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Автор: Grafiati

Опубліковано: 6 вересня 2023

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1

Munro, Nicole J., Karen Snow, Jeffrey A. Kant, and James P. Landers. "Molecular Diagnostics on Microfabricated Electrophoretic Devices: From Slab Gel- to Capillary- to Microchip-based Assays for T- and B-Cell Lymphoproliferative Disorders." Clinical Chemistry 45, no. 11 (November 1, 1999): 1906–17. http://dx.doi.org/10.1093/clinchem/45.11.1906.

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Abstract Background: Current methods for molecular-based diagnosis of disease rely heavily on modern molecular biology techniques for interrogating the genome for aberrant DNA sequences. These techniques typically include amplification of the target DNA sequences followed by separation of the amplified fragments by slab gel electrophoresis. As a result of the labor-intensive, time-consuming nature of slab gel electrophoresis, alternative electrophoretic formats have been developed in the form of capillary electrophoresis and, more recently, multichannel microchip electrophoresis. Methods: Capillary electrophoresis was explored as an alternative to slab gel electrophoresis for the analysis of PCR-amplified products indicative of T- and B-cell malignancies as a means of defining the elements for silica microchip-based diagnosis. Capillary-based separations were replicated on electrophoretic microchips. Results: The microchip-based electrophoretic separation effectively resolved PCR-amplified fragments from the variable region of the T-cell receptor-γ gene (150–250 bp range) and the immunoglobulin heavy chain gene (80–140 bp range), yielding diagnostically relevant information regarding the presence of clonal DNA populations. Although hydroxyethylcellulose provided adequate separation power, the need for a coated microchannel for effective resolution necessitated additional preparative steps. In addition, preliminary data are shown indicating that polyvinylpyrrolidone may provide an adequate matrix without the need for microchannel coating. Conclusions: Separation of B- and T-cell gene rearrangement PCR products on microchips provides diagnostic information in dramatically reduced time (160 s vs 2.5 h) with no loss of diagnostic capacity when compared with current methodologies. As illustrated, this technology and methodology holds great potential for extrapolation to the abundance of similar molecular biology-based techniques.

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2

Ha, Ji Won. "Acupuncture Injection Combined with Electrokinetic Injection for Polydimethylsiloxane Microfluidic Devices." Journal of Analytical Methods in Chemistry 2017 (2017): 1–6. http://dx.doi.org/10.1155/2017/7495348.

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We recently reported acupuncture sample injection that leads to reproducible injection of nL-scale sample segments into a polydimethylsiloxane (PDMS) microchannel for microchip capillary electrophoresis. The advantages of the acupuncture injection in microchip capillary electrophoresis include capability of minimizing sample loss and voltage control hardware and capability of introducing sample plugs into any desired position of a microchannel. However, the challenge in the previous study was to achieve reproducible, pL-scale sample injections into PDMS microchannels. In the present study, we introduce an acupuncture injection technique combined with electrokinetic injection (AICEI) technique to inject pL-scale sample segments for microchip capillary electrophoresis. We carried out the capillary zone electrophoresis (CZE) separation of FITC and fluorescein, and the mixture of 10 μM FITC and 10 μM fluorescein was separated completely by using the AICEI method.

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3

Fister, Julius C., Stephen C. Jacobson, and J. Michael Ramsey. "Ultrasensitive Cross-Correlation Electrophoresis on Microchip Devices." Analytical Chemistry 71, no. 20 (October 1999): 4460–64. http://dx.doi.org/10.1021/ac990853d.

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4

Chen, Yu-Hung, Wei-Chang Wang, Kung-Chia Young, Ting-Tsung Chang, and Shu-Hui Chen. "Plastic Microchip Electrophoresis for Analysis of PCR Products of Hepatitis C Virus." Clinical Chemistry 45, no. 11 (November 1, 1999): 1938–43. http://dx.doi.org/10.1093/clinchem/45.11.1938.

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Abstract Background: Electrophoresis on polymeric rather than glass microstructures is a promising separation method for analytical chemistry. Assays on such devices need to be explored to allow assessment of their utility for the clinical laboratory. Methods: We compared capillary and plastic microchip electrophoresis for clinical post-PCR analysis of hepatitis C virus (HCV). For capillary electrophoresis (CE), we used a separation medium composed of 10 g/L hydroxypropyl methyl cellulose in Tris-borate-EDTA buffer and 10 μmol/L intercalating dye. For microchip electrophoresis, the HCV assay established on the fused silica tubing was transferred to the untreated polymethylmethacrylate microchip with minimum modifications. Results: CE resolved the 145-bp amplicon of HCV in 15 min. The confidence interval of the migration time was <3.2%. The same HCV amplicon was resolved by microchip electrophoresis in <1.5 min with the confidence interval of the migration time <1.3%. Conclusion: The polymer microchip, with advantages that include fast processing time, simple operation, and disposable use, holds great potential for clinical analysis.

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5

Rodríguez, Isabel, Lian Ji Jin, and Sam F. Y. Li. "High-speed chiral separations on microchip electrophoresis devices." Electrophoresis 21, no. 1 (January 1, 2000): 211–19. http://dx.doi.org/10.1002/(sici)1522-2683(20000101)21:1<211::aid-elps211>3.0.co;2-d.

