices are usually compatible with in situ or integrated characterization methods that allow constant real-time monitoring of the processes occurring inside the microchannels. This is very different from typical bulk-based methods, where usually one can only observe the final result, or otherwise, take quick snapshots of the evolving process or take aliquots to be analyzed separately. Altogether, these characteristics inherent to microfluidic devices provide researchers with a set of tools that allow not only exquisite control and manipulation of materials at the micro and nanoscale, but also observation of these effects. In this review, we will focus on the use and prospects of combining microfluidic devices with in situ small-angle X-ray scattering (and related techniques such as small-angle neutron scattering and X-ray photon correlation spectroscopy), and their enormous potential for physical-chemical research, mainly in self-assembly and phase

A microfluidic device for separation of amniotic fluid mesenchymal stem cells utilizing louver-array structures.

Science.gov (United States)

Wu, Huei-Wen; Lin, Xi-Zhang; Hwang, Shiaw-Min; Lee, Gwo-Bin

2009-12-01

Human mesenchymal stem cells can differentiate into multiple lineages for cell therapy and, therefore, have attracted considerable research interest recently. This study presents a new microfluidic device for bead and cell separation utilizing a combination of T-junction focusing and tilted louver-like structures. For the first time, a microfluidic device is used for continuous separation of amniotic stem cells from amniotic fluids. An experimental separation efficiency as high as 82.8% for amniotic fluid mesenchymal stem cells is achieved. Furthermore, a two-step separation process is performed to improve the separation efficiency to 97.1%. These results are based on characterization experiments that show that this microfluidic chip is capable of separating beads with diameters of 5, 10, 20, and 40 microm by adjusting the volume-flow-rate ratio between the flows in the main and side channels of the T-junction focusing structure. An optimal volume-flow-rate ratio of 0.5 can lead to high separation efficiencies of 87.8% and 85.7% for 5-microm and 10-microm beads, respectively, in a one-step separation process. The development of this microfluidic chip may be promising for future research into stem cells and for cell therapy.

Computational analysis of integrated biosensing and shear flow in a microfluidic vascular model

Science.gov (United States)

Wong, Jeremy F.; Young, Edmond W. K.; Simmons, Craig A.

2017-11-01

Fluid flow and flow-induced shear stress are critical components of the vascular microenvironment commonly studied using microfluidic cell culture models. Microfluidic vascular models mimicking the physiological microenvironment also offer great potential for incorporating on-chip biomolecular detection. In spite of this potential, however, there are few examples of such functionality. Detection of biomolecules released by cells under flow-induced shear stress is a significant challenge due to severe sample dilution caused by the fluid flow used to generate the shear stress, frequently to the extent where the analyte is no longer detectable. In this work, we developed a computational model of a vascular microfluidic cell culture model that integrates physiological shear flow and on-chip monitoring of cell-secreted factors. Applicable to multilayer device configurations, the computational model was applied to a bilayer configuration, which has been used in numerous cell culture applications including vascular models. Guidelines were established that allow cells to be subjected to a wide range of physiological shear stress while ensuring optimal rapid transport of analyte to the biosensor surface and minimized biosensor response times. These guidelines therefore enable the development of microfluidic vascular models that integrate cell-secreted factor detection while addressing flow constraints imposed by physiological shear stress. Ultimately, this work will result in the addition of valuable functionality to microfluidic cell culture models that further fulfill their potential as labs-on-chips.

Integrated microfluidic device for single-cell trapping and spectroscopy

KAUST Repository

Liberale, Carlo

2013-02-13

Optofluidic microsystems are key components towards lab-on-a-chip devices for manipulation and analysis of biological specimens. In particular, the integration of optical tweezers (OT) in these devices allows stable sample trapping, while making available mechanical, chemical and spectroscopic analyses.

Integrated microfluidic device for single-cell trapping and spectroscopy

KAUST Repository

Liberale, Carlo; Cojoc, G.; Bragheri, F.; Minzioni, P.; Perozziello, G.; La Rocca, R.; Ferrara, L.; Rajamanickam, V.; Di Fabrizio, Enzo M.; Cristiani, I.

2013-01-01

Optofluidic microsystems are key components towards lab-on-a-chip devices for manipulation and analysis of biological specimens. In particular, the integration of optical tweezers (OT) in these devices allows stable sample trapping, while making available mechanical, chemical and spectroscopic analyses.

Design of pressure-driven microfluidic networks using electric circuit analogy.

Science.gov (United States)

Oh, Kwang W; Lee, Kangsun; Ahn, Byungwook; Furlani, Edward P

2012-02-07

This article reviews the application of electric circuit methods for the analysis of pressure-driven microfluidic networks with an emphasis on concentration- and flow-dependent systems. The application of circuit methods to microfluidics is based on the analogous behaviour of hydraulic and electric circuits with correlations of pressure to voltage, volumetric flow rate to current, and hydraulic to electric resistance. Circuit analysis enables rapid predictions of pressure-driven laminar flow in microchannels and is very useful for designing complex microfluidic networks in advance of fabrication. This article provides a comprehensive overview of the physics of pressure-driven laminar flow, the formal analogy between electric and hydraulic circuits, applications of circuit theory to microfluidic network-based devices, recent development and applications of concentration- and flow-dependent microfluidic networks, and promising future applications. The lab-on-a-chip (LOC) and microfluidics community will gain insightful ideas and practical design strategies for developing unique microfluidic network-based devices to address a broad range of biological, chemical, pharmaceutical, and other scientific and technical challenges.

Sperm quality assessment via separation and sedimentation in a microfluidic device.

Science.gov (United States)

Chen, Chang-Yu; Chiang, Tsun-Chao; Lin, Cheng-Ming; Lin, Shu-Sheng; Jong, De-Shien; Tsai, Vincent F-S; Hsieh, Ju-Ton; Wo, Andrew M

2013-09-07

A major reason for infertility is due to male factors, including the quality of spermatozoa, which is a primary factor and often difficult to assess, particularly the total sperm concentration and its motile percentage. This work presents a simple microfluidic device to assess sperm quality by quantifying both total and motile sperm counts. The key design feature of the microfluidic device is two channels separated by a permeative phase-guide structure, where one channel is filled with raw semen and the other with pure buffer. The semen sample was allowed to reach equilibrium in both chambers, whereas non-motile sperms remained in the original channel, and roughly half of the motile sperms would swim across the phase-guide barrier into the buffer channel. Sperms in each channel agglomerated into pellets after centrifugation, with the corresponding area representing total and motile sperm concentrations. Total sperm concentration up to 10(8) sperms per ml and motile percentage in the range of 10-70% were tested, encompassing the cutoff value of 40% stated by World Health Organization standards. Results from patient samples show compact and robust pellets after centrifugation. Comparison of total sperm concentration between the microfluidic device and the Makler chamber reveal they agree within 5% and show strong correlation, with a coefficient of determination of R(2) = 0.97. Motile sperm count between the microfluidic device and the Makler chamber agrees within 5%, with a coefficient of determination of R(2) = 0.84. Comparison of results from the Makler Chamber, sperm quality analyzer, and the microfluidic device revealed that results from the microfluidic device agree well with the Makler chamber. The sperm microfluidic chip analyzes both total and motile sperm concentrations in one spin, is accurate and easy to use, and should enable sperm quality analysis with ease.

OLED Hybrid Integrated Polymer Microfluidic Biosensing for Point of Care Testing

Directory of Open Access Journals (Sweden)

Ashwin Acharya

2015-09-01

Full Text Available This paper reports a microfluidic platform with external hybrid integration of an organic light emitting diode (OLED as an excitation source. This device can be used as a simple and cost effective biosensing element. The device is capable of rapid in-situ detection of biological elements such as sensing of interaction of antigen with fluorescent tagged antibody conjugates. These portable microfluidic systems have great potential for use an OLED in a single chip with very high accuracy and sensitivity for various point-of-care (POC diagnosis and lab on a chip (LOC applications, as the miniaturization of the biosensor is essential for handling smaller sample volumes in order to achieve high throughput. The biosensing element was successfully tested to detect anti-sheep IgG conjugates tagged to Alexafluor using a fluorescence based immunoassay method.

On-Chip Fluorescence Switching System for Constructing a Rewritable Random Access Data Storage Device.

Science.gov (United States)

Nguyen, Hoang Hiep; Park, Jeho; Hwang, Seungwoo; Kwon, Oh Seok; Lee, Chang-Soo; Shin, Yong-Beom; Ha, Tai Hwan; Kim, Moonil

2018-01-10

We report the development of on-chip fluorescence switching system based on DNA strand displacement and DNA hybridization for the construction of a rewritable and randomly accessible data storage device. In this study, the feasibility and potential effectiveness of our proposed system was evaluated with a series of wet experiments involving 40 bits (5 bytes) of data encoding a 5-charactered text (KRIBB). Also, a flexible data rewriting function was achieved by converting fluorescence signals between "ON" and "OFF" through DNA strand displacement and hybridization events. In addition, the proposed system was successfully validated on a microfluidic chip which could further facilitate the encoding and decoding process of data. To the best of our knowledge, this is the first report on the use of DNA hybridization and DNA strand displacement in the field of data storage devices. Taken together, our results demonstrated that DNA-based fluorescence switching could be applicable to construct a rewritable and randomly accessible data storage device through controllable DNA manipulations.

Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip.

Science.gov (United States)

Godin, Jessica; Chen, Chun-Hao; Cho, Sung Hwan; Qiao, Wen; Tsai, Frank; Lo, Yu-Hwa

2008-10-01

Microfluidics and photonics come together to form a field commonly referred to as 'optofluidics'. Flow cytometry provides the field with a technology base from which both microfluidic and photonic components be developed and integrated into a useful device. This article reviews some of the more recent developments to familiarize a reader with the current state of the technologies and also highlights the requirements of the device and how researchers are working to meet these needs.

Fabrication of a microfluidic chip by UV bonding at room temperature for integration of temperature-sensitive layers

Science.gov (United States)

Schlautmann, S.; Besselink, G. A. J.; Radhakrishna Prabhu, G.; Schasfoort, R. B. M.

2003-07-01

A method for the bonding of a microfluidic device at room temperature is presented. The wafer with the fluidic structures was bonded to a sensor wafer with gold pads by means of adhesive bonding, utilizing an UV-curable glue layer. To avoid filling the fluidic channels with the glue, a stamping process was developed which allows the selective application of a thin glue layer. In this way a microfluidic glass chip was fabricated that could be used for performing surface plasmon resonance measurements without signs of leakage. The advantage of this method is the possibility of integration of organic layers as well as other temperature-sensitive layers into a microfluidic glass device.

Scalable Device for Automated Microbial Electroporation in a Digital Microfluidic Platform.

Science.gov (United States)

Madison, Andrew C; Royal, Matthew W; Vigneault, Frederic; Chen, Liji; Griffin, Peter B; Horowitz, Mark; Church, George M; Fair, Richard B

2017-09-15

Electrowetting-on-dielectric (EWD) digital microfluidic laboratory-on-a-chip platforms demonstrate excellent performance in automating labor-intensive protocols. When coupled with an on-chip electroporation capability, these systems hold promise for streamlining cumbersome processes such as multiplex automated genome engineering (MAGE). We integrated a single Ti:Au electroporation electrode into an otherwise standard parallel-plate EWD geometry to enable high-efficiency transformation of Escherichia coli with reporter plasmid DNA in a 200 nL droplet. Test devices exhibited robust operation with more than 10 transformation experiments performed per device without cross-contamination or failure. Despite intrinsic electric-field nonuniformity present in the EP/EWD device, the peak on-chip transformation efficiency was measured to be 8.6 ± 1.0 × 10 8 cfu·μg -1 for an average applied electric field strength of 2.25 ± 0.50 kV·mm -1 . Cell survival and transformation fractions at this electroporation pulse strength were found to be 1.5 ± 0.3 and 2.3 ± 0.1%, respectively. Our work expands the EWD toolkit to include on-chip microbial electroporation and opens the possibility of scaling advanced genome engineering methods, like MAGE, into the submicroliter regime.

Ultra-Sensitive Lab-on-a-Chip Detection of Sudan I in Food using Plasmonics-Enhanced Diatomaceous Thin Film.

Science.gov (United States)

Kong, Xianming; Squire, Kenny; Chong, Xinyuan; Wang, Alan X

2017-09-01

Sudan I is a carcinogenic compound containing an azo group that has been illegally utilized as an adulterant in food products to impart a bright red color to foods. In this paper, we develop a facile lab-on-a-chip device for instant, ultra-sensitive detection of Sudan I from real food samples using plasmonics-enhanced diatomaceous thin film, which can simultaneously perform on-chip separation using thin layer chromatography (TLC) and highly specific sensing using surface-enhanced Raman scattering (SERS) spectroscopy. Diatomite is a kind of nature-created photonic crystal biosilica with periodic pores and was used both as the stationary phase of the TLC plate and photonic crystals to enhance the SERS sensitivity. The on-chip chromatography capability of the TLC plate was verified by isolating Sudan I in a mixture solution containing Rhodamine 6G, while SERS sensing was achieved by spraying gold colloidal nanoparticles into the sensing spot. Such plasmonics-enhanced diatomaceous film can effectively detect Sudan I with more than 10 times improvement of the Raman signal intensity than commercial silica gel TLC plates. We applied this lab-on-a-chip device for real food samples and successfully detected Sudan I in chili sauce and chili oil down to 1 ppm, or 0.5 ng/spot. This on-chip TLC-SERS biosensor based on diatomite biosilica can function as a cost-effective, ultra-sensitive, and reliable technology for screening Sudan I and many other illicit ingredients to enhance food safety.

