Biosensors for the Point of Care

Sensing biologically relevant targets such as microorganisms, DNA, RNA, proteins, or small molecules at low concentrations is important for applications in medical diagnostics, food safety, defense, and environmental monitoring. Of particular interest is point-of-care detection, that is, where the information gained from sensing can be put to use in an immediate course of action in a clinical setting or in the field. A goal of our lab is to exploit the benefits of integrated microfluidics and thermostable chemical assays to create innovative microsystems toward portable, rapid, and sensitive diagnostic platforms that can be used at the point of care.

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Polarity-Switching Electrochemical Sensor for Specific Detection of Single-Nucleotide Mismatches
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Single-nucleotide polymorphisms (SNPs)—genetic variations that involve only a single DNA base-pair—can directly affect transcriptional regulations and protein functions. We present a single-step, room-temperature electrochemical sensor that detects single-nucleotide mismatches with a "polarity-switching" response.
K. Hsieh, R. J. White, B. S. Ferguson, K. W. Plaxco, Y. Xiao and H. T. Soh. Polarity-Switching Electrochemical Sensor for Specific Detection of Single-Nucleotide Mismatches. Angewandte Chemie International Edition, Vol. 123, 1-6 (2011)
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Genetic Analysis of H1N1 Influenza Virus from Throat Swab Samples in a Microfluidic System for Point-of-Care Diagnostics
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The ability to obtain sequence-specific genetic information about rare target organisms directly from complex biological samples at the point-of-care would transform many areas of biotechnology. We demonstrate the detection of influenza H1N1 in throat swab samples at loads as low as 10 TCID50, 4 orders of magnitude below the clinical titer for this virus.
B. S. Ferguson, S. F. Buchsbaum, T-T Wu, K. Hsieh, Y. Xiao, R. Sun and H. T. Soh. Genetic Analysis of H1N1 Influenza Virus from Throat Swab Samples in a Microfluidic System for Point-of-Care Diagnostics. Journal of the American Chemical Society, 133, 9129-9135 (2011)
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Detection of Proteins in Serum by Micromagnetic Aptamer PCR (MAP) Technology
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Accurate detection of diagnostic biomarkers in blood is often challenging because of its complex composition comprising thousands of proteins with concentrations ranging over 12 orders of magnitude. The MAP detection system integrates high-gradient magnetic field sample preparation in a microfluidic device with aptamer-based real-time PCR readout, to achieve highly sensitive and quantitative detection of protein targets directly from complex samples.
A. Csordas, A.E. Gerdon, J.D. Adams, J. Qian, S.S. Oh, Y. Xiao, and H.T. Soh. Detection of Proteins in Serum by Micromagnetic Aptamer PCR (MAP) Technology. Angewandte Chemie International Edition, (49) 355-358 (2010)
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An Electrochemical Sensor for Single Nucleotide Polymorphism Detection in Serum Based on a Triple Stem DNA Probe
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We report here an electrochemical approach that offers, for the first time, single-step, room temperature single nucleotide polymorphism (SNP) detection directly in complex samples (such as blood serum) without the need for target modification, postwashing, or the addition of exogenous reagents. The discrimination capabilities of this sensor greatly exceed those of earlier single- and double-stem electrochemical sensors and it supports the rapid (minutes) and reagentless, detection of single nucleotide substitutions.
Y. Xiao, X.H. Lou, T. Uzawa, K.J.I. Plakos, K.W. Plaxco, and H.T. Soh. An Electrochemical Sensor for Single Nucleotide Polymorphism Detection in Serum Based on a Triple Stem DNA Probe. Journal of the American Chemical Society, (131) 15311-15316 (2009)
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Continuous, Real-Time Monitoring of Cocaine in Undiluted Blood Serum via a Microfluidic, Electrochemical Aptamer-Based Sensor
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Real-time measurement of small molecule analytes directly in complex, unprocessed aqueous samples has been a significant challenge, and successful implementation has been achieved for only a limited number of targets. We report here the Microfluidic Electrochemical Aptamer-based Sensor (MECAS) chip wherein we integrate target-specific DNA aptamers that fold, and thus generate an electrochemical signal, in response to the analyte. We demonstrate the continuous, real-time (∼1 min time resolution) detection of the small-molecule drug cocaine at near physiological, low micromolar concentrations directly in undiluted, otherwise unmodified blood serum.
J. Swensen, Y. Xiao, B.S. Ferguson, A. Lubin, R. Lai, A.J. Heeger, K.W. Plaxco, and H.T. Soh. Continuous, Real-Time Monitoring of Cocaine in Undiluted Blood Serum via a Microfluidic, Electrochemical Aptamer-Based Sensor. Journal of the American Chemical Society, (131) 4262-4266 (2009)
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