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At least 127 records · Page 7Linked to original sources

Microfluidic tools for studying the specific binding, adsorption, and displacement of proteins at interfaces.

A combination of temperature and concentration gradient microfluidic devices were employed to study the mechanistic details of biomacromolecule interactions at oxide interfaces. These lab-on-a-chip techniques allowed high-throughput, multiplexed data collection using only nanoliters of analyte. The three examples presented demonstrate rapid data acquisition relative to standard methods. First, we show ligand-receptor binding data for multivalent binding between membrane-bound ligands and incoming aqueous proteins with several binding pockets. A model is described for obtaining both the first and second dissociation constant for the reaction. The second example employs temperature gradient microfluidics to study the thermoresponsive properties of polymers and proteins. Both the folding mechanism and subsequent formation of an aqueous two-phase system were followed. Finally, these microfluidic techniques were combined with fluorescence microscopy and nonlinear optical spectroscopy to elucidate the mechanism of fibrinogen displacement from silica surfaces. This combination of methods enabled both direct and indirect observation of protein conformational changes.

Adsorption↗

Lab-on-a-chip for drug development.

Significant advances have been made in the development of micro-scale technologies for biomedical and drug discovery applications. The first generation of microfluidics-based analytical devices have been designed and are already functional. Microfluidic devices offer unique advantages in sample handling, reagent mixing, separation, and detection. We introduce and review microfluidic concepts, microconstruction techniques, and methods such as flow-injection analysis, electrokinesis, and cell manipulation. Advances in micro-device technology for proteomics, sample preconditioning, immunoassays, electrospray ionization mass spectrometry, and polymerase chain reaction are also reviewed.

Animals↗

DNA detection by integrable electronics.

This paper presents a new electronic methodology to detect DNA hybridization for rapid identification of diseases, as well as food and environmental monitoring on a genetic base. The proposed solution exploits a new (electrical) capacitive measurement circuit, not requiring any prior labeling of the DNA (as it is often the case with the commonly employed optical detection). The sensitivity, the reliability, and the reproducibility of this device have been evaluated by experiments performed with a (non-integrated) prototype implementation, easily integrable in IC and/or micro-fabricated lab-on-a-chip.

Adsorption↗

Design and fabrication of a silica on silicon integrated optical biochip as a fluorescence microarray platform.

Previous research into the use of Flame Hydrolysis Deposition (FHD) of glasses in integrated optics has focused on the successful commercial exploitation of low cost optical devices within the field of telecommunications and optoelectronics. Recently we have sought to apply these fabrication technologies to the development of optical biochips, utilising their ability to be integrated with microfluidics as a 'Lab-on-a-chip' platform. In this paper, we carry this development forward by seeking to create a microarray of integrated optical sensing elements, addressed using a glass-polymer hybrid technology in which poly(dimethylsiloxane), PDMS, is used as an elastomeric packaging over-layer. In particular, we describe the wide range of modelling and microfabrication processes required for the successful manufacture, integration and packaging of such arrays. The integration of both optical and fluidic circuits in this device avoids precise alignment requirements and results in a compact, robust and reliable device. Finally, in this paper, we describe the implementation of a pumping system for delivering small amounts of fluid across the array together with an optical signal treatment.

Carbocyanines↗

Electrically actuated, pressure-driven microfluidic pumps.

In order to make the lab-on-a-chip concept a reality, it is desirable to have an integrated component capable of pumping fluids through microchannels. We have developed novel, electrically actuated micropumps and have integrated them with microfluidic systems. These devices utilize the build-up of electrolysis gases to achieve pressure-driven pumping, only require small voltages (approximately 10 V), and have approximate dimensions of 5 cm x 3 cm x 2 cm. Furthermore, these micropumps are composed of relatively inexpensive materials, and the reversible sealability of their poly(dimethylsiloxane) body to different microfluidic arrays enables repeated uses of the same pump. Under an applied potential of 10 V, three different micropumps had average flow rates of 8-13 microL min(-1) for water being pumped through five different 2 cm-long, 5500 microm(2) cross-sectional-area channels in poly(methyl methacrylate), in approximate agreement with predicted pump rates. We have also evaluated pump operation at the lower applied potential of 8 V and observed an average flow rate of 6.1 microL min(-1) for a pump-channel system. The current micropump design is capable of sustaining pumping pressures in the range of 300 kPa. The various advantages of these micropumps make them well suited for use in lab-on-a-chip analysis techniques.