Microfluidic devices for sample preparation and rapid detection of foodborne pathogens.

Science.gov (United States)

Kant, Krishna; Shahbazi, Mohammad-Ali; Dave, Vivek Priy; Ngo, Tien Anh; Chidambara, Vinayaka Aaydha; Than, Linh Quyen; Bang, Dang Duong; Wolff, Anders

2018-03-10

Rapid detection of foodborne pathogens at an early stage is imperative for preventing the outbreak of foodborne diseases, known as serious threats to human health. Conventional bacterial culturing methods for foodborne pathogen detection are time consuming, laborious, and with poor pathogen diagnosis competences. This has prompted researchers to call the current status of detection approaches into question and leverage new technologies for superior pathogen sensing outcomes. Novel strategies mainly rely on incorporating all the steps from sample preparation to detection in miniaturized devices for online monitoring of pathogens with high accuracy and sensitivity in a time-saving and cost effective manner. Lab on chip is a blooming area in diagnosis, which exploits different mechanical and biological techniques to detect very low concentrations of pathogens in food samples. This is achieved through streamlining the sample handling and concentrating procedures, which will subsequently reduce human errors and enhance the accuracy of the sensing methods. Integration of sample preparation techniques into these devices can effectively minimize the impact of complex food matrix on pathogen diagnosis and improve the limit of detections. Integration of pathogen capturing bio-receptors on microfluidic devices is a crucial step, which can facilitate recognition abilities in harsh chemical and physical conditions, offering a great commercial benefit to the food-manufacturing sector. This article reviews recent advances in current state-of-the-art of sample preparation and concentration from food matrices with focus on bacterial capturing methods and sensing technologies, along with their advantages and limitations when integrated into microfluidic devices for online rapid detection of pathogens in foods and food production line. Copyright © 2018. Published by Elsevier Inc.

Digital Microfluidic System with Vertical Functionality

Directory of Open Access Journals (Sweden)

Brian F. Bender

2015-11-01

Full Text Available Digital (droplet microfluidics (DµF is a powerful platform for automated lab-on-a-chip procedures, ranging from quantitative bioassays such as RT-qPCR to complete mammalian cell culturing. The simple MEMS processing protocols typically employed to fabricate DµF devices limit their functionality to two dimensions, and hence constrain the applications for which these devices can be used. This paper describes the integration of vertical functionality into a DµF platform by stacking two planar digital microfluidic devices, altering the electrode fabrication process, and incorporating channels for reversibly translating droplets between layers. Vertical droplet movement was modeled to advance the device design, and three applications that were previously unachievable using a conventional format are demonstrated: (1 solutions of calcium dichloride and sodium alginate were vertically mixed to produce a hydrogel with a radially symmetric gradient in crosslink density; (2 a calcium alginate hydrogel was formed within the through-well to create a particle sieve for filtering suspensions passed from one layer to the next; and (3 a cell spheroid formed using an on-chip hanging-drop was retrieved for use in downstream processing. The general capability of vertically delivering droplets between multiple stacked levels represents a processing innovation that increases DµF functionality and has many potential applications.

Immuno-capture and in situ detection of Salmonella typhimurium on a novel microfluidic chip

Energy Technology Data Exchange (ETDEWEB)

Wang, Renjie, E-mail: 1058464972@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); Ni, Yanan, E-mail: 468885029@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); Xu, Yi, E-mail: xuyibbd@sina.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); National Center for International Research of Micro/Nano-System and New Material Technology, No. 174, St. Shazhengjie, Shapingba District, Chongqing (China); Key Laboratory of Fundamental Science of Micro/Nano-Device and System Technology for National Defense, Chongqing (China); Jiang, Yan, E-mail: 919865356@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); Dong, Chunyan, E-mail: 774176325@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); Chuan, Na, E-mail: 814859441@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China)

2015-01-01

Highlights: • A novel microfluidic chip and a LIF microsystem were designed and fabricated. • Salmonella typhimurium was captured and labeled by specific immuno-capture on chip. • CdSe/ZnS quantum dots-labeled bacteria were detected by in situ analysis using LIF microsystem. • The proposed method has potential application in practice. - Abstract: The new method presented in this article achieved the goal of capturing Salmonella typhimurium via immunoreaction and rapid in situ detection of the CdSe/ZnS quantum dots (QDs) labeled S. typhimurium by self-assembly light-emitting diode-induced fluorescence detection (LIF) microsystem on a specially designed multichannel microfluidic chip. CdSe/ZnS QDs were used as fluorescent markers improving detection sensitivity. The microfluidic chip developed in this study was composed of 12 sample channels, 3 mixing zones, and 6 immune reaction zones, which also acted as fluorescence detection zones. QDs–IgG–primary antibody complexes were generated by mixing CdSe/ZnS QDs conjugated secondary antibody (QDs–IgG) and S. typhimurium antibody (primary antibody) in mixing zones. Then, the complexes went into immune reaction zones to label previously captured S. typhimurium in the sandwich mode. The capture rate of S. typhimurium in each detection zone was up to 70%. The enriched QDs-labeled S. typhimurium was detected using a self-assembly LIF microsystem. A good linear relationship was obtained in the range from 3.7 × 10 to 3.7 × 10{sup 5} cfu mL{sup −1} using the equation I = 0.1739 log (C) − 0.1889 with R{sup 2} = 0.9907, and the detection limit was down to 37 cfu mL{sup −1}. The proposed method of online immunolabeling with QDs for in situ fluorescence detection on the designed multichannel microfluidic chip had been successfully used to detect S. typhimurium in pork sample, and it has shown potential advantages in practice.

Low-temperature, simple and fast integration technique of microfluidic chips by using a UV-curable adhesive

NARCIS (Netherlands)

Arayanarakool, Rerngchai; le Gac, Severine; van den Berg, Albert

2010-01-01

In the fields of MicroElectroMechanical Systems (MEMS) and Lab On a Chip (LOC), a device is often fabricated using diverse substrates which are processed separately and finally assembled together using a bonding process to yield the final device. Here we describe and demonstrate a novel

Novel developments in mobile sensing based on the integration of microfluidic devices and smartphones.

Science.gov (United States)

Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

2016-03-21

Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS(2)) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS(2) offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS(2) in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS(2) enables applications to remote in-field testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS(2) by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field.

Novel Developments of Mobile Sensing Based on the Integration of Microfluidic Devices and Smartphone

Science.gov (United States)

Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

2016-01-01

Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS2) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS2 offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS2 in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS2 enables applications to remote infield testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS2 by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field. PMID:26899264

A single microfluidic chip with dual surface properties for protein drug delivery.

Science.gov (United States)

Bokharaei, Mehrdad; Saatchi, Katayoun; Häfeli, Urs O

2017-04-15

Principles of double emulsion generation were incorporated in a glass microfluidic chip fabricated with two different surface properties in order to produce protein loaded polymer microspheres. The microspheres were produced by integrating two microfluidic flow focusing systems and a multi-step droplet splitting and mixing system into one chip. The chip consists of a hydrophobic and a hydrophilic section with two different heights, 12μm and 45μm, respectively. As a result, the protein is homogenously distributed throughout the polymer microsphere matrix, not just in its center (which has been studied before). In our work, the inner phase was bovine serum albumin (BSA) in phosphate buffered saline, the disperse phase was poly (lactic acid) in chloroform and the continuous phase was an aqueous solution of poly(vinyl alcohol). After solvent removal, BSA loaded microspheres with an encapsulation efficiency of up to 96% were obtained. Our results show the feasibility of producing microspheres loaded with a hydrophilic drug in a microfluidic system that integrates different microfluidic units into one chip. Copyright © 2017 Elsevier B.V. All rights reserved.

Selective in situ functionalization of biosensors on LOC devices using laminar co-flow

DEFF Research Database (Denmark)

Parra-Cabrera, C.; Sporer, C.; Rodriguez-Villareal, I.

2012-01-01

Many applications involving lab-on-a-chip (LOC) devices are prevented from entering the market because of difficulties to achieve mass production and impart suitable properties allowing long-term storage. To integrate biosensors on these microfluidic chips, one of the main restrictions...... is the fabrication and stability of the molecular modifications that must be performed on the surfaces of the sensors for a given application. The complexity of the problem increases exponentially when the LOC integrates several of these sensors. Here we present a system based on laminar co-flow to perform an on...

A simple and cost-effective method for fabrication of integrated electronic-microfluidic devices using a laser-patterned PDMS layer

KAUST Repository

Li, Ming

2011-12-03

We report a simple and cost-effective method for fabricating integrated electronic-microfluidic devices with multilayer configurations. A CO 2 laser plotter was employed to directly write patterns on a transferred polydimethylsiloxane (PDMS) layer, which served as both a bonding and a working layer. The integration of electronics in microfluidic devices was achieved by an alignment bonding of top and bottom electrode-patterned substrates fabricated with conventional lithography, sputtering and lift-off techniques. Processes of the developed fabrication method were illustrated. Major issues associated with this method as PDMS surface treatment and characterization, thickness-control of the transferred PDMS layer, and laser parameters optimization were discussed, along with the examination and testing of bonding with two representative materials (glass and silicon). The capability of this method was further demonstrated by fabricating a microfluidic chip with sputter-coated electrodes on the top and bottom substrates. The device functioning as a microparticle focusing and trapping chip was experimentally verified. It is confirmed that the proposed method has many advantages, including simple and fast fabrication process, low cost, easy integration of electronics, strong bonding strength, chemical and biological compatibility, etc. © Springer-Verlag 2011.

Fast Prototyping of Sensorized Cell Culture Chips and Microfluidic Systems with Ultrashort Laser Pulses

Directory of Open Access Journals (Sweden)

Sebastian M. Bonk

2015-03-01

Full Text Available We developed a confined microfluidic cell culture system with a bottom plate made of a microscopic slide with planar platinum sensors for the measurement of acidification, oxygen consumption, and cell adhesion. The slides were commercial slides with indium tin oxide (ITO plating or were prepared from platinum sputtering (100 nm onto a 10-nm titanium adhesion layer. Direct processing of the sensor structures (approximately three minutes per chip by an ultrashort pulse laser facilitated the production of the prototypes. pH-sensitive areas were produced by the sputtering of 60-nm Si3N4 through a simple mask made from a circuit board material. The system body and polydimethylsiloxane (PDMS molding forms for the microfluidic structures were manufactured by micromilling using a printed circuit board (PCB milling machine for circuit boards. The microfluidic structure was finally imprinted in PDMS. Our approach avoided the use of photolithographic techniques and enabled fast and cost-efficient prototyping of the systems. Alternatively, the direct production of metallic, ceramic or polymeric molding tools was tested. The use of ultrashort pulse lasers improved the precision of the structures and avoided any contact of the final structures with toxic chemicals and possible adverse effects for the cell culture in lab-on-a-chip systems.

Bioanalysis in microfluidic devices.

Science.gov (United States)

Khandurina, Julia; Guttman, András

2002-01-18

Microfabricated bioanalytical devices (also referred to as laboratory-on-a-chip or micro-TAS) offer highly efficient platforms for simultaneous analysis of a large number of biologically important molecules, possessing great potential for genome, proteome and metabolome studies. Development and implementation of microfluidic-based bioanalytical tools involves both established and evolving technologies, including microlithography, micromachining, micro-electromechanical systems technology and nanotechnology. This article provides an overview of the latest developments in the key device subject areas and the basic interdisciplinary technologies. Important aspects of DNA and protein analysis, interfacing issues and system integration are all thoroughly discussed, along with applications for this novel "synergized" technology in high-throughput separations of biologically important molecules. This review also gives a better understanding of how to utilize these technologies as well as to provide appropriate technical solutions to problems perceived as being more fundamental.

Chemiluminescence generation and detection in a capillary-driven microfluidic chip

Science.gov (United States)

Ramon, Charlotte; Temiz, Yuksel; Delamarche, Emmanuel

2017-02-01

The use of microfluidic technology represents a strong opportunity for providing sensitive, low-cost and rapid diagnosis at the point-of-care and such a technology might therefore support better, faster and more efficient diagnosis and treatment of patients at home and in healthcare settings both in developed and developing countries. In this work, we consider luminescence-based assays as an alternative to well-established fluorescence-based systems because luminescence does not require a light source or expensive optical components and is therefore a promising detection method for point-of-care applications. Here, we show a proof-of-concept of chemiluminescence (CL) generation and detection in a capillary-driven microfluidic chip for potential immunoassay applications. We employed a commercial acridan-based reaction, which is catalyzed by horseradish peroxidase (HRP). We investigated CL generation under flow conditions using a simplified immunoassay model where HRP is used instead of the complete sandwich immunocomplex. First, CL signals were generated in a capillary microfluidic chip by immobilizing HRP on a polydimethylsiloxane (PDMS) sealing layer using stencil deposition and flowing CL substrate through the hydrophilic channels. CL signals were detected using a compact (only 5×5×2.5 cm3) and custom-designed scanner, which was assembled for less than $30 and comprised a 128×1 photodiode array, a mini stepper motor, an Arduino microcontroller, and a 3D-printed housing. In addition, microfluidic chips having specific 30-μm-deep structures were fabricated and used to immobilize ensembles of 4.50 μm beads functionalized with HRP so as to generate high CL signals from capillary-driven chips.