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6

Kumar, Suresh, Vishal Sahore, Chad I. Rogers, and Adam T. Woolley. "Development of an integrated microfluidic solid-phase extraction and electrophoresis device." Analyst 141, no. 5 (2016): 1660–68. http://dx.doi.org/10.1039/c5an02352a.

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7

Vrouwe, Elwin X., Regina Luttge, Istvan Vermes, and Albert van den Berg. "Microchip Capillary Electrophoresis for Point-of-Care Analysis of Lithium." Clinical Chemistry 53, no. 1 (January 1, 2007): 117–23. http://dx.doi.org/10.1373/clinchem.2007.073726.

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Abstract Background: Microchip capillary electrophoresis (CE) is a promising method for chemical analysis of complex samples such as whole blood. We evaluated the method for point-of-care testing of lithium. Methods: Chemical separation was performed on standard glass microchip CE devices with a conductivity detector as described in previous work. Here we demonstrate a new sample-to-chip interface. Initially, we took a glass capillary as a sample collector for whole blood from a finger stick. In addition, we designed a novel disposable sample collector and tested it against the clinical standard at the hospital (Medisch Spectrum Twente). Both types of collectors require <10 μL of test fluid. The collectors contain an integrated filter membrane, which prevents the transfer of blood cells into the microchip. The combination of such a sample collector with microchip CE allows point-of-care measurements without the need for off-chip sample treatment. This new on-chip protocol was verified against routine lithium testing of 5 patients in the hospital. Results: Sodium, lithium, magnesium, and calcium were separated in <20 s. The detection limit for lithium was 0.15 mmol/L. Conclusions: The new microchip CE system provides a convenient and rapid method for point-of-care testing of electrolytes in serum and whole blood.

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8

Ludwig, Martin, and Detlev Belder. "Coated microfluidic devices for improved chiral separations in microchip electrophoresis." ELECTROPHORESIS 24, no. 15 (August 2003): 2481–86. http://dx.doi.org/10.1002/elps.200305498.

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9

Kricka, Larry J. "Miniaturization of analytical systems." Clinical Chemistry 44, no. 9 (September 1, 1998): 2008–14. http://dx.doi.org/10.1093/clinchem/44.9.2008.

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Abstract Miniaturization has been a long-term trend in clinical diagnostics instrumentation. Now a range of new technologies, including micromachining and molecular self-assembly, are providing the means for further size reduction of analyzers to devices with micro- to nanometer dimensions and submicroliter volumes. Many analytical techniques (e.g., mass spectrometry and electrophoresis) have been successfully implemented on microchips made from silicon, glass, or plastic. The new impetus for miniaturization stems from the perceived benefits of faster, easier, less costly, and more convenient analyses and by the needs of the pharmaceutical industry for microscale, massively parallel drug discovery assays. Perfecting a user-friendly interface between a human and a microchip and determining the realistic lower limit for sample volume are key issues in the future implementation of these devices. Resolution of these issues will be important for the long-term success of microminiature analyzers; in the meantime, the scope, diversity, and rate of progress in the development of these devices promises products in the near future.

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10

Gibson, Larry R., and Paul W. Bohn. "Non-aqueous microchip electrophoresis for characterization of lipid biomarkers." Interface Focus 3, no. 3 (June 6, 2013): 20120096. http://dx.doi.org/10.1098/rsfs.2012.0096.

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In vivo measurements of lipid biomarkers are hampered by their low solubility in aqueous solution, which limits the choices for molecular separations. Here, we introduce non-aqueous microchip electrophoretic separations of lipid mixtures performed in three-dimensional hybrid nanofluidic/microfluidic polymeric devices. Electrokinetic injection is used to reproducibly introduce discrete femtolitre to picolitre volumes of charged lipids into a separation microchannel containing low (100 μM–10 mM) concentration tetraalkylammonium tetraphenylborate background electrolyte (BGE) in N -methylformamide, supporting rapid electro-osmotic fluid flow in polydimethylsiloxane microchannels. The quality of the resulting electrophoretic separations depends on the voltage and timing of the injection pulse, the BGE concentration and the electric field strength. Injected volumes increase with longer injection pulse widths and higher injection pulse amplitudes. Separation efficiency, as measured by total plate number, N , increases with increasing electric field and with decreasing BGE concentration. Electrophoretic separations of binary and ternary lipid mixtures were achieved with high resolution ( R s ∼ 5) and quality ( N > 7.7 × 10 6 plates m −1 ). Rapid in vivo monitoring of lipid biomarkers requires high-quality separation and detection of lipids downstream of microdialysis sample collection, and the multilayered non-aqueous microfluidic devices studied here offer one possible avenue to swiftly process complex lipid samples. The resulting capability may make it possible to correlate oxidative stress with in vivo lipid biomarker levels.

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11

Belder, Detlev, Alfred Deege, Frank Kohler, and Martin Ludwig. "Poly(vinyl alcohol)-coated microfluidic devices for high-performance microchip electrophoresis." ELECTROPHORESIS 23, no. 20 (October 2002): 3567–73. http://dx.doi.org/10.1002/1522-2683(200210)23:20<3567::aid-elps3567>3.0.co;2-3.