Microcomputers↗

Low-voltage electroosmosis pump for stand-alone microfluidics devices.

Two types of low-voltage electroosmosis pumps were developed using microfabrication technology for usage in handy or stand-alone applications of the micrototal analysis systems (micro-TAS) and the lab-on-a-chip. This was done by making a thin (< 1 microm) region in the flow path and by only applying voltages near this thin region using electrodes inserted into the flow path. The inserted electrodes must be free from bubble formation and be gas-tight in order to avoid pressure leakage. For these electrodes, Ag/AgCl or a gel salt bridge was used. For patterning the gel on the chip, a hydrophilic photopolymerization gel and a photolithographic technique were optimized for producing a gel with higher electric conductivity and higher mechanical strength. For high flow rate application, wide (33.2 mm) and thin (400 nm) pumping channels were compacted into a 1 mm x 6 mm area by folding. This pump achieves an 800 Pa static pressure and a flow of 415 nL/min at 10 V. For high-pressure application, a pump was designed with the thin and thick regions in series and positive and negative electrodes were inserted between them alternatively. This pump could increase the pumping pressure without increasing the supply voltage. A pump with 10-stage connections generated a pressure of 25 kPa at 10 V.

Acrylic Resins↗

A micromachined capillary electrophoresis chip with fully integrated electrodes for separation and electrochemical detection.

A novel analytical microsystem with fully integrated electrodes for electrophoresis and amperometrical detection is described. With respect to the lab-on-a-chip concept a capillary electrophoresis (CE) microsystem has been fabricated with a total of six gold electrodes for sample injection, separation and electrochemical detection using standard microfabrication technologies. The device is a ready-to-use system that does not need any extra mechanical apparatus for electrode insertion. The CE-chip has successfully been tested by measuring hydrogen peroxide, ascorbic acid and uric acid simultaneously. All three oxidizable species could be detected in less than 70 s. Glucose was detected by performing an enzymatic reaction along the separation channel. The microsystem showed a very good reproducibility.

Ascorbic Acid↗

Levitation and movement of human tumor cells using a printed circuit board device based on software-controlled dielectrophoresis.

In this study we describe an original, efficient, and innovative printed circuit board (PCB) device able to generate dielectrophoresis-based, software-controlled cages that can be moved to any place inside a microchamber. Depending on their dielectrophoretic properties, eukaryotic cells can be "entrapped" in cages and moved under software control. The main conclusion gathered from the experimental data reported is that the PCB device based on dielectrophoresis permits levitation and movement of different tumor cells at different dielectrophoresis conditions. The results presented herein are therefore the basis for experiments aimed at forced interactions or separation of eukaryotic cells using "lab-on-a-chip." In fact, because many cages can be controlled at the same time, and two or more cages can be forced to share the same or a different location, it is possible, in principle, either to bring in contact cells of a differing histotype or to separate them.

Animals↗

Electrophoresis in microfabricated devices using photopolymerized polyacrylamide gels and electrode-defined sample injection.