Cytotoxicity of cadmium-containing quantum dots based on a study using a microfluidic chip

International Nuclear Information System (INIS)

Zheng Xiannuo; Weng Lixing; Tian Jing; Wang Lianhui; Wu Lei; Jin Qinghui; Zhao Jianlong

2012-01-01

There is a lack of reliable nanotoxicity assays available for monitoring and quantifying multiple cellular events in cultured cells. In this study, we used a microfluidic chip to systematically investigate the cytotoxicity of three kinds of well-characterized cadmium-containing quantum dots (QDs) with the same core but different shell structures, including CdTe core QDs, CdTe/CdS core–shell QDs, and CdTe/CdS/ZnS core–shell–shell QDs, in HEK293 cells. Using the microfluidic chip combined with fluorescence microscopy, multiple QD-induced cellular events including cell morphology, viability, proliferation, and QD uptake were simultaneously analysed. The three kinds of QDs showed significantly different cytotoxicities. The CdTe QDs, which are highly toxic to HEK293 cells, resulted in remarkable cellular and nuclear morphological changes, a dose-dependent decrease in cell viability, and strong inhibition of cell proliferation; the CdTe/CdS QDs were moderately toxic but did not significantly affect the proliferation of HEK293 cells; while the CdTe/CdS/ZnS QDs had no detectable influence on cytotoxicity with respect to cell morphology, viability, and proliferation. Our data indicated that QD cytotoxicity was closely related to their surface structures and specific physicochemical properties. This study also demonstrated that the microfluidic chip could serve as a powerful tool to systematically evaluate the cytotoxicity of nanoparticles in multiple cellular events. (paper)

Cytotoxicity of cadmium-containing quantum dots based on a study using a microfluidic chip

Science.gov (United States)

Zheng, Xiannuo; Tian, Jing; Weng, Lixing; Wu, Lei; Jin, Qinghui; Zhao, Jianlong; Wang, Lianhui

2012-02-01

There is a lack of reliable nanotoxicity assays available for monitoring and quantifying multiple cellular events in cultured cells. In this study, we used a microfluidic chip to systematically investigate the cytotoxicity of three kinds of well-characterized cadmium-containing quantum dots (QDs) with the same core but different shell structures, including CdTe core QDs, CdTe/CdS core-shell QDs, and CdTe/CdS/ZnS core-shell-shell QDs, in HEK293 cells. Using the microfluidic chip combined with fluorescence microscopy, multiple QD-induced cellular events including cell morphology, viability, proliferation, and QD uptake were simultaneously analysed. The three kinds of QDs showed significantly different cytotoxicities. The CdTe QDs, which are highly toxic to HEK293 cells, resulted in remarkable cellular and nuclear morphological changes, a dose-dependent decrease in cell viability, and strong inhibition of cell proliferation; the CdTe/CdS QDs were moderately toxic but did not significantly affect the proliferation of HEK293 cells; while the CdTe/CdS/ZnS QDs had no detectable influence on cytotoxicity with respect to cell morphology, viability, and proliferation. Our data indicated that QD cytotoxicity was closely related to their surface structures and specific physicochemical properties. This study also demonstrated that the microfluidic chip could serve as a powerful tool to systematically evaluate the cytotoxicity of nanoparticles in multiple cellular events.

Fabricating process of hollow out-of-plane Ni microneedle arrays and properties of the integrated microfluidic device

Science.gov (United States)

Zhu, Jun; Cao, Ying; Wang, Hong; Li, Yigui; Chen, Xiang; Chen, Di

2013-07-01

Although microfluidic devices that integrate microfluidic chips with hollow out-of-plane microneedle arrays have many advantages in transdermal drug delivery applications, difficulties exist in their fabrication due to the special three-dimensional structures of hollow out-of-plane microneedles. A new, cost-effective process for the fabrication of a hollow out-of-plane Ni microneedle array is presented. The integration of PDMS microchips with the Ni hollow microneedle array and the properties of microfluidic devices are also presented. The integrated microfluidic devices provide a new approach for transdermal drug delivery.

Prototyping chips in minutes: Direct Laser Plotting (DLP) of functional microfluidic structures

KAUST Repository

Wang, Limu

2013-10-10

We report a fast and simple prototyping method to fabricate polymer-based microfluidic chips using Direct Laser Plotting (DLP) technique, by which various functional micro-structures can be realized within minutes, in a mask-free and out-of-cleanroom fashion. A 2D Computer-Aid-Design (CAD) software was employed to layout the required micro-structures and micro-channels, a CO2 laser plotter was then used to construct the microstructures. The desired patterns can be plotted directly on PDMS substrates and bio-compatible polymer films by manipulating the strength and density of laser pulses. With the DLP technique, chip-embedded micro-electrodes, micro-mixers and 3D microfluidic chips with 5 layers, which normally require several days of work in a cleanroom facility, can be fabricated in minutes in common laboratory. This novel method can produce microfluidic channels with average feature size of 100 μm, while feature size of 50 μm or smaller is achievable by making use of the interference effect from laser impulsion. In this report, we present the optimized parameters for successful fabrication of 3D microchannels, micro-mixers and microfluidic chips for protein concentration measurements (Bovine Serum Albumine (BSA) test), and a novel procedure to pattern flexible embedding electrodes on PDMS-based microfluidic chips. DLP offers a convenient and low cost alternative to conventional microfluidic channel fabrication technique which relies on complicated and hazardous soft lithography process.

DNA extraction on bio-chip: history and preeminence over conventional and solid-phase extraction methods.

Science.gov (United States)

Ayoib, Adilah; Hashim, Uda; Gopinath, Subash C B; Md Arshad, M K

2017-11-01

This review covers a developmental progression on early to modern taxonomy at cellular level following the advent of electron microscopy and the advancement in deoxyribonucleic acid (DNA) extraction for expatiation of biological classification at DNA level. Here, we discuss the fundamental values of conventional chemical methods of DNA extraction using liquid/liquid extraction (LLE) followed by development of solid-phase extraction (SPE) methods, as well as recent advances in microfluidics device-based system for DNA extraction on-chip. We also discuss the importance of DNA extraction as well as the advantages over conventional chemical methods, and how Lab-on-a-Chip (LOC) system plays a crucial role for the future achievements.

Scheduling and Fluid Routing for Flow-Based Microfluidic Laboratories-on-a-Chip

DEFF Research Database (Denmark)

Minhass, Wajid Hassan; McDaniel, Jeffrey; Raagaard, Michael Lander

2017-01-01

Microfluidic laboratories-on-chip (LoCs) are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis onchip. There are several types of LoCs, each having its advantages and limitations. In this paper we are interested in flow-bas...

Development of a lab-on-chip electrochemical biosensor for water quality analysis based on microalgal photosynthesis.

Science.gov (United States)

Tsopela, A; Laborde, A; Salvagnac, L; Ventalon, V; Bedel-Pereira, E; Séguy, I; Temple-Boyer, P; Juneau, P; Izquierdo, R; Launay, J

2016-05-15

The present work was dedicated to the development of a lab-on-chip device for water toxicity analysis and more particularly herbicide detection in water. It consists in a portable system for on-site detection composed of three-electrode electrochemical microcells, integrated on a fluidic platform constructed on a glass substrate. The final goal is to yield a system that gives the possibility of conducting double, complementary detection: electrochemical and optical and therefore all materials used for the fabrication of the lab-on-chip platform were selected in order to obtain a device compatible with optical technology. The basic detection principle consisted in electrochemically monitoring disturbances in metabolic photosynthetic activities of algae induced by the presence of Diuron herbicide. Algal response, evaluated through oxygen (O2) monitoring through photosynthesis was different for each herbicide concentration in the examined sample. A concentration-dependent inhibition effect of the herbicide on photosynthesis was demonstrated. Herbicide detection was achieved through a range (blank - 1 µM Diuron herbicide solution) covering the limit of maximum acceptable concentration imposed by Canadian government (0.64 µM), using a halogen white light source for the stimulation of algal photosynthetic apparatus. Superior sensitivity results (limit of detection of around 0.1 µM) were obtained with an organic light emitting diode (OLED), having an emission spectrum adapted to algal absorption spectrum and assembled on the final system. Copyright © 2015 Elsevier B.V. All rights reserved.

Integrated Microfluidic Nucleic Acid Isolation, Isothermal Amplification, and Amplicon Quantification

Directory of Open Access Journals (Sweden)

Michael G. Mauk

2015-10-01

Full Text Available Microfluidic components and systems for rapid (<60 min, low-cost, convenient, field-deployable sequence-specific nucleic acid-based amplification tests (NAATs are described. A microfluidic point-of-care (POC diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of “lab on a chip” NAAT devices. A portable, miniaturized POC NAAT with performance comparable to conventional PCR (polymerase-chain reaction-based tests in clinical laboratories can be realized with a disposable, palm-sized, plastic microfluidic chip in which: (1 nucleic acids (NAs are extracted from relatively large (~mL volume sample lysates using an embedded porous silica glass fiber or cellulose binding phase (“membrane” to capture sample NAs in a flow-through, filtration mode; (2 NAs captured on the membrane are isothermally (~65 °C amplified; (3 amplicon production is monitored by real-time fluorescence detection, such as with a smartphone CCD camera serving as a low-cost detector; and (4 paraffin-encapsulated, lyophilized reagents for temperature-activated release are pre-stored in the chip. Limits of Detection (LOD better than 103 virons/sample can be achieved. A modified chip with conduits hosting a diffusion-mode amplification process provides a simple visual indicator to readily quantify sample NA template. In addition, a companion microfluidic device for extracting plasma from whole blood without a centrifuge, generating cell-free plasma for chip-based molecular diagnostics, is described. Extensions to a myriad of related applications including, for example, food testing, cancer screening, and insect genotyping are briefly surveyed.

On-chip gradient generation in 256 microfluidic cell cultures: simulation and experimental validation.

Science.gov (United States)

Somaweera, Himali; Haputhanthri, Shehan O; Ibraguimov, Akif; Pappas, Dimitri

2015-08-07

A microfluidic diffusion diluter was used to create a stable concentration gradient for dose response studies. The microfluidic diffusion diluter used in this study consisted of 128 culture chambers on each side of the main fluidic channel. A calibration method was used to find unknown concentrations with 12% error. Flow rate dependent studies showed that changing the flow rates generated different gradient patterns. Mathematical simulations using COMSOL Multi-physics were performed to validate the experimental data. The experimental data obtained for the flow rate studies agreed with the simulation results. Cells could be loaded into culture chambers using vacuum actuation and cultured for long times under low shear stress. Decreasing the size of the culture chambers resulted in faster gradient formation (20 min). Mass transport into the side channels of the microfluidic diffusion diluter used in this study is an important factor in creating the gradient using diffusional mixing as a function of the distance. To demonstrate the device's utility, an H2O2 gradient was generated while culturing Ramos cells. Cell viability was assayed in the 256 culture chambers, each at a discrete H2O2 concentration. As expected, the cell viability for the high concentration side channels increased (by injecting H2O2) whereas the cell viability in the low concentration side channels decreased along the chip due to diffusional mixing as a function of distance. COMSOL simulations were used to identify the effective concentration of H2O2 for cell viability in each side chamber at 45 min. The gradient effects were confirmed using traditional H2O2 culture experiments. Viability of cells in the microfluidic device under gradient conditions showed a linear relationship with the viability of the traditional culture experiment. Development of the microfluidic device used in this study could be used to study hundreds of concentrations of a compound in a single experiment.

Organ-Tumor-on-a-Chip for Chemosensitivity Assay: A Critical Review

Directory of Open Access Journals (Sweden)

Navid Kashaninejad

2016-07-01

Full Text Available With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1 Lung; (2 Bone marrow; (3 Brain; (4 Breast; (5 Urinary system (kidney, bladder and prostate; (6 Intestine; and (7 Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart–liver–intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET of

Investigation of the dye concentration influence on the lasing wavelength and threshold for a micro-fluidic dye laser

DEFF Research Database (Denmark)

Helbo, Bjarne; Kragh, Søren; Kjeldsen, B.G.

2003-01-01

We investigate a micro-fluidic dye laser, which can be integrated with polymer-based lab-on-a-chip microsystems without further processing steps. A simple rate-equation model is used to predict the lasing threshold. The laser device is characterised using the laser dye Rhodamine 6G dissolved...... in ethanol, and the influence of dye concentration on the lasing wavelength and threshold is investigated. The experiments confirm the predictions of the rate-equation model, that lasing can be achieved in the 10 mum long laser cavity with moderate concentrations of Rhodamine 6G in ethanol, starting from 5 x...

Polymer microfluidic device replacing fluids using only capillary force

Science.gov (United States)

Chung, Kwang Hyo; Lee, Dae Sik; Yang, Haesik; Kim, Sung Jin; Pyo, Hyun Bong

2005-02-01

A novel polymer microfluidic device for self-wash using only capillary force is presented. A liquid filled in a reaction chamber is replaced by another liquid with no external actuation. All the fluidic actuations in the device is pre-programmed about time and sequence, and accomplished by capillary force naturally. Careful design is necessary for exact actions. The fluidic conduits were designed by the newly derived theoretical equations about the capillary stop pressure and flow time. Simulations using CFD-ACE+ were conducted to check the validity of theory and the performance of the chip. These analytic results were consistent with experimental ones. The chip was made of polymers for the purpose of single use and low price. It was fabricated by sealing the hot-embossed PMMA substrate with a PET film. For simpler fabrication, the chip was of a single height. The embossing master was produced from a nickel-electroplating on a SU8-patterned Ni-plate followed by CMP. The contact angles of liquids on substrates were manipulated through the mixing of surfactants, and the temporal variations were monitored for a more exact design. The real actuation steps in experiment revealed the stable performance of selfwash, and coincided well with the designed ones. The presented microfluidic method can be applicable to other LOCs of special purposes through simple modification. For example, array or serial types would be possible for multiple selfwashes.

