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Showing papers on "Biochip published in 2005"


Journal ArticleDOI
TL;DR: Performing impedance-based detection at the microscale results in drastically reduced detection times for dilute bacterial samples, thanks to the ability to efficiently concentrate and capture the cells in an extremely small volume.
Abstract: Detection of a few live bacterial cells in many industrial or clinical samples is a very important technological problem. We have developed a microscale technique for concentrating bacterial cells from a dilute sample, by factors on the order of 10/sup 4/ to 10/sup 5/, and detecting their metabolic activity by purely electrical means. The technique was implemented on a silicon-based microfluidic chip where the cells are concentrated and incubated in a chamber with a volume of 400 pL. Concentration and capture are obtained by the use of dielectrophoresis on the bacterial cells, and metabolism detection is achieved by means of impedance measurements of the medium in which the bacteria are incubated. Performing impedance-based detection at the microscale results in drastically reduced detection times for dilute bacterial samples, thanks to the ability to efficiently concentrate and capture the cells in an extremely small volume. Such concentration eliminates the need to amplify the bacterial population by long culture steps. This detection technique can be used for a wide variety of applications.

173 citations


Journal ArticleDOI
TL;DR: Performance data from this automated biochip array analyzer provide evidence that it is now possible to produce stable and reproducible biochips for output of more than 2000 test results per hour.
Abstract: Background: Use of protein array technology over conventional assay methods has advantages that include simultaneous detection of multiple analytes, reduction in sample and reagent volumes, and high output of test results. The susceptibility of ligands to denaturation, however, has impeded production of a stable, reproducible biochip platform, limiting most array assays to manual or, at most, semiautomated processing techniques. Such limitations may be overcome by novel biochip fabrication procedures. Methods: After selection of a suitable biochip substrate, biochip surfaces were chemically modified and assessed to enable optimization of biochip fabrication procedures for different test panels. The assay procedure was then automated on a dedicated instrument, and assay performance was determined for a panel of cytokine markers. Assay results were then compared with a commercial method for measurement of cytokine markers. Results: Secondary ion mass spectrometry and x-ray photoelectron spectroscopy demonstrated appropriate and reproducible modification of the biochip surface. Contact-angle studies also confirmed generation of hydrophobic surfaces that enabled containment of droplets for fabrication of discrete test regions. Automation of the biochip assays on a dedicated instrument produced excellent cytokine marker performance with intra- and interassay imprecision <10% for most analytes. Comparison studies showed good agreement with other methods ( r = 0.95–0.99) for cytokines. Conclusion: Performance data from this automated biochip array analyzer provide evidence that it is now possible to produce stable and reproducible biochips for output of more than 2000 test results per hour.

171 citations


Proceedings ArticleDOI
13 Jun 2005
TL;DR: This work presents a synthesis methodology that unifies operation scheduling, resource binding, and module placement for such "digital" biochips and can also be used after fabrication to bypass defective cells in the microfluidic array.
Abstract: Microfluidic biochips promise to revolutionize biosensing and clinical diagnostics. As more bioassays are executed concurrently on a biochip, system integration and design complexity are expected to increase dramatically. This problem is also identified by the 2003 ITRS document as a major system-level design challenge beyond 2009. We focus here on the automated design of droplet-based microfluidic biochips. We present a synthesis methodology that unifies operation scheduling, resource binding, and module placement for such "digital" biochips. The proposed technique, which is based on parallel recombinative simulated annealing, can also be used after fabrication to bypass defective cells in the microfluidic array. A real-life protein assay is used to evaluate the synthesis methodology.

163 citations


Journal ArticleDOI
TL;DR: In this article, the authors present an overview of miniaturized biosensor devices based on the sensitive detection of magnetic nanoparticles using the giant magneto-resistance effect, which has advantages over established methods, and the sensitivity is promising.