Microfabrication techniques have become increasingly popular in the development of the next generation of DNA analysis systems. While significant progress has been reported by many researchers, complete microfabricated integrated DNA analysis devices are still in the earliest stages of development. Most miniaturized analysis systems have incorporated noncross-linked polymer solutions as the separation medium of choice and the operation of these systems necessitates the use of high electric fields and long separation lengths. In this paper, we present two techniques that may help alleviate this problem and accelerate the development of the so-called 'lab-on-a-chip' systems. We present the use of photodefinable polyacrylamide gels as a sieving medium for DNA electrophoresis. These gels offer the significant advantages of faster curing times, locally controlled gel interface, and simpler handling over chemically polymerized gels. We also introduce an electrode-defined sample compaction and injection technique. This technique helps achieve sample compaction without migration into the gel and offers significant control over the size and application of the sample plug. The use of these technologies for double-stranded DNA separations in microfabricated separation systems is demonstrated.

Acrylic Resins↗

Continuous cell partitioning using an aqueous two-phase flow system in microfluidic devices.

We present a novel microfluidic system in which an aqueous two-phase laminar flow is stably formed, and the continuous partitioning of relatively large cells can be performed, eliminating the influence of gravity. In this study, plant cell aggregates whose diameters were 37-96 microm were used as model particles. We first performed cell partitioning using a simple straight microchannel having two inlets and two outlets and examined the effects of the flow rate and the phase width on partitioning efficiency. Second, by using a microchannel with a pinched segment, the partitioning efficiency was successfully improved. This microscale aqueous two-phase flow system can further be incorporated into micro total analysis systems (microTAS) or lab-on-a-chip technology, owing to its simplicity, applicability, and biocompatibility.

Cell Aggregation↗

Efficient energy based modeling and experimental validation of liquid filling in planar micro-fluidic components and networks.

This paper presents a model that describes how liquid flow fills micro-fluidic components and networks. As an alternative to computational fluid dynamic (CFD) simulations, we use a constrained energy minimization approach. This approach is based on two assumptions that hold in many micro-fluidic devices: (i) The length scales are small, and we consider slow filling rates, hence fluid momentum and viscous terms are small compared to surface tension forces, consequently the liquid/gas interfaces can be viewed as a succession of quasi-steady equilibrium configurations. (ii) Any equilibrium configuration corresponds to a surface tension energy minima which is constrained by the device shape and the volume of liquid in the device. The model is developed for planar micro-fluidic devices, is based on a fundamental physical principle, and shows accurate agreement with experimental data. It takes us only a few minutes to evaluate the model for a planar component of any shape using the Surface Evolver software, and this is significantly less then the computer run time required for CFD simulations. Moreover, once a library of component models has been created (which takes less than an hour of computer time) it then takes only seconds to simulate different network architectures with thousands of components. This fast "reconfigure the network and simulate in seconds" capability is essential for the design of truly complex networks that will enable the next generation of passive, micro-fluidic, lab-on-a-chip systems.

Computer Simulation↗

Microfabricated capillary electrophoresis amino acid chirality analyzer for extraterrestrial exploration.

Chiral separations of fluorescein isothiocyanate-labeled amino acids have been performed on a microfabricated capillary electrophoresis chip to explore the feasibility of using such devices to analyze for extinct or extant life signs in extraterrestrial environments. The test system consists of a folded electrophoresis channel (19.0 cm long x 150 microns wide x 20 microns deep) that was photolithographically fabricated in a 10-cm-diameter glass wafer sandwich, coupled to a laser-excited confocal fluorescence detection apparatus providing subattomole sensitivity. Using a sodium dodecyl sulfate/gamma-cyclodextrin pH 10.0 carbonate electrophoresis buffer and a separation voltage of 550 V/cm at 10 degrees C, baseline resolution was observed for Val, Ala, Glu, and Asp enantiomers and Gly in only 4 min. Enantiomeric ratios were determined for amino acids extracted from the Murchison meteorite, and these values closely matched values determined by HPLC. These results demonstrate the feasibility of using microfabricated lab-on-a-chip systems to analyze extraterrestrial samples for amino acids.

Amino Acids↗

Lab-on-a-chip: applications in proteomics.