Real-time electrical impedimetric monitoring of blood coagulation process under temperature and hematocrit variations conducted in a microfluidic chip.

Directory of Open Access Journals (Sweden)

Kin Fong Lei

Full Text Available Blood coagulation is an extremely complicated and dynamic physiological process. Monitoring of blood coagulation is essential to predict the risk of hemorrhage and thrombosis during cardiac surgical procedures. In this study, a high throughput microfluidic chip has been developed for the investigation of the blood coagulation process under temperature and hematocrit variations. Electrical impedance of the whole blood was continuously recorded by on-chip electrodes in contact with the blood sample during coagulation. Analysis of the impedance change of the blood was conducted to investigate the characteristics of blood coagulation process and the starting time of blood coagulation was defined. The study of blood coagulation time under temperature and hematocrit variations was shown a good agreement with results in the previous clinical reports. The electrical impedance measurement for the definition of blood coagulation process provides a fast and easy measurement technique. The microfluidic chip was shown to be a sensitive and promising device for monitoring blood coagulation process even in a variety of conditions. It is found valuable for the development of point-of-care coagulation testing devices that utilizes whole blood sample in microliter quantity.

In search of low cost biological analysis: Wax or acrylic glue bonded paper microfluidic devices

KAUST Repository

Kodzius, Rimantas

2011-01-22

In this body of work we have been developing and characterizing paper based microfluidic fabrication technologies to produce low cost biological analysis. Specifically we investigated the performance of paper microfluidics that had been bonded using wax or acrylic glue, and characterized the affect of these and other microfluidic materials on the polymerase chain reaction (PCR). We report a simple, low-cost and detachable microfluidic chip incorporating easily accessible paper, glass slides or other polymer films as the chip materials along with adhesive wax or cyanoacrylate-based resin as the recycling bonding material. We use a laser to cut through the paper or film to form patterns and then sandwich the paper and film between glass sheets or polymer membranes. The hot-melt adhesive wax or simple cyanoacrylate-based resin can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate film, glass sheets, or metal plate. The wax bonding process is reversible and the wax is reusable through a melting and cooling process. With this process, a three-dimensional (3D) microfluidic chip is achievable by evacuating the channels of adhesive material in a hot-water. We applied the wax-paper based microfluidic chip to HeLa cell electroporation. Subsequently, a prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check the sealing ability and the durability of the chip, green fluorescence protein recombinant E. coli bacteria were cultured, with which the chemotaxis of E. coli was studied in order to determine the influence of antibiotic ciprofloxacin concentration on the E. coli migration. The chip bonded with cyanoacrylate-based resin was tested by measuring protein concentration and carrying out DNA capillary electrophoresis. To study the biocompatibility and applicability of our microfluidic chip fabrication technology, we tested the PCR compatibility of our chip materials along with various other common materials

A high-performance lab-on-a-chip liquid sensor employing surface acoustic wave resonance

Science.gov (United States)

Kustanovich, K.; Yantchev, V.; Kirejev, V.; Jeffries, G. D. M.; Lobovkina, T.; Jesorka, A.

2017-11-01

We demonstrate herein a new concept for lab-on-a-chip in-liquid sensing, through integration of surface acoustic wave resonance (SAR) in a one-port configuration with a soft polymer microfluidic delivery system. In this concept, the reflective gratings of a one-port surface acoustic wave (SAW) resonator are employed as mass loading-sensing elements, while the SAW transducer is protected from the measurement environment. We describe the design, fabrication, implementation, and characterization using liquid medium. The sensor operates at a frequency of 185 MHz and has demonstrated a comparable sensitivity to other SAW in-liquid sensors, while offering quality factor (Q) value in water of about 250, low impedance and fairly low susceptibility to viscous damping. For proof of principle, sensing performance was evaluated by means of binding 40 nm neutravidin-coated SiO2 nanoparticles to a biotin-labeled lipid bilayer deposited over the reflectors. Frequency shifts were determined for every step of the affinity assay. Demonstration of this integrated technology highlights the potential of SAR technology for in-liquid sensing.

A microfluidic device based on an evaporation-driven micropump

NARCIS (Netherlands)

Nie, C.; Frijns, A.J.H.; Mandamparambil, R.; Toonder, J.M.J. den

2015-01-01

In this paper we introduce a microfluidic device ultimately to be applied as a wearable sweat sensor. We show proof-of-principle of the microfluidic functions of the device, namely fluid collection and continuous fluid flow pumping. A filter-paper based layer, that eventually will form the interface

Review on recent and advanced applications of monoliths and related porous polymer gels in micro-fluidic devices

International Nuclear Information System (INIS)

Vazquez, Mercedes; Paull, Brett

2010-01-01

This review critically summarises recent novel and advanced achievements in the application of monolithic materials and related porous polymer gels in micro-fluidic devices appearing within the literature over the period of the last 5 years (2005-2010). The range of monolithic materials has developed rapidly over the past decade, with a diverse and highly versatile class of materials now available, with each exhibiting distinct porosities, pore sizes, and a wide variety of surface functionalities. A major advantage of these materials is their ease of preparation in micro-fluidic channels by in situ polymerisation, leading to monolithic materials being increasingly utilised for a larger variety of purposes in micro-fluidic platforms. Applications of porous polymer monoliths, silica-based monoliths and related homogeneous porous polymer gels in the preparation of separation columns, ion-permeable membranes, preconcentrators, extractors, electrospray emitters, micro-valves, electrokinetic pumps, micro-reactors and micro-mixers in micro-fluidic devices are discussed herein. Procedures used in the preparation of monolithic materials in micro-channels, as well as some practical aspects of the micro-fluidic chip fabrication are addressed. Recent analytical/bioanalytical and catalytic applications of the final micro-fluidic devices incorporating monolithic materials are also reviewed.

Screening applications in drug discovery based on microfluidic technology

Science.gov (United States)

Eribol, P.; Uguz, A. K.; Ulgen, K. O.

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

Screening applications in drug discovery based on microfluidic technology.

Science.gov (United States)

Eribol, P; Uguz, A K; Ulgen, K O

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

Real-time isothermal RNA amplification of toxic marine microalgae using preserved reagents on an integrated microfluidic platform.

Science.gov (United States)

Tsaloglou, Maria-Nefeli; Laouenan, Florian; Loukas, Christos-Moritz; Monsalve, Lisandro Gabriel; Thanner, Christine; Morgan, Hywel; Ruano-López, Jesus M; Mowlem, Matthew C

2013-01-21

Quantitation of specific RNA sequences is a useful technique in marine biology that can elucidate cell abundance, speciation and viability, especially for early detection of harmful algal blooms. We are thus developing an integrated microfluidic system for cell concentration and lysis, RNA extraction/purification and quantitative RNA detection for environmental applications. The portable system is based on a microfluidic cartridge, or "lab-card", using a low-cost injection moulded device, with a laminated lid. Here we present real-time isothermal RNA amplification using reagent master-mixes preserved on-chip in a gel at 4 °C for up to eight months. We demonstrate quantitation by reference to an internal control in a competitive assay with 500 cell equivalents of the toxic microalga Karenia brevis. Annealing of primers, amplification at 41 °C and real-time fluorescence detection of the internal control and target using sequence-specific molecular beacons were all performed on-chip.

Lab on a chip technologies for algae detection : a review

NARCIS (Netherlands)

Schaap, A.M.; Rohrlack, T.; Bellouard, Y.J.

2012-01-01

Over the last few decades, lab on a chip technologies have emerged as powerful tools for high-accuracy diagnosis with minute quantities of liquid and as tools for exploring cell properties in general. In this paper, we present a review of the current status of this technology in the context of algae

A smartphone controlled handheld microfluidic liquid handling system.

Science.gov (United States)

Li, Baichen; Li, Lin; Guan, Allan; Dong, Quan; Ruan, Kangcheng; Hu, Ronggui; Li, Zhenyu

2014-10-21

Microfluidics and lab-on-a-chip technologies have made it possible to manipulate small volume liquids with unprecedented resolution, automation and integration. However, most current microfluidic systems still rely on bulky off-chip infrastructures such as compressed pressure sources, syringe pumps and computers to achieve complex liquid manipulation functions. Here, we present a handheld automated microfluidic liquid handling system controlled by a smartphone, which is enabled by combining elastomeric on-chip valves and a compact pneumatic system. As a demonstration, we show that the system can automatically perform all the liquid handling steps of a bead-based HIV1 p24 sandwich immunoassay on a multi-layer PDMS chip without any human intervention. The footprint of the system is 6 × 10.5 × 16.5 cm, and the total weight is 829 g including battery. Powered by a 12.8 V 1500 mAh Li battery, the system consumed 2.2 W on average during the immunoassay and lasted for 8.7 h. This handheld microfluidic liquid handling platform is generally applicable to many biochemical and cell-based assays requiring complex liquid manipulation and sample preparation steps such as FISH, PCR, flow cytometry and nucleic acid sequencing. In particular, the integration of this technology with read-out biosensors may help enable the realization of the long-sought Tricorder-like handheld in vitro diagnostic (IVD) systems.

Simultaneous detection of multiple HPV DNA via bottom-well microfluidic chip within an infra-red PCR platform.

Science.gov (United States)

Liu, Wenjia; Warden, Antony; Sun, Jiahui; Shen, Guangxia; Ding, Xianting

2018-03-01

Portable Polymerase Chain Reaction (PCR) devices combined with microfluidic chips or lateral flow stripes have shown great potential in the field of point-of-need testing (PoNT) as they only require a small volume of patient sample and are capable of presenting results in a short time. However, the detection for multiple targets in this field leaves much to be desired. Herein, we introduce a novel PCR platform by integrating a bottom-well microfluidic chip with an infra-red (IR) excited temperature control method and fluorescence co-detection of three PCR products. Microfluidic chips are utilized to partition different samples into individual bottom-wells. The oil phase in the main channel contains multi-walled carbon nanotubes which were used as a heat transfer medium that absorbs energy from the IR-light-emitting diode (LED) and transfers heat to the water phase below. Cyclical rapid heating and cooling necessary for PCR are achieved by alternative power switching of the IR-LED and Universal Serial Bus (USB) mini-fan with a pulse width modulation scheme. This design of the IR-LED PCR platform is economic, compact, and fully portable, making it a promising application in the field of PoNT. The bottom-well microfluidic chip and IR-LED PCR platform were combined to fulfill a three-stage thermal cycling PCR for 40 cycles within 90 min for Human Papilloma Virus (HPV) detection. The PCR fluorescent signal was successfully captured at the end of each cycle. The technique introduced here has broad applications in nucleic acid amplification and PoNT devices.

Embedded Adaptive Optics for Ubiquitous Lab-on-a-Chip Readout on Intact Cell Phones

Directory of Open Access Journals (Sweden)

Pakorn Preechaburana

2012-06-01

Full Text Available The evaluation of disposable lab-on-a-chip (LOC devices on cell phones is an attractive alternative to migrate the analytical strength of LOC solutions to decentralized sensing applications. Imaging the micrometric detection areas of LOCs in contact with intact phone cameras is central to provide such capability. This work demonstrates a disposable and morphing liquid lens concept that can be integrated in LOC devices and refocuses micrometric features in the range necessary for LOC evaluation using diverse cell phone cameras. During natural evaporation, the lens focus varies adapting to different type of cameras. Standard software in the phone commands a time-lapse acquisition for best focal selection that is sufficient to capture and resolve, under ambient illumination, 50 μm features in regions larger than 500 × 500 μm². In this way, the present concept introduces a generic solution compatible with the use of diverse and unmodified cell phone cameras to evaluate disposable LOC devices.

Integrated sample-to-detection chip for nucleic acid test assays.

Science.gov (United States)

Prakash, R; Pabbaraju, K; Wong, S; Tellier, R; Kaler, K V I S

2016-06-01

Nucleic acid based diagnostic techniques are routinely used for the detection of infectious agents. Most of these assays rely on nucleic acid extraction platforms for the extraction and purification of nucleic acids and a separate real-time PCR platform for quantitative nucleic acid amplification tests (NATs). Several microfluidic lab on chip (LOC) technologies have been developed, where mechanical and chemical methods are used for the extraction and purification of nucleic acids. Microfluidic technologies have also been effectively utilized for chip based real-time PCR assays. However, there are few examples of microfluidic systems which have successfully integrated these two key processes. In this study, we have implemented an electro-actuation based LOC micro-device that leverages multi-frequency actuation of samples and reagents droplets for chip based nucleic acid extraction and real-time, reverse transcription (RT) PCR (qRT-PCR) amplification from clinical samples. Our prototype micro-device combines chemical lysis with electric field assisted isolation of nucleic acid in a four channel parallel processing scheme. Furthermore, a four channel parallel qRT-PCR amplification and detection assay is integrated to deliver the sample-to-detection NAT chip. The NAT chip combines dielectrophoresis and electrostatic/electrowetting actuation methods with resistive micro-heaters and temperature sensors to perform chip based integrated NATs. The two chip modules have been validated using different panels of clinical samples and their performance compared with standard platforms. This study has established that our integrated NAT chip system has a sensitivity and specificity comparable to that of the standard platforms while providing up to 10 fold reduction in sample/reagent volumes.