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12

Beauchamp, Michael J., Anna V. Nielsen, Hua Gong, Gregory P. Nordin, and Adam T. Woolley. "3D Printed Microfluidic Devices for Microchip Electrophoresis of Preterm Birth Biomarkers." Analytical Chemistry 91, no. 11 (May 6, 2019): 7418–25. http://dx.doi.org/10.1021/acs.analchem.9b01395.

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13

Ghanim, M. H., and M. Z. Abdullah. "Integrating amperometric detection with electrophoresis microchip devices for biochemical assays: Recent developments." Talanta 85, no. 1 (July 2011): 28–34. http://dx.doi.org/10.1016/j.talanta.2011.04.069.

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14

Tsai, Yuan-Chien, Hsiu-Ping Jen, Kuan-Wen Lin, and You-Zung Hsieh. "Fabrication of microfluidic devices using dry film photoresist for microchip capillary electrophoresis." Journal of Chromatography A 1111, no. 2 (April 2006): 267–71. http://dx.doi.org/10.1016/j.chroma.2005.12.003.

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15

Aboud, Nacéra, Davide Ferraro, Myriam Taverna, Stéphanie Descroix, Claire Smadja, and N. Thuy Tran. "Dyneon THV, a fluorinated thermoplastic as a novel material for microchip capillary electrophoresis." Analyst 141, no. 20 (2016): 5776–83. http://dx.doi.org/10.1039/c6an00821f.

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16

Petkovic, Karolina, Anthony Swallow, Robert Stewart, Yuan Gao, Sheng Li, Fiona Glenn, Januar Gotama, et al. "An Integrated Portable Multiplex Microchip Device for Fingerprinting Chemical Warfare Agents." Micromachines 10, no. 9 (September 16, 2019): 617. http://dx.doi.org/10.3390/mi10090617.

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The rapid and reliable detection of chemical and biological agents in the field is important for many applications such as national security, environmental monitoring, infectious diseases screening, and so on. Current commercially available devices may suffer from low field deployability, specificity, and reproducibility, as well as a high false alarm rate. This paper reports the development of a portable lab-on-a-chip device that could address these issues. The device integrates a polymer multiplexed microchip system, a contactless conductivity detector, a data acquisition and signal processing system, and a graphic/user interface. The samples are pre-treated by an on-chip capillary electrophoresis system. The separated analytes are detected by conductivity-based microsensors. Extensive studies are carried out to achieve satisfactory reproducibility of the microchip system. Chemical warfare agents soman (GD), sarin (GB), O-ethyl S-[2-diisoproylaminoethyl] methylphsophonothioate (VX), and their degradation products have been tested on the device. It was demonstrated that the device can fingerprint the tested chemical warfare agents. In addition, the detection of ricin and metal ions in water samples was demonstrated. Such a device could be used for the rapid and sensitive on-site detection of both chemical and biological agents in the future.

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17

Hupert, Mateusz L., W. Jason Guy, Shawn D. Llopis, Hamed Shadpour, Sudheer Rani, Dimitris E. Nikitopoulos, and Steven A. Soper. "Evaluation of micromilled metal mold masters for the replication of microchip electrophoresis devices." Microfluidics and Nanofluidics 3, no. 1 (June 7, 2006): 1–11. http://dx.doi.org/10.1007/s10404-006-0091-x.

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18

Gabriel, Ellen F. M., Claudimir L. do Lago, Ângelo L. Gobbi, Emanuel Carrilho, and Wendell K. T. Coltro. "Characterization of microchip electrophoresis devices fabricated by direct-printing process with colored toner." ELECTROPHORESIS 34, no. 15 (July 12, 2013): 2169–76. http://dx.doi.org/10.1002/elps.201300024.

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19

Llopis, Shawn D., Wieslaw Stryjewski, and Steven A. Soper. "Near-infrared time-resolved fluorescence lifetime determinations in poly(methylmethacrylate) microchip electrophoresis devices." ELECTROPHORESIS 25, no. 21-22 (November 2004): 3810–19. http://dx.doi.org/10.1002/elps.200406054.

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20

Salimi-Moosavi, Hossein, Yutao Jiang, Lianne Lester, Graham McKinnon, and D. Jed Harrison. "A multireflection cell for enhanced absorbance detection in microchip-based capillary electrophoresis devices." Electrophoresis 21, no. 7 (April 1, 2000): 1291–99. http://dx.doi.org/10.1002/(sici)1522-2683(20000401)21:7<1291::aid-elps1291>3.0.co;2-5.

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21

Wang, Ai-Jun, Jing-Juan Xu, and Hong-Yuan Chen. "Enhanced Microchip Electrophoresis of Neurotransmitters on Glucose Oxidase Modified Poly(dimethylsiloxane) Microfluidic Devices." Electroanalysis 19, no. 6 (March 2007): 674–80. http://dx.doi.org/10.1002/elan.200603797.

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22

Kim, Min-Su, Seung Il Cho, Kook-Nyung Lee, and Yong-Kweon Kim. "Fabrication of microchip electrophoresis devices and effects of channel surface properties on separation efficiency." Sensors and Actuators B: Chemical 107, no. 2 (June 2005): 818–24. http://dx.doi.org/10.1016/j.snb.2004.12.069.