151 citations


Journal ArticleDOI
TL;DR: The suitability of nucleic acid aptamers as low molecular weight receptors on biochips for sensitive and specific protein detection is shown, representing an innovative tool for future proteomics.
Abstract: The establishment of an aptamer-based biochip for protein detection is described. Using a model system comprising human IgE as the analyte and single-stranded DNA aptamers specific for IgE or anti-IgE antibodies as immobilized ligands on chips, we could demonstrate that aptamers were equivalent or superior to antibodies in terms of specificity and sensitivity, respectively. Aptamer-based analyte detection on glass slides could clearly be demonstrated at minimum concentrations of 10 ng/mL IgE. In addition, we successfully showed specific analyte recognition in complex protein samples by the aptamer-based biochip system. Using DNA aptamers specific for human thrombin as an additional model receptor/ligand system, dual protein detection on a single slide could be proven. In conclusion, we could show the suitability of nucleic acid aptamers as low molecular weight receptors on biochips for sensitive and specific protein detection, representing an innovative tool for future proteomics.

122 citations


Journal ArticleDOI
TL;DR: Fluorescence has been the preferred choice for data quantification in biomedical microarray formats since their earliest days as discussed by the authors, and as much diversity as on the microarrays themselves can be found at the detection device.
Abstract: Fluorescence has been the preferred choice for data quantification in biomedical microarray formats since their earliest days. As much as the formats have grown and evolved over the years, the methods in optical analysis have become ever more sophisticated and complex in order to produce more and better output. This review will provide an insight into the most common methods and the state-of-the-art of all areas in microarray fluorescence analysis. Starting with an overview on microarray formats with a focus on their demands on the readout, the most common and useful organic fluorescent stains are discussed before proceeding on to other approaches; the use of semiconductor nanocrystals (quantum dots), polymer and silica nanoparticles and fluorescent proteins. Ways to enhance the intrinsically low signal on biochips have become increasingly important as they offer a sound approach towards the detection of low concentration sample content. The three main categories are presented: amplification using DNA, enzymes, and dendrimers. As much diversity as on the microarrays themselves can be found at the detection device. Standard optical microarray detectors, and non-standard methods using fluorescence anisotropy, fluorescence lifetime imaging (FLIM) and fluorescence resonance energy transfer (FRET), and their advantages and disadvantages are discussed.

120 citations


Journal ArticleDOI
TL;DR: Different actuation mechanisms for microfluidics-based biochips, as well as associated design automation trends and challenges are presented, and the underlying physical principles of eletrokinetics, electrohydrodynamics, and thermo-capillarity are discussed.
Abstract: Advances in microfluidics technology offer exciting possibilities in the realm of enzymatic analysis, DNA analysis, proteomic analysis involving proteins and peptides, immunoassays, implantable drug delivery devices, and environmental toxicity monitoring. Microfluidics-based biochips are therefore gaining popularity for clinical diagnostics and other laboratory procedures involving molecular biology. As more bioassays are executed concurrently on a biochip, system integration and design complexity are expected to increase dramatically. This paper presents different actuation mechanisms for microfluidics-based biochips, as well as associated design automation trends and challenges. The underlying physical principles of eletrokinetics, electrohydrodynamics, and thermo-capillarity are discussed. Next, the paper presents an overview of an integrated system-level design methodology that attempts to address key issues in the modeling, simulation, synthesis, testing and reconfiguration of digital microfluidics-based biochips. The top-down design automation will facilitate the integration of fluidic components with microelectronic component in next-generation system-on-chip designs.

101 citations


Journal ArticleDOI
TL;DR: The microcontact printing can be considered as a new potential technology platform to pattern DNA microarrays that may have significant advantages over the conventional spotting technologies as it is easy to implement, it uses low cost material to make the stamp, and the arrays made by this technology are 10-times more sensitive in term of hybridization signals than those manufactured by conventional spotting technology.
Abstract: A critical step in the fabrication of biochips is the controlled placement of probes molecules on solid surfaces. This is currently performed by sequential deposition of probes on a target surface with split or solid pins. In this article, we present a cost-effective procedure namely microcontact printing using stamps, for a parallel deposition of probes applicable for manufacturing biochips. Contrary to a previous work, we showed that the stamps tailored with an elastomeric poly(dimethylsiloxane) material did not require any surface modification to be able to adsorb oligonucleotides or PCR products. The adsorbed DNA molecules are subsequently printed efficiently on a target surface with high sub-micron resolution. Secondly, we showed that successive stamping is characterized by an exponential decay of the amount of transferred DNA molecules to the surface up the 4th print, then followed by a second regime of transfer that was dependent on the contact time and which resulted in reduced quality of the features. Thus, while consecutive stamping was possible, this procedure turned out to be less reproducible and more time consuming than simply re-inking the stamps between each print. Thirdly, we showed that the hybridization signals on arrays made by microcontact printing were 5 to 10-times higher than those made by conventional spotting methods. Finally, we demonstrated the validity of this microcontact printing method in manufacturing oligonucleotides arrays for mutations recognition in a yeast gene. The microcontact printing can be considered as a new potential technology platform to pattern DNA microarrays that may have significant advantages over the conventional spotting technologies as it is easy to implement, it uses low cost material to make the stamp, and the arrays made by this technology are 10-times more sensitive in term of hybridization signals than those manufactured by conventional spotting technology.