Microfluidic immunomagnetic separation for enhanced bacterial detection

DEFF Research Database (Denmark)

Hoyland, James; Kunstmann-Olsen, Casper; Ahmed, Shakil

A combined lab-on-a-chip approach combining immunomagnetic separation (IMS) and flow cytometry was developed for the enrichment and detection of salmonella contamination in food samples. Immunomagnetic beads were immobilized in chips consisting of long fractal meanders while contaminated samples...... to obtain maximum capturing efficiency. The effects of channel volume, path length and number of bends of microfluidic chip on IMS efficiency were also determined....

[Advances on enzymes and enzyme inhibitors research based on microfluidic devices].

Science.gov (United States)

Hou, Feng-Hua; Ye, Jian-Qing; Chen, Zuan-Guang; Cheng, Zhi-Yi

2010-06-01

With the continuous development in microfluidic fabrication technology, microfluidic analysis has evolved from a concept to one of research frontiers in last twenty years. The research of enzymes and enzyme inhibitors based on microfluidic devices has also made great progress. Microfluidic technology improved greatly the analytical performance of the research of enzymes and enzyme inhibitors by reducing the consumption of reagents, decreasing the analysis time, and developing automation. This review focuses on the development and classification of enzymes and enzyme inhibitors research based on microfluidic devices.

A microfluidic chip containing multiple 3D nanofibrous scaffolds for culturing human pluripotent stem cells

Science.gov (United States)

Wertheim, Lior; Shapira, Assaf; Amir, Roey J.; Dvir, Tal

2018-04-01

In microfluidics-based lab-on-a-chip systems, which are used for investigating the effect of drugs and growth factors on cells, the latter are usually cultured within the device’s channels in two-dimensional, and not in their optimal three-dimensional (3D) microenvironment. Herein, we address this shortfall by designing a microfluidic system, comprised of two layers. The upper layer of the system consists of multiple channels generating a gradient of soluble factors. The lower layer is comprised of multiple wells, each deposited with 3D, nanofibrous scaffold. We first used a mathematical model to characterize the fluid flow within the system. We then show that induced pluripotent stem cells can be seeded within the 3D scaffolds and be exposed to a well-mixed gradient of soluble factors. We believe that utilizing such system may enable in the future to identify new differentiation factors, investigate drug toxicity, and eventually allow to perform analyses on patient-specific tissues, in order to fit the appropriate combination and concentration of drugs.

Integration of Curved D-Type Optical Fiber Sensor with Microfluidic Chip.

Science.gov (United States)

Sun, Yung-Shin; Li, Chang-Jyun; Hsu, Jin-Cherng

2016-12-30

A curved D-type optical fiber sensor (OFS) combined with a microfluidic chip is proposed. This OFS, based on surface plasmon resonance (SPR) of the Kretchmann's configuration, is applied as a biosensor to measure the concentrations of different bio-liquids such as ethanol, methanol, and glucose solutions. The SPR phenomenon is attained by using the optical fiber to guide the light source to reach the side-polished, gold-coated region. Integrating this OFS with a polymethylmethacrylate (PMMA)-based microfluidic chip, the SPR spectra for liquids with different refractive indices are recorded. Experimentally, the sensitivity of the current biosensor was calculated to be in the order of 10 -5 RIU. This microfluidic chip-integrated OFS could be valuable for monitoring subtle changes in biological samples such as blood sugar, allergen, and biomolecular interactions.

High-throughput particle manipulation by hydrodynamic, electrokinetic, and dielectrophoretic effects in an integrated microfluidic chip

KAUST Repository

Li, Shunbo; Li, Ming; Bougot-Robin, Kristelle; Cao, Wenbin; Yeung Yeung Chau, Irene; Li, Weihua; Wen, Weijia

2013-01-01

Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.

High-throughput particle manipulation by hydrodynamic, electrokinetic, and dielectrophoretic effects in an integrated microfluidic chip

KAUST Repository

Li, Shunbo

2013-03-20

Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.

Cobalt hexacyanoferrate modified multi-walled carbon nanotubes/graphite composite electrode as electrochemical sensor on microfluidic chip

International Nuclear Information System (INIS)

Li Xinchun; Chen Zuanguang; Zhong Yuwen; Yang Fan; Pan Jianbin; Liang Yajing

2012-01-01

Highlights: ► CoHCF nanoparticles modified MWCNTs/graphite electrode use for electrochemistry on electrophoresis microchip for the first time. ► Simultaneous, rapid, and sensitive electrochemical detection of hydrazine and isoniazid in real samples. ► An exemplary work of CME sensor assembly onto microchip for determination of analytes with environmental significance. ► Manifestation of the applicability and flexibility of CME sensor for electroanalysis on microfluidic chip. - Abstract: Nanomaterial-based electrochemical sensor has received significant interest. In this work, cobalt hexacyanoferrate modified multi-walled carbon nanotubes/graphite composite electrode was electrochemically prepared and exploited as an amperometric detector for microchip electrophoresis. The prepared sensor displayed rapid and sensitive response towards hydrazine and isoniazid oxidation, which was attributed to synergetic electrocatalytic effect of cobalt hexacyanoferrate and multi-walled carbon nanotubes. The sensitivity enhancement with nearly two orders of magnitude was gained, compared with the bare carbon paste electrode, with the detection limit of 0.91 μM (S/N = 3) for hydrazine. Acceptable repeatability of the microanalysis system was verified by consecutive eleven injections of hydrazine without chip and electrode treatments, the RSDs for peak current and migration time were 3.4% and 2.1%, respectively. Meanwhile, well-shaped electrophoretic peaks were observed, mainly due to fast electron transfer of electroactive species on the modified electrode. The developed microchip-electrochemistry setup was successfully applied to the determination of hydrazine and isoniazid in river water and pharmaceutical preparation, respectively. Several merits of the novel electrochemical sensor coupled with microfluidic platform, such as comparative stability, easy fabrication and high sensitivity, hold great potential for hydrazine compounds assay in the lab-on-a-chip system.

Macromolecular Crystallization in Microfluidics for the International Space Station

Science.gov (United States)

Monaco, Lisa A.; Spearing, Scott

2003-01-01

At NASA's Marshall Space Flight Center, the Iterative Biological Crystallization (IBC) project has begun development on scientific hardware for macromolecular crystallization on the International Space Station (ISS). Currently ISS crystallization research is limited to solution recipes that were prepared on the ground prior to launch. The proposed hardware will conduct solution mixing and dispensing on board the ISS, be fully automated, and have imaging functions via remote commanding from the ground. Utilizing microfluidic technology, IBC will allow for on orbit iterations. The microfluidics LabChip(R) devices that have been developed, along with Caliper Technologies, will greatly benefit researchers by allowing for precise fluid handling of nano/pico liter sized volumes. IBC will maximize the amount of science return by utilizing the microfluidic approach and be a valuable tool to structural biologists investigating medically relevant projects.

Microfluidic Mixing Technology for a Universal Health Sensor

Science.gov (United States)

Chan, Eugene Y.; Bae, Candice

2009-01-01

A highly efficient means of microfluidic mixing has been created for use with the rHEALTH sensor an elliptical mixer and passive curvilinear mixing patterns. The rHEALTH sensor provides rapid, handheld, complete blood count, cell differential counts, electrolyte measurements, and other lab tests based on a reusable, flow-based microfluidic platform. These geometries allow for cleaning in a reusable manner, and also allow for complete mixing of fluid streams. The microfluidic mixing is performed by flowing two streams of fluid into an elliptical or curvilinear design that allows the combination of the flows into one channel. The mixing is accomplished by either chaotic advection around micro - fluidic loops. All components of the microfluidic chip are flow-through, meaning that cleaning solution can be introduced into the chip to flush out cells, plasma proteins, and dye. Tests were performed on multiple chip geometries to show that cleaning is efficient in any flowthrough design. The conclusion from these experiments is that the chip can indeed be flushed out with microliter volumes of solution and biological samples are cleaned readily from the chip with minimal effort. The technology can be applied in real-time health monitoring at patient s bedside or in a doctor s office, and real-time clinical intervention in acute situations. It also can be used for daily measurement of hematocrit for patients on anticoagulant drugs, or to detect acute myocardial damage outside a hospital.

Fast architecture-level synthesis of fault-tolerant flow-based microfluidic biochips

DEFF Research Database (Denmark)

Huang, Wei Lun; Gupta, Ankur; Roy, Sudip

2017-01-01

Microfluidic-based lab-on-a-chips have emerged as a popular technology for implementation of different biochemical test protocols used in medical diagnostics. However, in the manufacturing process or during operation of such chips, some faults may occur that leads to damage of the chip, which...

Utility of lab-on-a-chip technology for high-throughput nucleic acid and protein analysis

DEFF Research Database (Denmark)

Hawtin, Paul; Hardern, Ian; Wittig, Rainer

2005-01-01

On-chip electrophoresis can provide size separations of nucleic acids and proteins similar to more traditional slab gel electrophoresis. Lab-on-a-chip (LoaC) systems utilize on-chip electrophoresis in conjunction with sizing calibration, sensitive detection schemes, and sophisticated data analysi...

In search of low cost biological analysis: Wax or acrylic glue bonded paper microfluidic devices

KAUST Repository

Kodzius, Rimantas; Gong, Xiuqing; Li, Shunbo; Qin, Jianhua; Wen, Weijia; Wu, Jinbo; Xiao, Kang; Yi, Xin

2011-01-01

We report a simple, low-cost and detachable microfluidic chip incorporating easily accessible paper, glass slides or other polymer films as the chip materials along with adhesive wax or cyanoacrylate-based resin as the recycling bonding material. We use a laser to cut through the paper or film to form patterns and then sandwich the paper and film between glass sheets or polymer membranes. The hot-melt adhesive wax or simple cyanoacrylate-based resin can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate film, glass sheets, or metal plate. The wax bonding process is reversible and the wax is reusable through a melting and cooling process. With this process, a three-dimensional (3D) microfluidic chip is achievable by evacuating the channels of adhesive material in a hot-water. We applied the wax-paper based microfluidic chip to HeLa cell electroporation. Subsequently, a prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check the sealing ability and the durability of the chip, green fluorescence protein recombinant E. coli bacteria were cultured, with which the chemotaxis of E. coli was studied in order to determine the influence of antibiotic ciprofloxacin concentration on the E. coli migration. The chip bonded with cyanoacrylate-based resin was tested by measuring protein concentration and carrying out DNA capillary electrophoresis. To study the biocompatibility and applicability of our microfluidic chip fabrication technology, we tested the PCR compatibility of our chip materials along with various other common materials employed in the fabrication of microfluidic chips including: silicon, several kinds of silicon oxide, glasses, plastics, wax, and adhesives, etc. Two-temperature PCR was performed with these materials to determine their PCR-inhibitory effect. In most of the cases, addition of bovine serum albumin effectively improved the reaction yield. We also studied the individual PCR components

Lab-on-chip components for molecular detection

Science.gov (United States)

Adam, Tijjani; Dhahi, Th S.; Mohammed, Mohammed; Hashim, U.; Noriman, N. Z.; Dahham, Omar S.

2017-09-01

We successfully fabricated Lab on chip components and integrated for possible use in biomedical application. The sensor was fabricated by using conventional photolithography method integrated with PDMS micro channels for smooth delivery of sample to the sensing domain. The sensor was silanized and aminated with 3-Aminopropyl triethoxysilane (APTES) to functionalize the surface with biomolecules and create molecular binding chemistry. The resulting Si-O-Si- components were functionalized with oligonucleotides probe of HPV, which interacted with the single stranded HPV DNA target to create a field across on the device. The fabrication, immobilization and hybridization processes were characterized with current voltage (I-V) characterization (KEITHLEY, 6487). The sensor show selectivity for the HPV DNA target in a linear range from concentration 0.1 nM to 1 µM. This strategy presented a simple, rapid and sensitive platform for HPV detection and would become a powerful tool for pathogenic microorganisms screening in clinical diagnosis.

Experimental investigation of new manufacturing process chains to create micro-metal structures on polymer substrates for lab-on-chip sensors

DEFF Research Database (Denmark)

Calaon, Matteo; Islam, Aminul; Hansen, Hans Nørgaard

2012-01-01

Over the last two decades, lab-on-a-chip devices have emerged as a leading technology for life sciences, drug development, medical diagnostics, food safety, agricultural and environmental monitoring. The conventional methods used nowadays to manufacture these micro- and nano-functional surface...

Study of a Microfluidic Chip Integrating Single Cell Trap and 3D Stable Rotation Manipulation

Directory of Open Access Journals (Sweden)

Liang Huang

2016-08-01

Full Text Available Single cell manipulation technology has been widely applied in biological fields, such as cell injection/enucleation, cell physiological measurement, and cell imaging. Recently, a biochip platform with a novel configuration of electrodes for cell 3D rotation has been successfully developed by generating rotating electric fields. However, the rotation platform still has two major shortcomings that need to be improved. The primary problem is that there is no on-chip module to facilitate the placement of a single cell into the rotation chamber, which causes very low efficiency in experiment to manually pipette single 10-micron-scale cells into rotation position. Secondly, the cell in the chamber may suffer from unstable rotation, which includes gravity-induced sinking down to the chamber bottom or electric-force-induced on-plane movement. To solve the two problems, in this paper we propose a new microfluidic chip with manipulation capabilities of single cell trap and single cell 3D stable rotation, both on one chip. The new microfluidic chip consists of two parts. The top capture part is based on the least flow resistance principle and is used to capture a single cell and to transport it to the rotation chamber. The bottom rotation part is based on dielectrophoresis (DEP and is used to 3D rotate the single cell in the rotation chamber with enhanced stability. The two parts are aligned and bonded together to form closed channels for microfluidic handling. Using COMSOL simulation and preliminary experiments, we have verified, in principle, the concept of on-chip single cell traps and 3D stable rotation, and identified key parameters for chip structures, microfluidic handling, and electrode configurations. The work has laid a solid foundation for on-going chip fabrication and experiment validation.