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23

Jacobson, Stephen C., Roland Hergenroder, Lance B. Koutny, R. J. Warmack, and J. Michael Ramsey. "Effects of Injection Schemes and Column Geometry on the Performance of Microchip Electrophoresis Devices." Analytical Chemistry 66, no. 7 (April 1994): 1107–13. http://dx.doi.org/10.1021/ac00079a028.

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24

Fogarty, Barbara A., Kathleen E. Heppert, Theodore J. Cory, Kalonie R. Hulbutta, R. Scott Martin, and Susan M. Lunte. "Rapid fabrication of poly(dimethylsiloxane)-based microchip capillary electrophoresis devices using CO2 laser ablation." Analyst 130, no. 6 (2005): 924. http://dx.doi.org/10.1039/b418299e.

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25

Naruishi, Nahoko, Yoshihide Tanaka, Tetsuji Higashi, and Shin-ichi Wakida. "Highly efficient dynamic modification of plastic microfluidic devices using proteins in microchip capillary electrophoresis." Journal of Chromatography A 1130, no. 2 (October 2006): 169–74. http://dx.doi.org/10.1016/j.chroma.2006.07.005.

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26

Bidulock, Allison C. E., Albert van den Berg, and Jan C. T. Eijkel. "Improving chip-to-chip precision in disposable microchip capillary electrophoresis devices with internal standards." ELECTROPHORESIS 36, no. 6 (February 20, 2015): 875–83. http://dx.doi.org/10.1002/elps.201400399.

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27

Fischer, David J., Matthew K. Hulvey, Anne R. Regel, and Susan M. Lunte. "Amperometric detection in microchip electrophoresis devices: Effect of electrode material and alignment on analytical performance." ELECTROPHORESIS 30, no. 19 (October 2009): 3324–33. http://dx.doi.org/10.1002/elps.200900317.

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28

Yap, Yiing C., Rosanne M. Guijt, Tracey C. Dickson, Anna E. King, and Michael C. Breadmore. "Stainless Steel Pinholes for Fast Fabrication of High-Performance Microchip Electrophoresis Devices by CO2 Laser Ablation." Analytical Chemistry 85, no. 21 (October 15, 2013): 10051–56. http://dx.doi.org/10.1021/ac402631g.

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29

Lacher, Nathan A., Nico F. de Rooij, Elisabeth Verpoorte, and Susan M. Lunte. "Comparison of the performance characteristics of poly(dimethylsiloxane) and Pyrex microchip electrophoresis devices for peptide separations." Journal of Chromatography A 1004, no. 1-2 (July 2003): 225–35. http://dx.doi.org/10.1016/s0021-9673(03)00722-2.

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30

Minucci, Angelo, Giulia Canu, Maria De Bonis, Elisabetta Delibato, and Ettore Capoluongo. "Is capillary electrophoresis on microchip devices able to genotype uridine diphosphate glucuronosyltransferase 1A1 TATA-box polymorphisms?" Journal of Separation Science 37, no. 12 (May 2, 2014): 1521–23. http://dx.doi.org/10.1002/jssc.201400235.

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31

Yu, Ming, Qingsong Wang, James E. Patterson, and Adam T. Woolley. "Multilayer Polymer Microchip Capillary Array Electrophoresis Devices with Integrated On-Chip Labeling for High-Throughput Protein Analysis." Analytical Chemistry 83, no. 9 (May 2011): 3541–47. http://dx.doi.org/10.1021/ac200254c.

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32

Sahore, Vishal, Mukul Sonker, Anna V. Nielsen, Radim Knob, Suresh Kumar, and Adam T. Woolley. "Automated microfluidic devices integrating solid-phase extraction, fluorescent labeling, and microchip electrophoresis for preterm birth biomarker analysis." Analytical and Bioanalytical Chemistry 410, no. 3 (August 10, 2017): 933–41. http://dx.doi.org/10.1007/s00216-017-0548-7.

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33

Tähkä, Sari M., Ashkan Bonabi, Maria-Elisa Nordberg, Meeri Kanerva, Ville P. Jokinen, and Tiina M. Sikanen. "Thiol-ene microfluidic devices for microchip electrophoresis: Effects of curing conditions and monomer composition on surface properties." Journal of Chromatography A 1426 (December 2015): 233–40. http://dx.doi.org/10.1016/j.chroma.2015.11.072.

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34

Colombo, Raffaella, and Adele Papetti. "Pre-Concentration and Analysis of Mycotoxins in Food Samples by Capillary Electrophoresis." Molecules 25, no. 15 (July 29, 2020): 3441. http://dx.doi.org/10.3390/molecules25153441.

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Mycotoxins are considered one of the most dangerous agricultural and food contaminants. They are toxic and the development of rapid and sensitive analytical methods to detect and quantify them is a very important issue in the context of food safety and animal/human health. The need to detect mycotoxins at trace levels and to simultaneously analyze many different mycotoxin types became mandatory to protect public health. In fact, European Commission regulations specified both their limits in foodstuffs and official sample preparation protocols in addition to analytical methods to verify their presence. Capillary Electrophoresis (CE) includes different separation modes, allowing many versatile applications in food analysis and safety. In the context of mycotoxins, recent advances to improve CE sensitivity, particularly pre-concentration techniques or miniaturized systems, deserve remarkable attention, as they provide an interesting approach in the analysis of such contaminants in complex food matrices. This review summarizes the applications of CE combined with different pre-concentration approaches, which have been proposed in the literature (mainly) in the last ten years. A section is also dedicated to recent microchip–CE devices since they represent the most promising CE mode for this application.

