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At least 217 records · Page 12Linked to original sources

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↗

Adaptive liquid microlenses activated by stimuli-responsive hydrogels.

Despite its compactness, the human eye can easily focus on different distances by adjusting the shape of its lens with the help of ciliary muscles. In contrast, traditional man-made optical systems achieve focusing by physical displacement of the lenses used. But in recent years, advances in miniaturization technology have led to optical systems that no longer require complicated mechanical systems to tune and adjust optical performance. These systems have found wide use in photonics, displays and biomedical systems. They are either based on arrays of microlenses with fixed focal lengths, or use external control to adjust the microlens focal length. An intriguing example is the tunable liquid lens, where electrowetting or external pressure manipulates the shape of a liquid droplet and thereby adjusts its optical properties. Here we demonstrate a liquid lens system that allows for autonomous focusing. The central component is a stimuli-responsive hydrogel integrated into a microfluidic system and serving as the container for a liquid droplet, with the hydrogel simultaneously sensing the presence of stimuli and actuating adjustments to the shape--and hence focal length--of the droplet. By working at the micrometre scale where ionic diffusion and surface tension scale favourably, we can use pinned liquid-liquid interfaces to obtain stable devices and realize response times of ten to a few tens of seconds. The microlenses, which can have a focal length ranging from -infinity to +infinity (divergent and convergent), are also readily integrated into arrays that may find use in applications such as sensing, medical diagnostics and lab-on-a-chip technologies.

Biomedical Engineering↗

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↗

Biomimetic design of microfluidic manifolds based on a generalised Murray's law.

The relationship governing the optimum ratio between the diameters of the parent and daughter branches in vascular systems was first discovered by Murray using the principle of minimum work. This relationship is now known as Murray's law and states that the cube of the diameter of the parent vessel must equal the sum of the cubes of the daughter vessels. For symmetric bifurcations, an important consequence of this geometric rule is that the tangential shear stress at the wall remains constant throughout the vascular network. In the present paper, we extend this important hydrodynamic concept to arbitrary cross-sections and provide a framework for constructing a simple but elegant biomimetic design rule for hierarchical microfluidic networks. The paper focuses specifically on constant-depth rectangular and trapezoidal channels often employed in lab-on-a-chip systems. To validate our biomimetic design rule and demonstrate the application of Murray's law to microfluidic manifolds, a comprehensive series of computational fluid dynamics simulations have been performed. The numerical predictions are shown to be in very good agreement with the theoretical analysis, confirming that the generalised version of Murray's law can be successfully applied to the design of constant-depth microfluidic devices.

Biomimetics↗

Application of electrokinetic instability flow for enhanced micromixing in cross-shaped microchannel.

This paper proposes a cross-shaped micromixer featuring a pair barrier within the mixing channel. The proposed device obtains a rapid mixing of two sample fluids by means of the electrokinetic instability-induced shedding effects which are produced when a DC electric field of an appropriate intensity is applied. The proposed device uses a single high-voltage power source to simultaneously drive and mix the sample fluids. The effectiveness of the mixer is characterized experimentally as a function of the applied electric field intensity and the extent to which a pair barrier obstruct the mixing channel. The experimental results indicate that the mixing performance reaches 96% at a cross-section located 1 mm downstream of the cross-junction when an electric field of 300 V/cm is applied. The micromixing method presented in this study provides a simple low-cost solution to mixing problems in lab-on-a-chip systems.

Kinetics↗

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↗

Fabrication of a glass capillary electrophoresis microchip with integrated electrodes.