Comparison of Ultrasonic Welding and Thermal Bonding for the Integration of Thin Film Metal Electrodes in Injection Molded Polymeric Lab-on-Chip Systems for Electrochemistry

Directory of Open Access Journals (Sweden)

Marco Matteucci

2016-10-01

Full Text Available We compare ultrasonic welding (UW and thermal bonding (TB for the integration of embedded thin-film gold electrodes for electrochemical applications in injection molded (IM microfluidic chips. The UW bonded chips showed a significantly superior electrochemical performance compared to the ones obtained using TB. Parameters such as metal thickness of electrodes, depth of electrode embedding, delivered power, and height of energy directors (for UW, as well as pressure and temperature (for TB, were systematically studied to evaluate the two bonding methods and requirements for optimal electrochemical performance. The presented technology is intended for easy and effective integration of polymeric Lab-on-Chip systems to encourage their use in research, commercialization and education.

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept

Directory of Open Access Journals (Sweden)

Adnane Kara

2016-05-01

Full Text Available In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 μ M was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an “intelligent” drug delivery system based on a feedback loop to monitor drug delivery.

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept.

Science.gov (United States)

Kara, Adnane; Rouillard, Camille; Mathault, Jessy; Boisvert, Martin; Tessier, Frédéric; Landari, Hamza; Melki, Imene; Laprise-Pelletier, Myriam; Boisselier, Elodie; Fortin, Marc-André; Boilard, Eric; Greener, Jesse; Miled, Amine

2016-05-28

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 μ M was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an "intelligent" drug delivery system based on a feedback loop to monitor drug delivery.

Integration of Curved D-Type Optical Fiber Sensor with Microfluidic Chip

Directory of Open Access Journals (Sweden)

Yung-Shin Sun

2016-12-01

Full Text Available A curved D-type optical fiber sensor (OFS combined with a microfluidic chip is proposed. This OFS, based on surface plasmon resonance (SPR of the Kretchmann’s configuration, is applied as a biosensor to measure the concentrations of different bio-liquids such as ethanol, methanol, and glucose solutions. The SPR phenomenon is attained by using the optical fiber to guide the light source to reach the side-polished, gold-coated region. Integrating this OFS with a polymethylmethacrylate (PMMA-based microfluidic chip, the SPR spectra for liquids with different refractive indices are recorded. Experimentally, the sensitivity of the current biosensor was calculated to be in the order of 10−5 RIU. This microfluidic chip-integrated OFS could be valuable for monitoring subtle changes in biological samples such as blood sugar, allergen, and biomolecular interactions.

Packaging of silicon sensors for microfluidic bio-analytical applications

International Nuclear Information System (INIS)

Wimberger-Friedl, Reinhold; Prins, Menno; Megens, Mischa; Dittmer, Wendy; Witz, Christiane de; Nellissen, Ton; Weekamp, Wim; Delft, Jan van; Ansems, Will; Iersel, Ben van

2009-01-01

A new industrial concept is presented for packaging biosensor chips in disposable microfluidic cartridges to enable medical diagnostic applications. The inorganic electronic substrates, such as silicon or glass, are integrated in a polymer package which provides the electrical and fluidic interconnections to the world and provides mechanical strength and protection for out-of-lab use. The demonstrated prototype consists of a molded interconnection device (MID), a silicon-based giant magneto-resistive (GMR) biosensor chip, a flex and a polymer fluidic part with integrated tubing. The various processes are compatible with mass manufacturing and run at a high yield. The devices show a reliable electrical interconnection between the sensor chip and readout electronics during extended wet operation. Sandwich immunoassays were carried out in the cartridges with surface functionalized sensor chips. Biological response curves were determined for different concentrations of parathyroid hormone (PTH) on the packaged biosensor, which demonstrates the functionality and biocompatibility of the devices. The new packaging concept provides a platform for easy further integration of electrical and fluidic functions, as for instance required for integrated molecular diagnostic devices in cost-effective mass manufacturing

Integration of Organic Light Emitting Diodes and Organic Photodetectors for Lab-on-a-Chip Bio-Detection Systems

Directory of Open Access Journals (Sweden)

Graeme Williams

2014-02-01

Full Text Available The rapid development of microfluidics and lab-on-a-chip (LoC technologies have allowed for the efficient separation and manipulation of various biomaterials, including many diagnostically relevant species. Organic electronics have similarly enjoyed a great deal of research, resulting in tiny, highly efficient, wavelength-selective organic light-emitting diodes (OLEDs and organic photodetectors (OPDs. We consider the blend of these technologies for rapid detection and diagnosis of biological species. In the ideal system, optically active or fluorescently labelled biological species can be probed via light emission from OLEDs, and their subsequent light emission can be detected with OPDs. The relatively low cost and simple fabrication of the organic electronic devices suggests the possibility of disposable test arrays. Further, with full integration, the finalized system can be miniaturized and made simple to use. In this review, we consider the design constraints of OLEDs and OPDs required to achieve fully organic electronic optical bio-detection systems. Current approaches to integrated LoC optical sensing are first discussed. Fully realized OLED- and OPD-specific photoluminescence detection systems from literature are then examined, with a specific focus on their ultimate limits of detection. The review highlights the enormous potential in OLEDs and OPDs for integrated optical sensing, and notes the key avenues of research for cheap and powerful LoC bio-detection systems.

A coral-on-a-chip microfluidic platform enabling live-imaging microscopy of reef-building corals

Science.gov (United States)

Shapiro, Orr H.; Kramarsky-Winter, Esti; Gavish, Assaf R.; Stocker, Roman; Vardi, Assaf

2016-01-01

Coral reefs, and the unique ecosystems they support, are facing severe threats by human activities and climate change. Our understanding of these threats is hampered by the lack of robust approaches for studying the micro-scale interactions between corals and their environment. Here we present an experimental platform, coral-on-a-chip, combining micropropagation and microfluidics to allow direct microscopic study of live coral polyps. The small and transparent coral micropropagates are ideally suited for live-imaging microscopy, while the microfluidic platform facilitates long-term visualization under controlled environmental conditions. We demonstrate the usefulness of this approach by imaging coral micropropagates at previously unattainable spatio-temporal resolutions, providing new insights into several micro-scale processes including coral calcification, coral–pathogen interaction and the loss of algal symbionts (coral bleaching). Coral-on-a-chip thus provides a powerful method for studying coral physiology in vivo at the micro-scale, opening new vistas in coral biology. PMID:26940983

Printed microfluidic filter for heparinized blood.

Science.gov (United States)

Bilatto, Stanley E R; Adly, Nouran Y; Correa, Daniel S; Wolfrum, Bernhard; Offenhäusser, Andreas; Yakushenko, Alexey

2017-05-01

A simple lab-on-a-chip method for blood plasma separation was developed by combining stereolithographic 3D printing with inkjet printing, creating a completely sealed microfluidic device. In some approaches, one dilutes the blood sample before separation, reducing the concentration of a target analyte and increasing a contamination risk. In this work, a single drop (8  μ l) of heparinized whole blood could be efficiently filtered using a capillary effect without any external driving forces and without dilution. The blood storage in heparin tubes during 24 h at 4 °C initiated the formation of small crystals that formed auto-filtration structures in the sample upon entering the 3D-printed device, with pores smaller than the red blood cells, separating plasma from the cellular content. The total filtration process took less than 10 s. The presented printed plasma filtration microfluidics fabricated with a rapid prototyping approach is a miniaturized, fast and easy-to-operate device that can be integrated into healthcare/portable systems for point-of-care diagnostics.

Microfluidics for single cell analysis

DEFF Research Database (Denmark)

Jensen, Marie Pødenphant

Isolation and manipulation of single cells have gained an increasing interest from researchers because of the heterogeneity of cells from the same cell culture. Single cell analysis can ensure a better understanding of differences between individual cells and potentially solve a variety of clinical...... problems. In this thesis lab on a chip systems for rare single cell analysis are investigated. The focus was to develop a commercial, disposable device for circulating tumour cell (CTC) analysis. Such a device must be able to separate rare cells from blood samples and subsequently capture the specific...... cells, and simultaneously be fabricated and operated at low costs and be user-friendly. These challenges were addressed through development of two microfluidic devices, one for rare cell isolation based on pinched flow fractionation (PFF) and one for single cell capture based on hydrodynamic trapping...

Automated assembly of microfluidic "lab-on-a-disc"

Science.gov (United States)

Berger, M.; Müller, T.; Voebel, T.; Baum, C.; Glennon, T.; Mishra, R.; Kinahan, D.; King, D.; Ducrée, J.; Brecher, C.

2018-02-01

Point-of-care (POC) testing attracts more and more attention in the medical health sector because of their specific property to perform the diagnostic close to the patient. The fast diagnosis right at the hospital or the doctor's office improves the medical reaction time and the chances for a successful healing process. One of this POC test systems is a "Lab-on-a-Disc" (LoaD) which looks like a compact disc crisscrossed with microfluidic tubes and cavities. The fluid to be analysed is placed in the LoaD and an external device then rotates the LoaD. The cavities inside the LoaD and the centrifugal force ensure a clearly defined sequence of the analysis. Furthermore, we aim for an inexpensive manufacture of the medical product without neglecting its quality and functionality. Therefore, the Fraunhofer IPT works on an assembly cell to implement dissoluble films concisely into the disc. This dissoluble film demonstrates its successful usage as a gate for the fluid, which opens after a predefined moment in the cycle. Furthermore, we investigate to integrate a laser welding process into our gantry system and demonstrate its efficiency with the welding of polymer discs. This procedure is clinically safe because no further laser absorption material is needed in the sealing process, which might pollute the LoaD. Moreover, this process allows the alignment of several discs before the welding and therefore leads to precisely manufactured LoaDs in large quantities. All these methods together enable a fast, costefficient and reliable mass production to bring POC testing among the people.

Paper-Plastic Hybrid Microfluidic Device for Smartphone-Based Colorimetric Analysis of Urine.

Science.gov (United States)

Jalal, Uddin M; Jin, Gyeong Jun; Shim, Joon S

2017-12-19

In this work, a disposable paper-plastic hybrid microfluidic lab-on-a-chip (LOC) has been developed and successfully applied for the colorimetric measurement of urine by the smartphone-based optical platform using a "UrineAnalysis" Android app. The developed device was cost-effectively implemented as a stand-alone hybrid LOC by incorporating the paper-based conventional reagent test strip inside the plastic-based LOC microchannel. The LOC device quantitatively investigated the small volume (40 μL) of urine analytes for the colorimetric reaction of glucose, protein, pH, and red blood cell (RBC) in integration with the finger-actuating micropump. On the basis of our experiments, the conventional urine strip showed large deviation as the reaction time goes by, because dipping the strip sensor in a bottle of urine could not control the reaction volume. By integrating the strip sensor in the LOC device for urine analysis, our device significantly improves the time-dependent inconstancy of the conventional dipstick-based urine strip, and the smartphone app used for image analysis enhances the visual assessment of the test strip, which is a major user concern for the colorimetric analysis in point-of-care (POC) applications. As a result, the user-friendly LOC, which is successfully implemented in a disposable format with the smartphone-based optical platform, may be applicable as an effective tool for rapid and qualitative POC urinalysis.

Opto-electronic DNA chip-based integrated card for clinical diagnostics.

Science.gov (United States)

Marchand, Gilles; Broyer, Patrick; Lanet, Véronique; Delattre, Cyril; Foucault, Frédéric; Menou, Lionel; Calvas, Bernard; Roller, Denis; Ginot, Frédéric; Campagnolo, Raymond; Mallard, Frédéric

2008-02-01

Clinical diagnostics is one of the most promising applications for microfluidic lab-on-a-chip or lab-on-card systems. DNA chips, which provide multiparametric data, are privileged tools for genomic analysis. However, automation of molecular biology protocol and use of these DNA chips in fully integrated systems remains a great challenge. Simplicity of chip and/or card/instrument interfaces is amongst the most critical issues to be addressed. Indeed, current detection systems for DNA chip reading are often complex, expensive, bulky and even limited in terms of sensitivity or accuracy. Furthermore, for liquid handling in the lab-on-cards, many devices use complex and bulky systems, either to directly manipulate fluids, or to ensure pneumatic or mechanical control of integrated valves. All these drawbacks prevent or limit the use of DNA-chip-based integrated systems, for point-of-care testing or as a routine diagnostics tool. We present here a DNA-chip-based protocol integration on a plastic card for clinical diagnostics applications including: (1) an opto-electronic DNA-chip, (2) fluid handling using electrically activated embedded pyrotechnic microvalves with closing/opening functions. We demonstrate both fluidic and electric packaging of the optoelectronic DNA chip without major alteration of its electronical and biological functionalities, and fluid control using novel electrically activable pyrotechnic microvalves. Finally, we suggest a complete design of a card dedicated to automation of a complex biological protocol with a fully electrical fluid handling and DNA chip reading.