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35

Sonker, Mukul, Radim Knob, Vishal Sahore, and Adam T. Woolley. "Integrated electrokinetically driven microfluidic devices with pH-mediated solid-phase extraction coupled to microchip electrophoresis for preterm birth biomarkers." ELECTROPHORESIS 38, no. 13-14 (April 25, 2017): 1743–54. http://dx.doi.org/10.1002/elps.201700054.

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36

Caruso, Giuseppe, Nicolò Musso, Margherita Grasso, Angelita Costantino, Giuseppe Lazzarino, Fabio Tascedda, Massimo Gulisano, Susan M. Lunte, and Filippo Caraci. "Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis." Micromachines 11, no. 6 (June 15, 2020): 593. http://dx.doi.org/10.3390/mi11060593.

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The last decades of biological, toxicological, and pharmacological research have deeply changed the way researchers select the most appropriate ‘pre-clinical model’. The absence of relevant animal models for many human diseases, as well as the inaccurate prognosis coming from ‘conventional’ pre-clinical models, are among the major reasons of the failures observed in clinical trials. This evidence has pushed several research groups to move more often from a classic cellular or animal modeling approach to an alternative and broader vision that includes the involvement of microfluidic-based technologies. The use of microfluidic devices offers several benefits including fast analysis times, high sensitivity and reproducibility, the ability to quantitate multiple chemical species, and the simulation of cellular response mimicking the closest human in vivo milieu. Therefore, they represent a useful way to study drug–organ interactions and related safety and toxicity, and to model organ development and various pathologies ‘in a dish’. The present review will address the applicability of microfluidic-based technologies in different systems (2D and 3D). We will focus our attention on applications of microchip electrophoresis (ME) to biological and toxicological studies as well as in drug discovery and development processes. These include high-throughput single-cell gene expression profiling, simultaneous determination of antioxidants and reactive oxygen and nitrogen species, DNA analysis, and sensitive determination of neurotransmitters in biological fluids. We will discuss new data obtained by ME coupled to laser-induced fluorescence (ME-LIF) and electrochemical detection (ME-EC) regarding the production and degradation of nitric oxide, a fundamental signaling molecule regulating virtually every critical cellular function. Finally, the integration of microfluidics with recent innovative technologies—such as organoids, organ-on-chip, and 3D printing—for the design of new in vitro experimental devices will be presented with a specific attention to drug development applications. This ‘composite’ review highlights the potential impact of 2D and 3D microfluidic systems as a fast, inexpensive, and highly sensitive tool for high-throughput drug screening and preclinical toxicological studies.

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37

Yang, Mingpeng, Zhe Huang, and Hui You. "A plug-in electrophoresis microchip with PCB electrodes for contactless conductivity detection." Royal Society Open Science 5, no. 5 (May 2018): 171687. http://dx.doi.org/10.1098/rsos.171687.

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A plug-in electrophoresis microchip for large-scale use aimed at improving maintainability with low fabrication and maintenance costs is proposed in this paper. The plug-in microchip improves the maintainability of a device because the damaged microchannel layer can be changed without needing to cut off the circuit wires in the detection component. Obviously, the plug-in structure reduces waste compared with earlier microchips; at present the whole microchip has to be discarded, including the electrode layer and the microchannel layer. The fabrication cost was reduced as far as possible by adopting a steel template and printed circuit board electrodes that avoided the complex photolithography, metal deposition and sputtering processes. The detection performance of our microchip was assessed by electrophoresis experiments. The results showed an acceptable gradient and stable detection performance. The effect of the installation shift between the microchannel layer and the electrode layer brought about by the plug-in structure was also evaluated. The results indicated that, as long as the shift was controlled within a reasonable scope, its effect on the detection performance was acceptable. The plug-in microchip described in this paper represents a new train of thought for the large-scale use and design of portable instruments with electrophoresis microchips in the future.

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38

Tähkä, Sari M., Ashkan Bonabi, Ville P. Jokinen, and Tiina M. Sikanen. "Aqueous and non-aqueous microchip electrophoresis with on-chip electrospray ionization mass spectrometry on replica-molded thiol-ene microfluidic devices." Journal of Chromatography A 1496 (May 2017): 150–56. http://dx.doi.org/10.1016/j.chroma.2017.03.018.

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An, Ran, Yuncheng Man, Shamreen Iram, Erdem Kucukal, Muhammad Noman Hasan, Ambar Solis-Fuentes, Allison Bode, et al. "Computer Vision and Deep Learning Assisted Microchip Electrophoresis for Integrated Anemia and Sickle Cell Disease Screening." Blood 136, Supplement 1 (November 5, 2020): 46–47. http://dx.doi.org/10.1182/blood-2020-142548.