101 citations


Journal ArticleDOI
TL;DR: In the emerging field of functional proteomics, protein microarrays are considered to be one of the most promising tools for the simultaneous analysis of the abundance, function, and interaction of proteins on a system-wide scale as discussed by the authors.
Abstract: In the emerging field of Functional Proteomics, protein microarrays are considered to be one of the most promising tools for the simultaneous analysis of the a) abundance, b) function, and c) interaction of proteins on a system-wide scale. Resting on the technological grounds of widely used DNA biochips, the great power of microarray-based miniature solid-phase immunoassays lies in their potential to investigate in parallel large numbers of analyte pairs in a variety of biological samples. Consequently, this has fueled aspirations that protein microarrays may serve as tools for the high-throughput functional investigation of complete proteomes and, moreover, that they will develop into promising candidates for innovative in-vitro diagnostic (IVD) applications. To date, published examples of protein microarrays for IVD purposes have included tests for allergy, autoimmune and infectious diseases. Here, we discuss recent advancements in the development of protein microarrays for the profiling of IgE antibodies in the diagnosis of Type 1-related allergic diseases.

96 citations


Journal ArticleDOI
TL;DR: Experimental results and finite element modeling of the holding forces for both positive and negative dielectrophoretic traps on microfabricated interdigitated electrodes within a microfluidic biochip fabricated in silicon with a 12-/spl mu/m-deep chamber validating the ability to model the dielectrophic filter for bacteria, spores, yeast cells, and polystyrene beads.
Abstract: Microfabricated interdigitated electrode array is a convenient form of electrode geometry for dielectrophoretic trapping of particles and biological entities such as cells and bacteria within microfluidic biochips. We present experimental results and finite element modeling of the holding forces for both positive and negative dielectrophoretic traps on microfabricated interdigitated electrodes within a microfluidic biochip fabricated in silicon with a 12-/spl mu/m-deep chamber. Anodic bonding was used to close the channels with a glass cover. An Experimental protocol was then used to measure the voltages necessary to capture different particles (polystyrene beads, yeast cells, spores and bacteria) against destabilizing fluid flows at a given frequency. The experimental results and those from modeling are found to be in close agreement, validating our ability to model the dielectrophoretic filter for bacteria, spores, yeast cells, and polystyrene beads. This knowledge can be very useful in designing and operating a dielectrophoretic barrier or filter to sort and select particles entering the microfluidic devices for further analysis.

93 citations


Journal ArticleDOI
TL;DR: The ability to detect one mutant DNA in 100 normal sequences with the biochip assembly is successfully demonstrated, and the hybridization time significantly reduced through enhanced mass transport to the surface-tethered zip code probes.
Abstract: We have fabricated a flow-through biochip assembly that consisted of two different microchips: (1) a polycarbonate (PC) chip for performing an allele-specific ligation detection reaction (LDR) and (2) a poly(methyl methacrylate) (PMMA) chip for the detection of the LDR products using an universal array platform. The operation of the device was demonstrated by detecting low-abundant DNA mutations in gene fragments (K-ras) that carry point mutations with high diagnostic value for colorectal cancers. The PC microchip was used for the LDR in a continuous-flow format, in which two primers (discriminating primer that carried the complement base to the mutation being interrogated and a common primer) that flanked the point mutation and were ligated only when the particular mutation was present in the genomic DNA. The miniaturized reactor architecture allowed enhanced reaction speed due to its high surface-to-volume ratio and efficient thermal management capabilities. A PMMA chip was employed as the microarray d...

