Miniaturized technology for protein and nucleic acid point-of-care testing

The field of point-of-care (POC) testing technology is developing quickly and producing instruments that are increasingly reliable, while their size is being gradually reduced. Proteins are a common target for POC analyses and the detection of protein markers typically involves immunoassays aimed at detecting different groups of proteins such as tumor markers, inflammation proteins, and cardiac markers; but other techniques can also be used to analyze plasma proteins. In the case of nucleic acids, hybridization and amplification strategies can be used to record electromagnetic or electric signals. These techniques allow for the identification of specific viral or bacterial infections as well as specific cancers. In this review, we consider some of the latest advances in the analysis of specific nucleic acid and protein biomarkers, taking into account their trend toward miniaturization and paying special attention to the technology that can be implemented in future applications, such as lab-on-a-chip instruments.

[1]  T. Akamatsu,et al.  Evaluation of urinary rapid test for Helicobacter pylori in general practice , 2001, Journal of clinical laboratory analysis.

[2]  J. Crain,et al.  Fast DNA and protein microarray tests for the diagnosis of hepatitis C virus infection on a single platform , 2011, Analytical and bioanalytical chemistry.

[3]  Eric P. Skaar,et al.  Miniature on-chip detection of unpurified methicillin-resistant Staphylococcus aureus (MRSA) DNA using real-time PCR. , 2010, Journal of biotechnology.

[4]  C. Klapperich,et al.  Design and testing of a disposable microfluidic chemiluminescent immunoassay for disease biomarkers in human serum samples , 2007, Biomedical microdevices.

[5]  W. Qiu,et al.  Integration of cell phone imaging with microchip ELISA to detect ovarian cancer HE4 biomarker in urine at the point-of-care. , 2011, Lab on a chip.

[6]  Q. Xiang,et al.  Miniature real time PCR on chip with multi-channel fiber optical fluorescence detection module , 2007, Biomedical microdevices.

[7]  Geertruida A. Posthuma-Trumpie,et al.  Lateral flow (immuno)assay: its strengths, weaknesses, opportunities and threats. A literature survey , 2009, Analytical and bioanalytical chemistry.

[8]  Peng Liu,et al.  Real-time forensic DNA analysis at a crime scene using a portable microchip analyzer. , 2008, Forensic science international. Genetics.

[9]  Frank F Bier,et al.  Helicase dependent OnChip-amplification and its use in multiplex pathogen detection. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[10]  H. Yoshimura,et al.  Spot test of urinary protein using erythrosin B and a membrane film. , 2010, The Analyst.

[11]  Amy E Herr,et al.  Microfluidic immunoassays as rapid saliva-based clinical diagnostics , 2007, Proceedings of the National Academy of Sciences.

[12]  J. Compton,et al.  Nucleic acid sequence-based amplification , 1991, Nature.

[13]  Thomas Justin Clark,et al.  The Triage Cardiac Panel , 2002 .

[14]  Daniel R. Garalde,et al.  Mapping the position of DNA polymerase-bound DNA templates in a nanopore at 5 A resolution. , 2009, ACS nano.

[15]  Ole Bang,et al.  Towards biochips using microstructured optical fiber sensors , 2006, Analytical and bioanalytical chemistry.

[16]  Hui Chen,et al.  Predicting viruses accurately by a multiplex microfluidic loop-mediated isothermal amplification chip. , 2011, Analytical chemistry.

[17]  Christof M. Niemeyer,et al.  User configurable microfluidic device for multiplexed immunoassays based on DNA-directed assembly. , 2009, Analytical chemistry.

[18]  Ronald F Renzi,et al.  An integrated microfluidic platform for sensitive and rapid detection of biological toxins. , 2008, Lab on a chip.

[19]  Paul Leonard,et al.  Biosensor developments: application to prostate-specific antigen detection. , 2007, Trends in biotechnology.

[20]  Hyuk-Jae Chang,et al.  Development of a point-of-care assay system for high-sensitivity C-reactive protein in whole blood. , 2003, Clinica chimica acta; international journal of clinical chemistry.

[21]  Guodong Liu,et al.  Disposable electrochemical immunosensor diagnosis device based on nanoparticle probe and immunochromatographic strip. , 2007, Analytical chemistry.

[22]  E. Schleicher,et al.  Inflammation markers in point-of-care testing (POCT) , 2009, Analytical and bioanalytical chemistry.

[23]  Mizuo Maeda,et al.  Power-free sequential injection for microchip immunoassay toward point-of-care testing. , 2006, Lab on a chip.