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Introduction: Anemia affects a third of the world's population with the heaviest burden borne by women and children. Anemia leads to preventable impaired development in children, as well as high morbidity and early mortality among sufferers. Inherited hemoglobin (Hb) disorders, such as sickle cell disease (SCD), are associated with chronic hemolytic anemia causing high morbidity and mortality. Anemia and SCD are inherently associated and are both prevalent in the same regions of the world including sub-Saharan Africa, India, and south-east Asia. Anemia and SCD-related complications can be mitigated by screening, early diagnosis followed by timely intervention. Anemia treatment depends on the accurate characterization of the cause, such as inherited Hb disorders. Meanwhile, Hb disorders or SCD treatments, such as hydroxyurea therapy, requires close monitoring of blood Hb level and the patient's anemia status over time. As a result, it is crucially important to perform integrated detection and monitoring of blood Hb level, anemia status, and Hb variants, especially in areas where anemia and inherited Hb disorders are the most prevalent. Blood Hb level (in g/dL) is used as the main indicator of anemia, while the presence of Hb variants (e.g., sickle Hb or HbS) in blood is the primary indicator of an inherited disorder. The current clinical standards for anemia testing and Hb variant identification are complete blood count (CBC) and High-Performance Liquid Chromatography (HPLC), respectively. State-of-the-art laboratory infrastructure and trained personnel are required for these laboratory tests. However, these resources are typically scarce in low- and middle-income countries, where anemia and Hb disorders are the most prevalent. As a result, there is a dire need for high accuracy portable point-of-care (POC) devices to perform integrated anemia and Hb variant tests with affordable cost and high throughput. Methods: In 2019, the World Health Organization (WHO) listed Hb electrophoresis as an essential in vitro diagnostic (IVD) technology for diagnosing SCD and sickle cell trait. We have leveraged the common Hb electrophoresis method and developed a POC microchip electrophoresis test, Hemoglobin Variant/Anemia (HbVA). This technology is being commercialized under the product name "Gazelle" by Hemex Health Inc. for Hb variant identification with integrated anemia detection (Fig. 1A&B). We hypothesized that computer vision and deep learning will enhance the accuracy and reproducibility of blood Hb level prediction and anemia detection in cellulose acetate based Hb electrophoresis, which is a clinical standard test for Hb variant screening and diagnosis worldwide (Fig. 1C). To test this hypothesis, we integrated, for the first time, a new, computer vision and artificial neural network (ANN) based deep learning imaging and data analysis algorithm, to Hb electrophoresis. Here, we show the feasibility of this new, computer vision and deep learning enabled diagnostic approach via testing of 46 subjects, including individuals with anemia and homozygous (HbSS) or heterozygous (HbSC or Sβ-thalassemia) SCD. Results and Discussion: HbVA computer vision tracked the electrophoresis process real-time and the deep learning neural network algorithm determined Hb levels which demonstrated significant correlation with a Pearson Correlation Coefficient of 0.95 compared to the results of reference standard CBC (Fig.1D). Furthermore, HbVA demonstrated high reproducibly with a mean absolute error of 0.55 g/dL and a bias of -0.10 g/dL (95% limits of agreement: 1.5 g/dL) according to Bland-Altman analysis (Fig. 1E). Anemia determination was achieved with 100% sensitivity and 92.3% specificity with a receiver operating characteristic area under the curve (AUC) of 0.99 (Fig. 1F). Within the same test, subjects with SCD were identified with 100% sensitivity and specificity (Fig. 1G). Overall, the results suggested that computer vision and deep learning methods can be used to extract new information from Hb electrophoresis, enabling, for the first time, reproducible, accurate, and integrated blood Hb level prediction, anemia detection, and Hb variant identification in a single affordable test at the POC. Disclosures An: Hemex Health, Inc.: Patents & Royalties. Hasan:Hemex Health, Inc.: Patents & Royalties. Ahuja:Genentech: Consultancy; Sanofi-Genzyme: Consultancy; XaTec Inc.: Consultancy; XaTec Inc.: Research Funding; XaTec Inc.: Divested equity in a private or publicly-traded company in the past 24 months; Genentech: Honoraria; Sanofi-Genzyme: Honoraria. Little:GBT: Research Funding; Bluebird Bio: Research Funding; BioChip Labs: Patents & Royalties: SCD Biochip (patent, no royalties); Hemex Health, Inc.: Patents & Royalties: Microfluidic electropheresis (patent, no royalties); NHLBI: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees. Gurkan:Hemex Health, Inc.: Consultancy, Current Employment, Patents & Royalties, Research Funding; BioChip Labs: Patents & Royalties; Xatek Inc.: Patents & Royalties; Dx Now Inc.: Patents & Royalties.

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Mecker, Laura C., and R. Scott Martin. "Coupling Microdialysis Sampling to Microchip Electrophoresis in a Reversibly Sealed Device." JALA: Journal of the Association for Laboratory Automation 12, no. 5 (October 2007): 296–302. http://dx.doi.org/10.1016/j.jala.2007.04.008.

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In this article, we describe the fabrication and characterization of a reversibly sealed microchip device that is used to couple microdialysis sampling to microchip electrophoresis. The ability to interface microdialysis sampling and microchip electrophoresis in a device that is amenable to reversible sealing is advantageous from a repeated use standpoint. Commercially, available tubing coming from the microdialysis probe is directly inserted into the chip and flow from the probe is interfaced to the electrophoresis portion of the device through integrated pneumatic valves. Fluorescence detection was used to characterize the poly(dimethylsiloxane)-based device in terms of injection reproducibility. It was found that the entire system (microdialysis probe and microchip device) has a concentration response lag time of 170 s. Microdialysis sampling followed by an electrophoretic separation of amino acids derivatized with naphthalene-2,3-dicarboxaldehyde/cyanide was also demonstrated.