Journal ArticleDOI
TL;DR: Current trends and advances in miniaturized multiplexed immunoassay technologies are presented, reviewing different systems from research to point-of-care assays and focusing on a subset of chip-based assays that may be used in a clinical laboratory and are directly applicable for biomedical diagnosis.
Abstract: Classical methods of protein analysis such as electrophoresis, ELISA and liquid chromatography are generally time-consuming, labor-intensive and lack high-throughput capacity. In addition, all existing methods used to measure proteins necessitate multiple division of the original sample and individual tests carried out for each substance, with an associated cost for each test. The chip system allows several tests to be performed simultaneously without dividing the original patient sample. This system facilitates the development of multiplexed assays that simultaneously measure many different analytes in a small sample volume. These emerging technologies fall into two categories: 1) spotted array-based tools, and 2) microfluidic-based tools. Miniaturized and multiplexed immunoassays allow a great deal of information to be obtained from a single sample. These analytical systems are referred to as "lab-on-a-chip" devices. This article presents current trends and advances in miniaturized multiplexed immunoassay technologies, reviewing different systems from research to point-of-care assays. We focus on a subset of chip-based assays that may be used in a clinical laboratory and are directly applicable for biomedical diagnosis. Recent advances in biochip assays combine the power of miniaturization, microfluidics, micro- to nanoparticles, and quantification. A number of applications are just beginning to be explored. The power of biochip assays offers great promise for point-of-care clinical testing and monitoring of many important analytes.

Journal ArticleDOI
TL;DR: Control processes employed in the manufacture and analysis of Evidence components ensure reproducibility of assays for a range of routine and novel markers.
Abstract: Background: Proteomics’ requirement for simultaneous measurement of multiple markers is now possible with biochip array technology. Many laboratories utilise in-house, manual procedures for biochip fabrication and sample testing. Reproducibility and standardisation of biochip processes is vital to ensure quality of results and offer the best tool for elucidation of complex relationships between multiple proteins in diseased conditions. Methods: Various novel control checks have been implemented in biochip fabrication, reagent manufacture, automation and imaging processes for the Evidence analyser. Reference spots enable location of discrete test regions on the surface of the biochip and simultaneous quantification of multiple markers. Performance and standardisation methods are presented. Results: Formulation of dispense solution for discrete test regions had a direct effect on their shape, stability and integrity on the biochip surface. Assays for fertility hormones and drugs of abuse demonstrated excellent precision, stability and comparison with other commercial methods. Conclusion: Control processes employed in the manufacture and analysis of Evidence components ensures reproducibility of assays for a range of routine and novel markers. Abbreviations: SNPs, single nucleotide polymorphisms; 2-D PAGE, two-dimensional polyacrylamide gel electrophoresis; SELDI, surface-enhanced laser desorption and ionization; DTR, discrete test region; RLU, Relative Light Units; ABM, automatic biochip micrometer; QC, Quality Control; CCD, Charge Coupled Device; HRP, horseradish peroxidase; LIMS, laboratory information management systems; GC-MS, Gas Chromatography-Mass Spectrometery; FSH, Follice Stimulating Hormone; LH, Luteinising Hormone

Proceedings ArticleDOI
07 Mar 2005
TL;DR: Spare cells are placed in the interstitial sites within the microfluidic array, and they replace neighboring faulty cells via local reconfiguration to enhance the yield of biochips that are based on droplet-based microfluidity.
Abstract: As microfluidics-based biochips become more complex, manufacturing yield will have significant influence on production volume and product cost. We propose an interstitial redundancy approach to enhance the yield of biochips that are based on droplet-based microfluidics. In this design method, spare cells are placed in the interstitial sites within the microfluidic array, and they replace neighboring faulty cells via local reconfiguration. The proposed design method is evaluated using a set of concurrent real-life bioassays.