Fabrication of digital microfluidic devices on flexible paper-based and rigid substrates via screen printing

Science.gov (United States)

Yafia, Mohamed; Shukla, Saurabh; Najjaran, Homayoun

2015-05-01

In this work, a new fabrication method is presented for digital microfluidic (DMF) devices in which the electrodes are generated using the screen printing technique. This method is applicable to both rigid and flexible substrates. The proposed screen printing approach, as a batch printing technique, is advantageous to the widely reported DMF fabrication methods in terms of fabrication time, cost and capability of mass production. Screen printing provides an effective means for printing different types of conductive materials on a variety of substrates. Specifically, screen printing of conductive silver and carbon based inks is performed on paper, glass and wax paper. As a result, the fabricated DMF devices are characterized by being flexible, disposable and incinerable. Hence, the main advantage of screen printing carbon based inks on paper substrates is more pronounced for point-of-care applications that require a large number of low cost DMF chips, and laboratory setups that lack sophisticated microfabrication facilities. The resolution of the printed DMF electrodes generated by this technique is examined for proof of concept using manual screen printing, but higher resolution screens and automated machines are available off-the-shelf, if needed. Another contribution of this research is the improved actuation techniques that facilitate droplet transport in electrode configurations with relatively large electrode spacing to alleviate the disadvantage of lower resolution screens. Thus, we were able to reduce the cost of fabrication significantly without compromising the DMF performance. The paper-based devices have already shown to be effective in continuous microfluidics domain, so the investigation of their applicability in DMF systems is worthwhile. With this in mind, successful integration of a paper-based microchannel with paper-based digital microfluidic chip is demonstrated in this work.

Fabrication of digital microfluidic devices on flexible paper-based and rigid substrates via screen printing

International Nuclear Information System (INIS)

Yafia, Mohamed; Shukla, Saurabh; Najjaran, Homayoun

2015-01-01

In this work, a new fabrication method is presented for digital microfluidic (DMF) devices in which the electrodes are generated using the screen printing technique. This method is applicable to both rigid and flexible substrates. The proposed screen printing approach, as a batch printing technique, is advantageous to the widely reported DMF fabrication methods in terms of fabrication time, cost and capability of mass production. Screen printing provides an effective means for printing different types of conductive materials on a variety of substrates. Specifically, screen printing of conductive silver and carbon based inks is performed on paper, glass and wax paper. As a result, the fabricated DMF devices are characterized by being flexible, disposable and incinerable. Hence, the main advantage of screen printing carbon based inks on paper substrates is more pronounced for point-of-care applications that require a large number of low cost DMF chips, and laboratory setups that lack sophisticated microfabrication facilities. The resolution of the printed DMF electrodes generated by this technique is examined for proof of concept using manual screen printing, but higher resolution screens and automated machines are available off-the-shelf, if needed. Another contribution of this research is the improved actuation techniques that facilitate droplet transport in electrode configurations with relatively large electrode spacing to alleviate the disadvantage of lower resolution screens. Thus, we were able to reduce the cost of fabrication significantly without compromising the DMF performance. The paper-based devices have already shown to be effective in continuous microfluidics domain, so the investigation of their applicability in DMF systems is worthwhile. With this in mind, successful integration of a paper-based microchannel with paper-based digital microfluidic chip is demonstrated in this work. (note)

Nucleic acid and protein extraction from electropermeabilized E. coli cells on a microfluidic chip

DEFF Research Database (Denmark)

Matos, T.; Senkbeil, Silja; Mendonça, A.

2013-01-01

technique has been developed which is based on exposing E. coli cells to low voltages to allow extraction of nucleic acids and proteins. The flow-through electropermeability chip used consists of a microfluidic channel with integrated gold electrodes that promote cell envelope channel formation at low...

PMMA to SU-8 Bonding for Polymer Based Lab-on-a-chip Systems with Integrated Optics

DEFF Research Database (Denmark)

Olsen, Brian Bilenberg; Nielsen, Theodor; Nilsson, Daniel

2003-01-01

An adhesive bonding technique for wafer-level sealing of SU-8 based lab-on-a-chip microsystems with integrated optical components is presented. Microfluidic channels and optical components, e.g. waveguides, are fabricated in cross-linked SU-8 and sealed with a Pyrex glass substrate by means...... strength of 16 MPa is achieved at bonding temperatures between 110 oC and 120oC, at a bonding force of 2000 N on a 4-inch wafer. The optical propagation loss of multi-mode 10ym (thickness)x 30ym (width)SU-8 waveguides is measured. The propagation loss in PMMA bonded waveguide struc-tures is more than 5 d......B/cm lower, at wavelengths between 600nm and 900 nm, than in similar structures bonded by an intermediate layer of SU-8. Furthermore 950K PMMA shows no tendency to flow into the bonded structures during bonding because of its high viscosity....

MISENS DEVICE AS A NEW AUTOMATED BIOSENSING PLATFORM BASED ON REAL-TIME ELECTROCHEMICAL PROFILING (REP

Directory of Open Access Journals (Sweden)

yıldız uludağ

2016-09-01

Full Text Available In various fields like health, environmental control, food security and military defense; there is an increasing demand for on-site detection, fast identification and urgent response which brings the necessity to employ laboratory detection procedures on standalone automatic devices. In response to that TUBITAK BILGEM’s Bioelectronic Devices and Systems Group has been developing portable and fully automated biosensor devices using optical and electrochemical biosensor detection techniques. Here we describe a new integrated and fully automated lab-on-a-chip based biosensor device ‘MiSens’. The key features of the MiSens include a new electrode array, an integrated microfluidic system and real-time amperometric measurements during the flow of enzyme substrate. While simple protocols can be controlled from the LCD display on the device, other main device control procedures can be run wireless by a tablet/PC using the MiCont™ software developed by the team. For the device, a new plug and play type sensor chip docking station has been designed that with one move it enables the formation of a ~ 7-10 µl capacity flow cell on the electrode array with the necessary microfluidic and electronic connections. The MiSens device has been developed by our multi-disciplinary team by integrating and automatising the earlier developed sensing platform REP™ (Real-time Electrochemical Profiling. The performance of the MiSens device has been tested using cyclic voltammetry and amperometry tests and the results were compared with an of the shelf potantiostat.

Optical bio-sensors in microfluidic chips

NARCIS (Netherlands)

Pollnau, Markus; Dongre, C.; Pham Van So, P.V.S.; Bernhardi, Edward; Worhoff, Kerstin; de Ridder, R.M.; Hoekstra, Hugo

2012-01-01

Direct femtosecond laser writing is used to integrate optical waveguides that intersect the microfluidic channels in a commercial optofluidic chip. With laser excitation, fluorescently labeled DNA molecules of different sizes are separated by capillary electrophoresis with high operating speed and

Cobalt hexacyanoferrate modified multi-walled carbon nanotubes/graphite composite electrode as electrochemical sensor on microfluidic chip

Energy Technology Data Exchange (ETDEWEB)

Li Xinchun [School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road of Higher Education Mega Centre, Guangzhou 510006 (China); Chen Zuanguang, E-mail: chenzg@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road of Higher Education Mega Centre, Guangzhou 510006 (China); Zhong Yuwen, E-mail: yu0106@163.com [Center for Disease Control and Prevention of Guangdong Province, 176 Xingangxi, Guangzhou 510300 (China); Yang Fan; Pan Jianbin; Liang Yajing [School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road of Higher Education Mega Centre, Guangzhou 510006 (China)

2012-01-13

high sensitivity, hold great potential for hydrazine compounds assay in the lab-on-a-chip system.

A one-step strategy for ultra-fast and low-cost mass production of plastic membrane microfluidic chips.

Science.gov (United States)

Hu, Chong; Lin, Sheng; Li, Wanbo; Sun, Han; Chen, Yangfan; Chan, Chiu-Wing; Leung, Chung-Hang; Ma, Dik-Lung; Wu, Hongkai; Ren, Kangning

2016-10-05

An ultra-fast, extremely cost-effective, and environmentally friendly method was developed for fabricating flexible microfluidic chips with plastic membranes. With this method, we could fabricate plastic microfluidic chips rapidly (within 12 seconds per piece) at an extremely low cost (less than $0.02 per piece). We used a heated perfluoropolymer perfluoroalkoxy (often called Teflon PFA) solid stamp to press a pile of two pieces of plastic membranes, low density polyethylene (LDPE) and polyethylene terephthalate (PET) coated with an ethylene-vinyl acetate copolymer (EVA). During the short period of contact with the heated PFA stamp, the pressed area of the membranes permanently bonded, while the LDPE membrane spontaneously rose up at the area not pressed, forming microchannels automatically. These two regions were clearly distinguishable even at the micrometer scale so we were able to fabricate microchannels with widths down to 50 microns. This method combines the two steps in the conventional strategy for microchannel fabrication, generating microchannels and sealing channels, into a single step. The production is a green process without using any solvent or generating any waste. Also, the chips showed good resistance against the absorption of Rhodamine 6G, oligonucleotides, and green fluorescent protein (GFP). We demonstrated some typical microfluidic manipulations with the flexible plastic membrane chips, including droplet formation, on-chip capillary electrophoresis, and peristaltic pumping for quantitative injection of samples and reagents. In addition, we demonstrated convenient on-chip detection of lead ions in water samples by a peristaltic-pumping design, as an example of the application of the plastic membrane chips in a resource-limited environment. Due to the high speed and low cost of the fabrication process, this single-step method will facilitate the mass production of microfluidic chips and commercialization of microfluidic technologies.

Semi-automated lab-on-a-chip for dispensing GA-68 radiotracers

Energy Technology Data Exchange (ETDEWEB)

Weinberg, Irving [Weinberg Medical Physics LLC, Bethesda, MD (United States)

2014-03-12

We solved a technical problem that is hindering American progress in molecular medicine, and restricting US citizens from receiving optimal diagnostic care. Specifically, the project deals with a mother/daughter generator of positron-emitting radiotracers (Ge-68/Ga-68). These generator systems are approved in Europe but cannot be used in the USA, because of safety issues related to possible breakthrough of long-lived Ge-68 (mother) atoms. Europeans have demonstrated abilities of Ga-68-labeled radiotracers to image cancer foci with high sensitivity and specificity, and to use such methods to effectively plan therapy.The USA Food and Drug Administration (FDA) and Nuclear Regulatory Commission (NRC) have taken the position that every patient administration of Ga-68 should be preceded by an assay demonstrated that Ge-68 breakthrough is within acceptable limits. Breakthrough of parent elements is a sensitive subject at the FDA, as evidenced by the recent recall of Rb-82 generators due to inadvertent administrations of Sr-82. Commercially, there is no acceptable rapid method for assaying breakthrough of Ge-68 prior to each human administration. The gamma emissions of daughter Ga-68 have higher energies than the parent Ge-68, so that the shielding assays typically employed for Mo-99/Tc-99m generators cannot be applied to Ga-68 generators. The half-life of Ga-68 is 68 minutes, so that the standard 10-half-life delay (used to assess breakthrough in Sr-82/Rb-82 generators) cannot be applied to Ga-68 generators. As a result of the aforementioned regulatory requirements, Ga-68 generators are sold in the USA for animal use only.The American clinical community’s inability to utilize Ga-68 generators impairs abilities to treat patients domestically, and puts the USA at a disadvantage in developing exportable products. The proposed DOE project aimed to take advantage of recent technological advances developed for lab-on-a-chip (LOC) applications. Based on our experiences

Rapid wasted-free microfluidic fabrication based on ink-jet approach for microfluidic sensing applications

Science.gov (United States)

Jarujareet, Ungkarn; Amarit, Rattasart; Sumriddetchkajorn, Sarun

2016-11-01

Realizing that current microfluidic chip fabrication techniques are time consuming and labor intensive as well as always have material leftover after chip fabrication, this research work proposes an innovative approach for rapid microfluidic chip production. The key idea relies on a combination of a widely-used inkjet printing method and a heat-based polymer curing technique with an electronic-mechanical control, thus eliminating the need of masking and molds compared to typical microfluidic fabrication processes. In addition, as the appropriate amount of polymer is utilized during printing, there is much less amount of material wasted. Our inkjet-based microfluidic printer can print out the desired microfluidic chip pattern directly onto a heated glass surface, where the printed polymer is suddenly cured. Our proof-of-concept demonstration for widely-used single-flow channel, Y-junction, and T-junction microfluidic chips shows that the whole microfluidic chip fabrication process requires only 3 steps with a fabrication time of 6 minutes.

SU-8 as a material for lab-on-a-chip-based mass spectrometry.

Science.gov (United States)

Arscott, Steve

2014-10-07

This short review focuses on the application of SU-8 for the microchip-based approach to the miniaturization of mass spectrometry. Chip-based mass spectrometry will make the technology commonplace and bring benefits such as lower costs and autonomy. The chip-based miniaturization of mass spectrometry necessitates the use of new materials which are compatible with top-down fabrication involving both planar and non-planar processes. In this context, SU-8 is a very versatile epoxy-based, negative tone resist which is sensitive to ultraviolet radiation, X-rays and electron beam exposure. It has a very wide thickness range, from nanometres to millimetres, enabling the formation of mechanically rigid, very high aspect ratio, vertical, narrow width structures required to form microfluidic slots and channels for laboratory-on-a-chip design. It is also relatively chemically resistant and biologically compatible in terms of the liquid solutions used for mass spectrometry. This review looks at the impact and potential of SU-8 on the different parts of chip-based mass spectrometry - pre-treatment, ionization processes, and ion sorting and detection.