[24]  S. Kasner,et al.  Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke: The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study , 2009, Stroke.

[25]  Michele Palmieri,et al.  Polymerase chain reaction of 2-kb cyanobacterial gene and human anti-alpha1-chymotrypsin gene from genomic DNA on the In-Check single-use microfabricated silicon chip. , 2006, Analytical biochemistry.

[26]  Gildas Morvan,et al.  A literature survey , 2013 .

[27]  Igor L. Medintz,et al.  Rapid determination of monozygous twinning with a microfabricated capillary array electrophoresis genetic-analysis device. , 2008, Clinical chemistry.

[28]  Ren Sun,et al.  Genetic analysis of H1N1 influenza virus from throat swab samples in a microfluidic system for point-of-care diagnostics. , 2011, Journal of the American Chemical Society.

[29]  Axel Scherer,et al.  Internally calibrated quantification of protein analytes in human serum by fluorescence immunoassays in disposable elastomeric microfluidic devices , 2008, Electrophoresis.

[30]  D. Branton,et al.  Microsecond time-scale discrimination among polycytidylic acid, polyadenylic acid, and polyuridylic acid as homopolymers or as segments within single RNA molecules. , 1999, Biophysical journal.

[31]  Richard A Mathies,et al.  Microfabricated bioprocessor for integrated nanoliter-scale Sanger DNA sequencing. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Yasufumi Mizuno,et al.  Hand-held monitor of sympathetic nervous system using salivary amylase activity and its validation by driver fatigue assessment. , 2006, Biosensors & bioelectronics.

[33]  Guodong Liu,et al.  A nanoparticle label/immunochromatographic electrochemical biosensor for rapid and sensitive detection of prostate-specific antigen. , 2008, Biosensors & bioelectronics.

[34]  Niko Hildebrandt,et al.  Toward sensitive, quantitative point-of-care testing (POCT) of protein markers: miniaturization of a homogeneous time-resolved fluoroimmunoassay for prostate-specific antigen detection. , 2011, The Analyst.

[35]  R. Bashir,et al.  Lipid bilayer coated Al2O3 nanopore sensors: towards a hybrid biological solid-state nanopore , 2011, Biomedical microdevices.

[36]  E. Messing,et al.  Detection of bladder cancer using a point-of-care proteomic assay. , 2005, JAMA.

[37]  A. Thomas.  Point of Care Testing – Needs, Opportunity and Innovation , 2011 .

[38]  John T McDevitt,et al.  Application of microchip assay system for the measurement of C-reactive protein in human saliva. , 2005, Lab on a chip.

[39]  Dario Kriz,et al.  Rapid one-step whole blood C–reactive protein magnetic permeability immunoassay with monoclonal antibody conjugated nanoparticles as superparamagnetic labels and enhanced sedimentation , 2006, Analytical and bioanalytical chemistry.

[40]  Fang Wang,et al.  Performance of nanoliter-sized droplet-based microfluidic PCR , 2009, Biomedical microdevices.

[41]  David R Walt,et al.  Fiber-optic microsphere-based antibody array for the analysis of inflammatory cytokines in saliva. , 2009, Analytical chemistry.

[42]  I-Ming Hsing,et al.  A DNA biochip for on-the-spot multiplexed pathogen identification , 2006, Nucleic acids research.

[43]  Gillian Tully,et al.  An automated instrument for human STR identification: Design, characterization, and experimental validation , 2010, Electrophoresis.

[44]  Albrecht Brandenburg,et al.  Compact point-of-care system for clinical diagnostics , 2009 .

[45]  Pei-Jer Chen,et al.  The evolution of real-time PCR machines to real-time PCR chips. , 2010, Biosensors & bioelectronics.

[46]  Ioanis Katakis,et al.  Design and testing of a packaged microfluidic cell for the multiplexed electrochemical detection of cancer markers , 2009, Electrophoresis.

[47]  L. Gervais,et al.  Toward one-step point-of-care immunodiagnostics using capillary-driven microfluidics and PDMS substrates. , 2009, Lab on a chip.

[48]  Daniel R. Garalde,et al.  Distinct Complexes of DNA Polymerase I (Klenow Fragment) for Base and Sugar Discrimination during Nucleotide Substrate Selection* , 2011, The Journal of Biological Chemistry.

[49]  Chih-Ming Ho,et al.  Electrochemical detection of low-copy number salivary RNA based on specific signal amplification with a hairpin probe , 2008, Nucleic acids research.

[50]  D. Metzgar,et al.  Integrated capillary electrophoresis microsystem for multiplex analysis of human respiratory viruses. , 2010, Analytical chemistry.