Proceedings ArticleDOI
03 Jan 2005
TL;DR: A clinical diagnostic procedure, namely multiplexed in-vitro diagnostics on human physiological fluids, is used to illustrate the design approach and a discussion of fault models, catastrophic fault testing, and concurrent test issues are included.
Abstract: Microfluidics-based biochips offer a promising platform for massively parallel DNA analysis, automated drug discovery, and real-time biomolecular recognition. The first part of this paper introduces readers to digital microfluidics technology. The second part describes a recent technique for the automated design and synthesis of biochips. A clinical diagnostic procedure, namely multiplexed in-vitro diagnostics on human physiological fluids, is used to illustrate the design approach. The third part of the embedded tutorial is focused on test issues. It is important to ensure high reliability and availability of biochips as they are increasingly deployed for safety-critical applications. The tutorial includes a discussion of fault models, catastrophic fault testing, and concurrent test issues.

Journal ArticleDOI
TL;DR: A portable biochip system based on complementary metal oxide semiconductor (CMOS) technology that has great potential as a device for single-bacteria detection and the possibility of single-Bacteria detection is reported using an immunoassay coupled to laser-induced fluorescence (LIF) detection.

Journal ArticleDOI
TL;DR: A biochip approach based on porous silicon as substrate is presented to enhance the sensitivity of the biochip by increasing the specific surface area on the support and radioactive measurements show a 10-fold enhancement of the oligonucleotide surface density on the porous silicon substrate.

01 Jan 2005
TL;DR: The proposed topdown design automation approach is expected to relieve biochip users from the burden of manual optimization of bioassays, time-consuming hardware design, and costly testing and maintenance procedures.
Abstract: Microfluidics-based biochips are soon expected to revolutionize clinical diagnosis, DNA sequencing, and other laboratory procedures involving molecular biology. As more bioassays are executed concurrently on a biochip, system integration and design complexity are expected to increase dramatically. Current techniques for full-custom design of digital microfluidic biochips however do not scale well for concurrent assays and for next-generation systemon-chip (SOC) designs that are expected to include fluidic components. We present here an overview of an integrated system-level design methodology that attempts to address key issues in the synthesis, testing and reconfiguration of digital microfluidics-based biochips. The proposed topdown design automation approach is expected to relieve biochip users from the burden of manual optimization of bioassays, time-consuming hardware design, and costly testing and maintenance procedures.

Proceedings ArticleDOI
08 Nov 2005
TL;DR: This work presents a testing and diagnosis methodology to detect catastrophic faults and locate faulty regions, and is evaluated using a biochip performing real-life multiplexed bioassays
Abstract: Microfluidics-based biochips are soon expected to revolutionize biosensing, clinical diagnostics and drug discovery. Robust off-line and on-line test techniques are required to ensure system dependability as these biochips are deployed for safety-critical applications. Due to the underlying mixed-technology and mixed-energy domains, biochips exhibit unique failure mechanisms and defects. We first relate some realistic defects to fault models and observable errors. We next set up an experiment to evaluate the manifestations of electrode-short faults. Motivated by the experimental results, we present a testing and diagnosis methodology to detect catastrophic faults and locate faulty regions. The proposed method is evaluated using a biochip performing real-life multiplexed bioassays

Proceedings ArticleDOI
07 Mar 2005
TL;DR: This work presents a simulated annealing-based technique for module placement in "digital" droplet-based microfluidic biochips, and considers fault tolerance, which allows a micro fluidic module to be relocated elsewhere in the system when a single cell is detected to be faulty.
Abstract: Microfluidics-based biochips are soon expected to revolutionize clinical diagnosis, DNA sequencing, and other laboratory procedures involving molecular biology. Most microfluidic biochips are based on the principle of continuous fluid flow and they rely on permanently-etched microchannels, micropumps, and microvalves. We focus here on the automated design of "digital" droplet-based microfluidic biochips. In contrast to continuous-flow systems, digital microfluidics offers dynamic reconfigurability; groups of cells in a microfluidics array can be reconfigured to change their functionality during the concurrent execution of a set of bioassays. We present a simulated annealing-based technique for module placement in such biochips. The placement procedure not only addresses chip area, but it also considers fault tolerance, which allows a microfluidic module to be relocated elsewhere in the system when a single cell is detected to be faulty. Simulation results are presented for a case study involving the polymerase chain reaction.