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Sonker, Mukul, Radim Knob, Vishal Sahore, and Adam T. Woolley. "Back Cover: Integrated electrokinetically driven microfluidic devices with pH-mediated solid-phase extraction coupled to microchip electrophoresis for preterm birth biomarkers." ELECTROPHORESIS 38, no. 13-14 (July 2017): NA. http://dx.doi.org/10.1002/elps.201770105.

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Fraiwan, Arwa, Muhammad Noman Hasan, Ran An, Julia Z. Xu, Amy J. Rezac, Nicholas J. Kocmich, Tolulope Oginni, et al. "International Multi-Site Clinical Validation of Point-of-Care Microchip Electrophoresis Test for Hemoglobin Variant Identification." Blood 134, Supplement_1 (November 13, 2019): 3373. http://dx.doi.org/10.1182/blood-2019-129336.

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Introduction: Nearly 24% of the world's population carry hemoglobin (Hb) gene variants, with the large majority of affected births occurring in low-income countries. The most prevalent structural Hb variants are the recessive β-globin gene mutations, βS or S, βC or C, and βE or E1. Hb S mutation is prevalent in sub-Saharan Africa and in Central India. Hb C is common in West Africa, and Hb E is common in Southeast Asia and in India. Homozygotes or compound heterozygotes with βS (e.g., Hb SS or SC) have sickle cell disease (SCD), a chronic sickling disorder associated with pain, chronic multi-organ damage, and high mortality. While Hb EE causes only a mild microcytic anemia, Hb E in combination with β-thalassemia can lead to transfusion dependent thalassemia. Though carriers are typically asymptomatic, they may pass the mutations to their offspring. Screening is needed so that these disorders can be diagnosed early and managed in a timely manner2. For example, in low-income countries, due to lack of nationwide screening and comprehensive care programs, up to 80% of babies born with SCD are undiagnosed and less than half of them survive beyond 5 years of age2. The unmet need for affordable, portable, accurate point-of-care tests to facilitate decentralized hemoglobin testing in resource-constrained countries is well-recognized 2,3. Here, we present international multi-site clinical validation results and high diagnostic accuracy of the 'HemeChip' (Fig. 1), an affordable, 10-minute point-of-care microchip electrophoresis test for identifying common Hb variants S, C, and E. Methods: Institutional Review Board approvals were obtained at each study site, and blood samples were collected as part of the standard clinical care. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. 315 children (6 weeks to 5 years of age) were tested in Kano, Nigeria. Study participants were enrolled at three hospitals, Amino Kano Teaching Hospital, Murtala Mohammed Specialist Hospital, and Hasiya Bayero Pediatric Hospital. 124 subjects (7 weeks to 63 years old) were included in the study at Siriraj Thalassemia Center in Bangkok, Thailand. 298 subjects (8 months to 65 years old) were tested at a referral testing facility of ICMR-National Institute of Research in Tribal Health, located at Late Baliram Kashayap Memorial Medical College, Jagdalpur, Chhattisgarh, India. Blood samples were tested with both HemeChip and the standard reference methods, high performance liquid chromatography or cellulose acetate electrophoresis. Reference test results were not available to the HemeChip users. Similarly, HemeChip test results were not available to the users of the standard reference tests. Clinical validation studies presented here were performed with a fully functional, portable HemeChip prototype developed at Case Western Reserve University (Fig. 1A). A commercial product has been developed based on this technology by Hemex Health Inc. under the product name, GazelleTM(Fig. 1B). Results and Discussion: Among the total 768 tests performed with HemeChip in all test sites, 732 were valid tests, as defined by the Standards for Reporting Diagnostic Accuracy (STARD)4. HemeChip correctly identified all subjects with Hb SS, Hb SC, Hb AS, Hb AE, and Hb EE with 100% accuracy (Table 1). Nine subjects with normal Hb (Hb AA) were identified as HbSS in Nigeria. No subjects with disease were identified as normal or trait by HemeChip. Three subjects with compound heterozygous Hb Sβ-thalassemia (2 subjects with Hb Sβ+-thalassemia, 1 subject with Hb Sβ0-thalassemia) were identified as Hb SS. Sensitivity was 100% for all Hb types tested. Specificity was 98.7% for Hb SS versus other Hb types, and 100% for all other Hb types tested. HemeChip displayed an overall diagnostic accuracy of 98.4% in comparison to standard reference methods for the Hb variants tested in all clinical testing sites (Table 1). HemeChip is a versatile point-of-care system that enables affordable, accurate, decentralized hemoglobin testing in resource-limited settings. References: 1. Weatherall DJ, Clegg JB. Bull World Health Organ. 2001;79(8):704-712. 2. Mburu J, Odame I. International Journal of Laboratory Hematology. 2019;41(S1):82-88. 3. Alapan Y, Fraiwan A, Kucukal E, et al. Expert Review of Medical Devices. 2016;13(12):1073-1093. 4. Bossuyt PM, Reitsma JB, Bruns DE, et al. BMJ : British Medical Journal. 2015;351:h5527. Disclosures Fraiwan: Hemex Health, Inc.: Equity Ownership, Patents & Royalties. Hasan:Hemex Health, Inc.: Equity Ownership, Patents & Royalties. An:Hemex Health, Inc.: Patents & Royalties. Thota:Hemex Health, Inc.: Employment. Piccone:Hemex Health, Inc.: Patents & Royalties. Little:Hemex Health, Inc.: Patents & Royalties; GBT: Research Funding. Gurkan:Hemex Health, Inc.: Consultancy, Employment, Equity Ownership, Patents & Royalties, Research Funding.