In this chapter, a detailed outline delineating the processing steps for microfabricating capillary electrophoresis (CE) with integrated electrochemical detection (ECD) platforms for performing analyte separation and detection is presented to enable persons familiar with microfabrication to enter a cleanroom and fabricate a fully functional Lab-on-a-Chip (LOC) microdevice. The processing steps outlined are appropriate for the production of LOC prototypes using easily obtained glass substrates and common microfabrication techniques. Microfabrication provides a major advantage over existing macro-scale systems by enabling precise control over electrode placement, and integration of all required CE and ECD electrodes directly onto a single substrate with a small footprint. In the processing sequences presented, top and bottom glass substrates are photolithographically patterned and etched using wet chemical processing techniques. The bottom substrate contains seven electrodes required for CE/ECD operation, whereas the top substrate contains the microchannel network. The flush planar electrodes are created using sputter deposition and lift-off processing techniques. Finally, the two glass substrates are thermally bonded to create the final LOC device.

Electrochemistry↗

Pore architecture of diatom frustules: potential nanostructured membranes for molecular and particle separations.

Diatoms produce diverse three-dimensional regular silica structures with nanometer to micrometer dimensions and hold considerable promise for biological and biomimetic fabrication of nanostructured materials and devices. In the present work, we describe the ultrastructural characterization of porous structures in diatom biosilica and discuss their potential as membrane filters for diffusion based separations. The frustules of two centric diatom species, Coscinodiscus sp. and Thalassiosira eccentrica, were investigated using scanning electron microscopy and atomic force microscopy. Their morphological features, including pore size, shape, porosity, and pore organization, are described. We observed that although pore organization in frustules of Thalassiosira eccentrica and Coscinodiscus sp. is in reverse order, a striking commonality is the size range of the smallest pores in both species (around 40 nm). The consensus lower pore size suggests that frustule valves have a common function at this size of excluding viruses or other deleterious particles, and the pore size and organization is optimized for this purpose. We suggest and implement an experimental approach to study the potential of diatom frustules for diffusive separation of molecular or nanoparticular components in microfluidic or lab-on-a-chip environments.

Animals↗

Integrated polymerase chain reaction chips utilizing digital microfluidics.

This study reports an integrated microfluidic chip for polymerase chain reaction (PCR) applications utilizing digital microfluidic chip (DMC) technology. Several crucial procedures including sample transportation, mixing, and DNA amplification were performed on the integrated chip using electro-wetting-on-dielectric (EWOD) effect. An innovative concept of hydrophobic/hydrophilic structure has been successfully demonstrated to integrate the DMC chip with the on-chip PCR device. Sample droplets were generated, transported and mixed by the EWOD-actuation. Then the mixture droplets were transported to a PCR chamber by utilizing the hydrophilic/hydrophobic interface to generate required surface tension gradient. A micro temperature sensor and two micro heaters inside the PCR chamber along with a controller were used to form a micro temperature control module, which could perform precise PCR thermal cycling for DNA amplification. In order to demonstrate the performance of the integrated DMC/PCR chips, a detection gene for Dengue II virus was successfully amplified and detected. The new integrated DMC/PCR chips only required an operation voltage of 12V(RMS) at a frequency of 3 KHz for digital microfluidic actuation and 9V(DC) for thermal cycling. When compared to its large-scale counterparts for DNA amplification, the developed system consumed less sample and reagent and could reduce the detection time. The developed chips successfully demonstrated the feasibility of Lab-On-a-Chip (LOC) by utilizing EWOD-based digital microfluidics.

Dengue Virus↗

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↗

Magnetic particles as markers and carriers of biomolecules.

The detection and manipulation of biomolecules on a common platform is of considerable interest not only for application in devices such as diagnostic tools but also for basic research in biological and medical systems. A promising approach is the utilisation of magnetic particles as markers and carriers for biomolecules. The principle functionality of this approach is demonstrated by the authors. Magnetic particles used as markers can be detected by highly sensitive magnetoresistive sensors resulting in a purely electronic signal. A direct comparison with the standard fluorescence method reveals the advantages of using the magnetic particles. In addition, magnetic particles used as carriers can be manipulated on-chip via currents running through especially designed line patterns. Some current drawbacks and future aspects are discussed. The combination of sensing and manipulating magnetic particles is a promising choice for future integrated lab-on-a-chip systems.

Biomarkers↗

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↗