Patent
05 Jul 2005
TL;DR: In this paper, the authors present a set of biochips for the measurement of cellular ion channels and methods of use and manufacture, which have enhanced sealing capabilities provided in part by chemically modifying the surface of the biochip surface or substrate or by exposure to ionized gas.
Abstract: The present invention includes biochips for the measurement of cellular ion channels and methods of use and manufacture. The biochips of the present invention have enhanced sealing capabilities provided in part by chemically modifying the surface of the biochip surface or substrate or by exposure to an ionized gas. The present invention also includes novel cartridges for biochips.

Journal ArticleDOI
01 Sep 2005-Methods
TL;DR: The microfabrication and operational characteristics of a simple flow-through biochip sensor capable of detecting low abundant point mutations in K-ras oncogenes from genomic DNA, which carry high diagnostic value for colorectal cancers are described.

Journal ArticleDOI
TL;DR: In this article, a microarray of nine screen-printed graphite electrodes was used to develop multi-parametric electrochemiluminescent (ECL) biochip, which is based on the ECL detection of enzymatically generated H 2 O 2.

Journal ArticleDOI
04 Apr 2005
TL;DR: Results show a discernable difference in sensor response after washing when using complementary or non-complementary DNA targets, and it was observed that hybridization signals decreased slightly after the more stringent wash indicating that non-specifically or weakly bound labels were washed away.
Abstract: Over the past few years the concept of using magnetic field sensors for biological applications in particular, the development of magnetoresistive biochips and biosensors, has generated increasing interest from laboratories and companies. A spin-valve sensor based biochip was used to detect cystic fibrosis related DNA targets for the purpose of developing an affordable diagnostic chip and detection system. The strategy is based on the AC magnetic field focusing technique. This method consists of the attraction, concentration and manipulation of magnetically-labelled target DNA within on-chip u-shaped current line regions surface functionalized with a cystic fibrosis-related DNA probe. Cystic fibrosis related probes were immobilized on the oxide surface and 250 nm diameter non-remanent magnetic particles were functionalized with cystic fibrosis related DNA targets complementary or non-complementary to the immobilized probes. The hybridization of the target is detected using a u-shaped spin-valve sensor fabricated within the line structure. The proximity of probe and target at the spin-valve sensor surface promotes the hybridization of complementary DNA strands. In this way, hybridization occurs in relatively short times, (5-25 minutes), in comparison with conventional hybridization approaches (3 to 12 hours), as limited by diffusion of the target DNA in solution. Magnetic labels bound to the sensor surface through the hybridization of complementary DNA strands have a magnetic stray field that changes the resistance of sensors enabling detection of the hybridization in real-time. Results show a discernable difference in sensor response after washing when using complementary or non-complementary DNA targets. The use of complementary target DNA resulted in distinct hybridization signals and the binding of the particles in the sensor area was verified by visual inspection. In addition, it was observed that hybridization signals decreased slightly after the more stringent wash indicating that non-specifically or weakly bound labels were washed away. The use of non-complementary target DNA resulted in negligible sensor response after washing and no particles were observed in the sensor area.

Journal ArticleDOI
TL;DR: In this minireview, different types of chip reactors for biotechnological applications like nanotiterplates, chip thermocyclers and devices for segmented flow operations are discussed and an outlook is given on the application of chip reactor systems.
Abstract: Chip devices were introduced in chemistry and molecular biology to improve the read-out of information from molecular systems by efficient analytical procedures and to organize automated experiments. Biochips and chip reactor systems are of interest for cellular processes, too, and can be regarded as components in interfaces for the information exchange between living nature and digital electronic systems. In this minireview, different types of chip reactors for biotechnological applications like nanotiterplates, chip thermocyclers and devices for segmented flow operations are discussed. Finally, an outlook is given on the application of chip reactor systems, which are promising tools for automated experiments with highly parallelized screening procedures, for artificial microcompartmentation, cell analogue systems, micro-ecological studies, investigations on modulated morphogenesis, and for a bioanalogue molecular nanotechnology.

Journal ArticleDOI
TL;DR: It is demonstrated that the phase transition of the lipidic layer can modulate the dynamic of the association of the complex to the supported membrane, and feature unique properties including tunable surface density of probes, very low non-specific interactions and optimization of hybridization efficiency.