Recent advances in chip-based separation of proteins provide methods that are faster and more convenient than conventional gel electrophoresis. Rapid and automated protein sizing on a chip is at the commercial stage and first attempts have been made to perform two-dimensional separation on a chip. Numerous designs have been described to interface a microfluidic chip to a mass spectrometer. Impressive integration efforts are demonstrated by the ability to perform on-chip trypsin digestion, separation and injection into a mass spectrometer with a single device.

Animals↗

Selective ion extraction: a separation method for microfluidic devices.

A separation concept, selective ion extraction (SIE), is proposed on the basis of the combination of hydrodynamic and electrokinetic flow controls in microfluidic devices. Using a control system with multiple pressure and voltage sources, the hydrodynamic flow and electric field in any section of the microfluidic network can be set to desired values. Mixtures of compounds sent into a T-junction on a chip can be completely separated into different channels on the basis of their electrophoretic mobilities. A simple velocity balance model proved useful for predicting the voltage and pressure settings needed for separation. SIE provides a highly efficient separation with minimal additional dispersion. It is an ideal technique for high-throughput screening systems and demonstrates the power of lab-on-a-chip systems.

Journal Article↗

Interconnected reversible lab-on-a-chip technology.

Interconnected lab-on-a-chip modules with minimal dead volume have been developed resulting in the 'plug and play' concept based upon a reversible bonding process. This paper describes the detail of a chip to chip interconnection method, where devices have been aligned and bonded within 15 min and rapidly disassembled in under 5 min. The transport of fluorescein between the chip modules was used as a model microfluidic system and analysed in order to demonstrate the electrophoretic performance of the device and the interconnected junction. Using this technology, in the future different modules for various applications can be developed and interconnected, depending on the required applications. In addition, this simple but rapid method of chip to chip connection overcomes potential problems associated with integrating incompatible materials on one device.

Journal Article↗

Principles of droplet electrohydrodynamics for lab-on-a-chip.

Electrically controlled droplet-based labs-on-a-chip operate under the principles of electro-capillarity and dielectrophoresis. The microfluidic mechanics of manipulating electrified droplets are complex and not entirely understood. In this article, we analyse these operating principles, especially electrowetting on dielectric (a form of electro-capillarity) and dielectrophoresis, under a unified framework of droplet electrohydrodynamics. We differentiate them by their electric origins and their energy transduction mechanisms. Our study shows that both electrowetting on dielectric and dielectrophoresis are effective for droplet generation and manipulation. In addition, our study demonstrates: (1) the presence of a wetting contribution to dielectrophoresis; and (2) contact angle reduction is merely an observable consequence of, not a condition for, the occurrence of electrowetting on dielectric. Simulations are used extensively in this article to illustrate device operation, to expose underlying physics, and to validate our conclusions. Simulations of electrically driven droplet generation, droplet translocation, droplet fusion, and droplet fission are presented.

Electrophoresis, Capillary↗

From DNA biosensors to gene chips.

Wide-scale DNA testing requires the development of small, fast and easy-to-use devices. This article describes the preparation, operation and applications of biosensors and gene chips, which provide fast, sensitive and selective detection of DNA hybridization. Various new strategies for DNA biosensors and gene chips are examined, along with recent trends and future directions. The integration of hybridization detection schemes with the sample preparation process in a 'Lab-on-a-Chip' format is also covered. While the use of DNA biosensors and gene chips is at an early stage, such devices are expected to have an enormous effect on future DNA diagnostics.

Biosensing Techniques↗

Microfluidic device reads up to four consecutive base pairs in DNA sequencing-by-synthesis.

We have developed the first fully integrated microfluidic system for DNA sequencing-by-synthesis. Using this chip and fluorescence detection, we have reliably sequenced up to 4 consecutive bps. The described sequencer can be integrated with other microfluidic components on the same chip to produce true lab-on-a-chip technology. The surface chemistry that was designed to anchor the DNA to elastomeric microchannels is useful in a broad range of studies and applications.

Base Pairing↗