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Ueda, Masanori, Yuki Endo, Hirohisa Abe, Hiroki Kuyama, Hiroaki Nakanishi, Akihiro Arai, and Yoshinobu Baba. "Field-inversion electrophoresis on a microchip device." ELECTROPHORESIS 22, no. 2 (January 2001): 217–21. http://dx.doi.org/10.1002/1522-2683(200101)22:2<217::aid-elps217>3.0.co;2-o.

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Johnson, Alicia S., Benjamin T. Mehl, and R. Scott Martin. "Integrated hybrid polystyrene–polydimethylsiloxane device for monitoring cellular release with microchip electrophoresis and electrochemical detection." Analytical Methods 7, no. 3 (2015): 884–93. http://dx.doi.org/10.1039/c4ay02569e.

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In this work, a polystyrene (PS)–polydimethylsiloxane (PDMS) hybrid device was developed to enable the integration of cell culture with analysis by microchip electrophoresis and electrochemical detection.

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Wang, Yineng, Xi Cao, Walter Messina, Anna Hogan, Justina Ugwah, Hanan Alatawi, Ed van Zalen, and Eric Moore. "Development of a Mobile Analytical Chemistry Workstation Using a Silicon Electrochromatography Microchip and Capacitively Coupled Contactless Conductivity Detector." Micromachines 12, no. 3 (February 27, 2021): 239. http://dx.doi.org/10.3390/mi12030239.

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Capillary electrochromatography (CEC) is a separation technique that hybridizes liquid chromatography (LC) and capillary electrophoresis (CE). The selectivity offered by LC stationary phase results in rapid separations, high efficiency, high selectivity, minimal analyte and buffer consumption. Chip-based CE and CEC separation techniques are also gaining interest, as the microchip can provide precise on-chip control over the experiment. Capacitively coupled contactless conductivity detection (C4D) offers the contactless electrode configuration, and thus is not in contact with the solutions under investigation. This prevents contamination, so it can be easy to use as well as maintain. This study investigated a chip-based CE/CEC with C4D technique, including silicon-based microfluidic device fabrication processes with packaging, design and optimization. It also examined the compatibility of the silicon-based CEC microchip interfaced with C4D. In this paper, the authors demonstrated a nanofabrication technique for a novel microchip electrochromatography (MEC) device, whose capability is to be used as a mobile analytical equipment. This research investigated using samples of potassium ions, sodium ions and aspirin (acetylsalicylic acid).

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Gabriel, Ellen Flávia Moreira, Wendell Karlos Tomazelli Coltro, and Carlos D. Garcia. "Fast and versatile fabrication of PMMA microchip electrophoretic devices by laser engraving." ELECTROPHORESIS 35, no. 16 (March 10, 2014): 2325–32. http://dx.doi.org/10.1002/elps.201300511.

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Gabriel, Ellen Flávia Moreira, Wendell Karlos Tomazelli Coltro, and Carlos D. Garcia. "Fast and versatile fabrication of PMMA microchip electrophoretic devices by laser engraving." ELECTROPHORESIS 35, no. 16 (August 2014): NA. http://dx.doi.org/10.1002/elps.201470140.

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Lekwichai, A., S. Porntheeraphat, Win Bunjongpru, W. Sripumkhai, J. Supadech, S. Rahong, C. Hruanun, Amporn Poyai, and J. Nukeaw. "A Disposable Polydimethylsiloxane Microdevice for DNA Amplification." Advanced Materials Research 93-94 (January 2010): 105–8. http://dx.doi.org/10.4028/www.scientific.net/amr.93-94.105.

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In this study, we demonstrate the disposable polydimethylsiloxane (PDMS) microchip provided for DNA amplification. The device consists of two main parts. The first part is PDMS/glass stationary chamber, the other part is a temperature-control microdevice on SiO2/Si substrate. This device consists of a thin film Pt-microheater and a Pt-temperature sensor, which were fabricated with CMOS compatible process. The performance of the device in the DNA amplification shows that, with 10 μl of PCR mixture volume, the approximately 700 bp DNA were successfully amplified within 50 minutes by 30 PCR cycles. The amplified products were comparable with those of a conventional method using electrophoresis. The PCR chip is also suitable for mass production.

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Sueyoshi, Kenji. "Recent Progress of On-line Combination of Preconcentration Device with Microchip Electrophoresis." CHROMATOGRAPHY 33, no. 1 (2012): 25–33. http://dx.doi.org/10.15583/jpchrom.2012.003.

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Xia, Ling, and Debashis Dutta. "A Microchip Device for Enhancing Capillary Zone Electrophoresis Using Pressure-Driven Backflow." Analytical Chemistry 84, no. 22 (October 30, 2012): 10058–63. http://dx.doi.org/10.1021/ac302530y.

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