Proceedings ArticleDOI
05 Jun 2005
TL;DR: In this paper, a method for measuring the effective refractive index (RI) of a single living cell with a small integrated chip is presented, which is able to determine the RI of living cell in real time without extra requirements of fluorescence labeling and chemical treatments, offering low cost and high accuracy meanwhile.
Abstract: This paper reports a novel method for measuring the effective refractive index (RI) of single living cell with a small integrated chip. This microchip is able to determine the RI of living cell in real time without extra requirements of fluorescence labeling and chemical treatments, offering low cost and high accuracy meanwhile. It might provide an efficient approach for diseases or cancer diagnosis. The measurement system integrates laser diode, microlenses, and microfluidic channels onto a monolithic chip. In the experiments, two standard polystyrene beads with nominal RIs are, employed to calibrate the system and five types of cancerous cells are subsequently measured. The results indicate that the RI of the tested cells ranges from 1.392 to 1.401, which is larger than typical value 1.35-1.37 for normal cells.

Journal ArticleDOI
Yan Weiping1, Du Liqun1, Wang Jing1, Ma Lingzhi1, Zhu Jianbo1 
TL;DR: In this paper, a micro PCR biochip based on silicon is designed and fabricated by MEMS technology in order to reduce the processing complicacy, the temperature sensor and the micro heater were fabricated with chromium metal film.
Abstract: PCR technology has been widely applied to biomedicine and other related fields. PCR biochip shortens reaction time and reduces expensive reagents quantities. If the PCR biochip can be integrated with capillary electrophoresis chip, then the microminiaturization of biochemical analysis system will be possible. A micro PCR biochip based on silicon is designed and fabricated by MEMS technology in this paper. In order to reduce the processing complicacy, the temperature sensor and the micro heater were fabricated with chromium metal film. Since the characteristics of metal membrane is closely related to the performance of the material itself and the fabrication technology, the impact of fabrication technology on the membrane performance is studied in this paper. The results indicate the rational domain design, suitable processing condition and appropriate controlling system are preferable to the requirements of PCR reaction.

Journal ArticleDOI
TL;DR: The CNTFET-based biochip is a promising candidate for the development of an integrated, high-throughput, portable device for nucleic acid-based diagnostics.
Abstract: We have developed a nanosensor array composed of carbon nanotube field-effect transistors (CNTFETs) on SiO2/Si substrates. Unlike previously reported CNTFETs where the recognition event occurred directly on the CNT, in this case, the reverse surface of the substrate was utilized for the biomolecular functionalization. A self-assembled monolayer (SAM) of peptide nucleic acid (PNA) probes associated with the tumor necrosis factor-α gene (TNF-α) was attached onto the gold electrode on the reverse side of the CNTFET device. A time-dependent conductance increase was monitored upon sequential introduction of wild-type (WT) DNA samples through a microfluidic channel of the poly(dimethylsiloxane) (PDMS) chip. High selectivity of PNA probes only toward the full-complementary WT DNA samples enabled rapid and simple discrimination against single-nucleotide polymorphism (SNP) or non-complementary (NC) DNA. Concentration-dependent measurements indicated a limit-of-detection (LOD) of 6.8 fM WT DNA. Our CNTFET-based biochip is a promising candidate for the development of an integrated, high-throughput, portable device for nucleic acid-based diagnostics.

Patent
05 Jul 2005
TL;DR: A biochip (100) for lysing and/or cell separation is formed to provide a sealed chamber for biological fluid as discussed by the authors, and a conductive layer (140) bonded between upper (130) and lower (150) insulating layers is etched to form a microfluidic channel (250) between two electrodes (190, 200) to generate a dielectrophoretic force on the cells/particles within the sample fluid.
Abstract: A biochip (100) for lysing and/or cell separation is formed to provide a sealed chamber for biological fluid A conductive layer (140) bonded between upper (130) and lower (150) insulating layers is etched to form a microfluidic channel (250) between two electrodes (190, 200) The microfluidic channel connects a fluid inlet (11) and fluid outlet (120) The electrodes (190, 200) form an un-even electric field in the channel (250) to generate a dielectrophoretic force on the cells/particles within the sample fluid A voltage source applies a suitable voltage to separate and/or lyse cells within the fluid