Heterogenous integration of a thin-film GaAs photodetector and a microfluidic device on a silicon substrate

International Nuclear Information System (INIS)

Song, Fuchuan; Xiao, Jing; Udawala, Fidaali; Seo, Sang-Woo

2011-01-01

In this paper, heterogeneous integration of a III–V semiconductor thin-film photodetector (PD) with a microfluidic device is demonstrated on a SiO 2 –Si substrate. Thin-film format of optical devices provides an intimate integration of optical functions with microfluidic devices. As a demonstration of a multi-material and functional system, the biphasic flow structure in the polymeric microfluidic channels was co-integrated with a III–V semiconductor thin-film PD. The fluorescent drops formed in the microfluidic device are successfully detected with an integrated thin-film PD on a silicon substrate. The proposed three-dimensional integration structure is an alternative approach to combine optical functions with microfluidic functions on silicon-based electronic functions.

Recent advances in nanoplasmonic biosensors: applications and lab-on-a-chip integration

Directory of Open Access Journals (Sweden)

Lopez Gerardo A.

2016-08-01

Full Text Available Motivated by the recent progress in the nanofabrication field and the increasing demand for cost-effective, portable, and easy-to-use point-of-care platforms, localized surface plasmon resonance (LSPR biosensors have been subjected to a great scientific interest in the last few years. The progress observed in the research of this nanoplasmonic technology is remarkable not only from a nanostructure fabrication point of view but also in the complete development and integration of operative devices and their application. The potential benefits that LSPR biosensors can offer, such as sensor miniaturization, multiplexing opportunities, and enhanced performances, have quickly positioned them as an interesting candidate in the design of lab-on-a-chip (LOC optical biosensor platforms. This review covers specifically the most significant achievements that occurred in recent years towards the integration of this technology in compact devices, with views of obtaining LOC devices. We also discuss the most relevant examples of the use of the nanoplasmonic biosensors for real bioanalytical and clinical applications from assay development and validation to the identification of the implications, requirements, and challenges to be surpassed to achieve fully operative devices.

Acoustically and Electrokinetically Driven Transport in Microfluidic Devices

Science.gov (United States)

Sayar, Ersin

Electrokinetically driven flows are widely employed as a primary method for liquid pumping in micro-electromechanical systems. Mixing of analytes and reagents is limited in microfluidic devices due to the low Reynolds number of the flows. Acoustic excitations have recently been suggested to promote mixing in the microscale flow systems. Electrokinetic flows through straight microchannels were investigated using the Poisson-Boltzmann and Nernst-Planck models. The acoustic wave/fluid flow interactions in a microchannel were investigated via the development of two and three-dimensional dynamic predictive models for flows with field couplings of the electrical, mechanical and fluid flow quantities. The effectiveness and applicability of electrokinetic augmentation in flexural plate wave micropumps for enhanced capabilities were explored. The proposed concept can be exploited to integrate micropumps into complex microfluidic chips improving the portability of micro-total-analysis systems along with the capabilities of actively controlling acoustics and electrokinetics for micro-mixer applications. Acoustically excited flows in microchannels consisting of flexural plate wave devices and thin film resonators were considered. Compressible flow fields were considered to accommodate the acoustic excitations produced by a vibrating wall. The velocity and pressure profiles for different parameters including frequency, channel height, wave amplitude and length were investigated. Coupled electrokinetics and acoustics cases were investigated while the electric field intensity of the electrokinetic body forces and actuation frequency of acoustic excitations were varied. Multifield analysis of a piezoelectrically actuated valveless micropump was also presented. The effect of voltage and frequency on membrane deflection and flow rate were investigated. Detailed fluid/solid deformation coupled simulations of piezoelectric valveless micropump have been conducted to predict the

Mkit: A Cell Migration Assay Based on Microfluidic Device and Smartphone

Science.gov (United States)

Yang, Ke; Wu, Jiandong; Peretz-Soroka, Hagit; Zhu, Ling; Li, Zhigang; Sang, Yaoshuo; Hipolito, Jolly; Zhang, Michael; Santos, Susy; Hillier, Craig; de Faria, Ricardo Lobato; Liu, Yong; Lin, Francis

2017-01-01

Mobile sensing based on the integration of microfluidic device and smartphone, so-called MS2 technology, has enabled many applications over recent years, and continues to stimulate growing interest in both research communities and industries. In particular, it has been envisioned that MS2 technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction, in this paper, we describe the development of a MS2-based cell functional assay for testing cell migration (the Mkit). The system is constructed as an integrated test kit, which includes microfluidic chips, a smartphone-based imaging platform, the phone apps for image capturing and data analysis, and a set of reagent and accessories for performing the cell migration assay. We demonstrated that the Mkit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore, neutrophil chemotaxis can be tested from a drop of whole blood using the Mkit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the Mkit. In addition to research applications, we demonstrated the effective use of the Mkit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus, this developed Mkit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications. PMID:28772229

Portable Analyzer Based on Microfluidic/Nanoengineered electrochemical Sensors for in Situ Characterization of Mixed Wastes

International Nuclear Information System (INIS)

Wang, Joseph

2007-01-01

This project aimed on the development of compact microchip sensing devices for on-site monitoring of pollutants in contaminated DOE sites. As described in this report, we have made a substantial progress, and introduced effective routes for improving the on-site detection of toxic metals and for interfacing microfluidic (Lab-on-Chip) sensing devices with the real world. This activity has been very productive and has already been described in 12 research papers (published in major international journals). The resulting microchip sensor technology should allow testing for toxic metals and other major pollutants to be performed more rapidly, inexpensively, and reliably in a field setting. These new analytical capabilities resulted from the generous DOE support will facilitate the characterization and remediation of mixed waste contaminated sites.

Integrated Microfluidic Sensor System with Magnetostrictive Resonators

KAUST Repository

Liang, Cai; Kosel, Jü rgen; Gooneratne, Chinthaka

2011-01-01

The present embodiments describe a method that integrates a magnetostrictive sensor with driving and detecting elements into a microfluidic chip to detect a chemical, biochemical or biomedical species. These embodiments may also measure the properties of a fluid such as viscosity, pH values. The whole system can be referred to lab-on-a-chip (LOC) or micro-total-analysis-systems (.mu.TAS). In particular, this present embodiments include three units, including a microfluidics unit, a magnetostrictive sensor, and driving/detecting elements. An analyzer may also be provided to analyze an electrical signal associated with a feature of a target specimen.

Integrated Microfluidic Sensor System with Magnetostrictive Resonators

KAUST Repository

Liang, Cai

2011-12-08

The present embodiments describe a method that integrates a magnetostrictive sensor with driving and detecting elements into a microfluidic chip to detect a chemical, biochemical or biomedical species. These embodiments may also measure the properties of a fluid such as viscosity, pH values. The whole system can be referred to lab-on-a-chip (LOC) or micro-total-analysis-systems (.mu.TAS). In particular, this present embodiments include three units, including a microfluidics unit, a magnetostrictive sensor, and driving/detecting elements. An analyzer may also be provided to analyze an electrical signal associated with a feature of a target specimen.

Optical sensing system based on wireless paired emitter detector diode device and ionogels for lab-on-a-disc water quality analysis.

Science.gov (United States)

Czugala, Monika; Gorkin, Robert; Phelan, Thomas; Gaughran, Jennifer; Curto, Vincenzo Fabio; Ducrée, Jens; Diamond, Dermot; Benito-Lopez, Fernando

2012-12-07

This work describes the first use of a wireless paired emitter detector diode device (PEDD) as an optical sensor for water quality monitoring in a lab-on-a-disc device. The microfluidic platform, based on an ionogel sensing area combined with a low-cost optical sensor, is applied for quantitative pH and qualitative turbidity monitoring of water samples at point-of-need. The autonomous capabilities of the PEDD system, combined with the portability and wireless communication of the full device, provide the flexibility needed for on-site water testing. Water samples from local fresh and brackish sources were successfully analysed using the device, showing very good correlation with standard bench-top systems.

Screening reactive oxygen species scavenging properties of platinum nanoparticles on a microfluidic chip.

Science.gov (United States)

Zheng, Wenfu; Jiang, Bo; Hao, Yi; Zhao, Yuyun; Zhang, Wei; Jiang, Xingyu

2014-09-12

Hyperglycemia, hyperlipidemia and inflammation are key risk factors for atherosclerosis and can lead to overproduction of reactive oxygen species (ROS), which plays a critical role in vascular endothelial dysfunction and subsequent progress of atherosclerosis. However, there is currently a lack of effective drugs that deal with ROS. Platinum nanoparticles (Pt-NPs) have proven to be promising antioxidant drugs in vitro and in vivo. To optimize the efficacy of Pt-NP based drugs, we synthesized and characterized the ROS scavenging properties of three kinds of small molecules that capped Pt-NPs (Pt-AMP-NPs, Pt-ATT-NPs, Pt-MI-NPs) on a blood vessel-mimicking microfluidic chip. The Pt-NPs showed superior superoxide dismutase (SOD)-like functions and can scavenge ROS and recover compromised cell-cell junctions under hyperglycemic, hyperlipidemic and proinflammatory conditions. Amongst these NPs, Pt-AMP-NPs showed the most superior antioxidant properties, suggesting its potency to serve as a novel drug to treat vascular diseases such as atherosclerosis. Our microfluidic chip, providing physiological hemodynamic conditions for the experiments, is potentially a promising tool for a wide range of biological research on the vascular system.

Fabrication of All Glass Bifurcation Microfluidic Chip for Blood Plasma Separation

Directory of Open Access Journals (Sweden)

Hyungjun Jang

2017-02-01

Full Text Available An all-glass bifurcation microfluidic chip for blood plasma separation was fabricated by a cost-effective glass molding process using an amorphous carbon (AC mold, which in turn was fabricated by the carbonization of a replicated furan precursor. To compensate for the shrinkage during AC mold fabrication, an enlarged photoresist pattern master was designed, and an AC mold with a dimensional error of 2.9% was achieved; the dimensional error of the master pattern was 1.6%. In the glass molding process, a glass microchannel plate with negligible shape errors (~1.5% compared to AC mold was replicated. Finally, an all-glass bifurcation microfluidic chip was realized by micro drilling and thermal fusion bonding processes. A separation efficiency of 74% was obtained using the fabricated all-glass bifurcation microfluidic chip.

Integrated lenses in polystyrene microfluidic devices

KAUST Repository

Fan, Yiqiang

2013-04-01

This paper reports a new method for integrating microlenses into microfluidic devices for improved observation. Two demonstration microfluidic devices were provided which were fabricated using this new technique. The integrated microlenses were fabricated using a free-surface thermo-compression molding method on a polystyrene (PS) sheet which was then bonded on top of microfluidic channels as a cover plate, with the convex microlenses providing a magnified image of the channel for the easier observation of the flow in the microchannels. This approach for fabricating the integrated microlens in microfluidic devices is rapid, low cost and without the requirement of cleanroom facilities. © 2013 IEEE.

Microfluidic organ-on-chip technology for blood-brain barrier research.

Science.gov (United States)

van der Helm, Marinke W; van der Meer, Andries D; Eijkel, Jan C T; van den Berg, Albert; Segerink, Loes I

2016-01-01

Organs-on-chips are a new class of microengineered laboratory models that combine several of the advantages of current in vivo and in vitro models. In this review, we summarize the advances that have been made in the development of organ-on-chip models of the blood-brain barrier (BBBs-on-chips) and the challenges that are still ahead. The BBB is formed by specialized endothelial cells and separates blood from brain tissue. It protects the brain from harmful compounds from the blood and provides homeostasis for optimal neuronal function [corrected]. Studying BBB function and dysfunction is important for drug development and biomedical research. Microfluidic BBBs-on-chips enable real-time study of (human) cells in an engineered physiological microenvironment, for example incorporating small geometries and fluid flow as well as sensors. Examples of BBBs-on-chips in literature already show the potential of more realistic microenvironments and the study of organ-level functions. A key challenge in the field of BBB-on-chip development is the current lack of standardized quantification of parameters such as barrier permeability and shear stress. This limits the potential for direct comparison of the performance of different BBB-on-chip models to each other and existing models. We give recommendations for further standardization in model characterization and conclude that the rapidly emerging field of BBB-on-chip models holds great promise for further studies in BBB biology and drug development.

Mixing in a Microfluid Device

DEFF Research Database (Denmark)

Hjorth, Poul G.; Deryabin, Mikhail

Mixing of fluids in microchannels cannot rely on turbulence since the flow takes place at extremly low Reynolds numbers. Various active and passive devices have been developed to induce mixing in microfluid flow devices. We describe here a model of an active mixer where a transverse periodic flow...

Controlled and tunable polymer particles' production using a single microfluidic device

Science.gov (United States)

Amoyav, Benzion; Benny, Ofra

2018-04-01

Microfluidics technology offers a new platform to control liquids under flow in small volumes. The advantage of using small-scale reactions for droplet generation along with the capacity to control the preparation parameters, making microfluidic chips an attractive technology for optimizing encapsulation formulations. However, one of the drawback in this methodology is the ability to obtain a wide range of droplet sizes, from sub-micron to microns using a single chip design. In fact, typically, droplet chips are used for micron-dimension particles, while nanoparticles' synthesis requires complex chips design (i.e., microreactors and staggered herringbone micromixer). Here, we introduce the development of a highly tunable and controlled encapsulation technique, using two polymer compositions, for generating particles ranging from microns to nano-size using the same simple single microfluidic chip design. Poly(lactic-co-glycolic acid) (PLGA 50:50) or PLGA/polyethylene glycol polymeric particles were prepared with focused-flow chip, yielding monodisperse particle batches. We show that by varying flow rate, solvent, surfactant and polymer composition, we were able to optimize particles' size and decrease polydispersity index, using simple chip designs with no further related adjustments or costs. Utilizing this platform, which offers tight tuning of particle properties, could offer an important tool for formulation development and can potentially pave the way towards a better precision nanomedicine.