[51]  Hongchen Gu,et al.  Development of lateral flow immunoassay system based on superparamagnetic nanobeads as labels for rapid quantitative detection of cardiac troponin I , 2009 .

[52]  I. Tothill,et al.  Development of a sensitive detection method of cancer biomarkers in human serum (75%) using a quartz crystal microbalance sensor and nanoparticles amplification system. , 2010, Talanta.

[53]  Melanie Kess,et al.  Multi-parameter determination of TNFα, PCT and CRP for point-of-care testing. , 2011, The Analyst.

[54]  Guodong Liu,et al.  Aptamer-functionalized gold nanoparticles as probes in a dry-reagent strip biosensor for protein analysis. , 2009, Analytical chemistry.

[55]  Ying Xu,et al.  Operon prediction in Pyrococcus furiosus , 2006 .

[56]  John Spertus,et al.  Use of saliva-based nano-biochip tests for acute myocardial infarction at the point of care: a feasibility study. , 2009, Clinical chemistry.

[57]  S. Lehmann,et al.  Protein biochip systems for the clinical laboratory , 2005, Clinical chemistry and laboratory medicine.

[58]  Ulrich Friess,et al.  Cardiac markers: a clear cause for point-of-care testing , 2009, Analytical and bioanalytical chemistry.

[59]  K. Lieberman,et al.  Processive replication of single DNA molecules in a nanopore catalyzed by phi29 DNA polymerase. , 2010, Journal of the American Chemical Society.

[60]  Rebecca Richards-Kortum,et al.  Oligonucleotide-Gold Nanoparticle Networks for Detection of Cryptosporidium parvum Heat Shock Protein 70 mRNA , 2009, Journal of Clinical Microbiology.

[61]  M. P. Sotomayor,et al.  Disposable immunosensor for human cardiac troponin T based on streptavidin-microsphere modified screen-printed electrode. , 2010, Biosensors & bioelectronics.

[62]  L. Hood,et al.  Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood , 2008, Nature Biotechnology.

[63]  Shibing Long,et al.  Enhanced DNA Sequencing Performance Through Edge‐Hydrogenation of Graphene Electrodes , 2010, 1012.0031.

[64]  Gwo-Bin Lee,et al.  An integrated microfluidic loop-mediated-isothermal-amplification system for rapid sample pre-treatment and detection of viruses. , 2011, Biosensors & bioelectronics.

[65]  B. Sullenger,et al.  Aptamers: an emerging class of therapeutics. , 2005, Annual review of medicine.

[66]  Xiaohong Fang,et al.  Aptamers generated from cell-SELEX for molecular medicine: a chemical biology approach. , 2010, Accounts of chemical research.

[67]  Tae Seok Seo,et al.  Sample stacking capillary electrophoretic microdevice for highly sensitive mini Y short tandem repeat genotyping , 2010, Electrophoresis.

[68]  Guodong Liu,et al.  Aptamer-nanoparticle strip biosensor for sensitive detection of cancer cells. , 2009, Analytical chemistry.

[69]  T. J. Clark,et al.  The Triage Cardiac Panel: Cardiac Markers for the Triage System , 2002 .

[70]  R. B. Cary,et al.  Lateral flow microarrays: a novel platform for rapid nucleic acid detection based on miniaturized lateral flow chromatography , 2007, Nucleic acids research.

[71]  L. Alberio,et al.  Monitoring thrombin generation by electrochemistry: development of an amperometric biosensor screening test for plasma and whole blood. , 2009, Clinical chemistry.

[72]  Axel Warsinke,et al.  Point-of-care testing of proteins , 2009, Analytical and bioanalytical chemistry.

[73]  Chan Woo Park,et al.  Direct label-free electrical immunodetection in human serum using a flow-through-apparatus approach with integrated field-effect transistors. , 2010, Biosensors & bioelectronics.

[74]  Tom Palenius,et al.  Ultrarapid, ultrasensitive one-step kinetic immunoassay for C-reactive protein (CRP) in whole blood samples: measurement of the entire CRP concentration range with a single sample dilution. , 2002, Clinical chemistry.

[75]  T. Kouri,et al.  Evaluation of the ARKRAY AUTION Eleven® reflectometer in detecting microalbuminuria with AUTION Screen® test strips and proteinuria with AUTION Sticks 10PA® strips , 2009, Scandinavian journal of clinical and laboratory investigation.

[76]  T. Notomi,et al.  Loop-mediated isothermal amplification of DNA. , 2000, Nucleic acids research.

[77]  Feng Yan,et al.  Electric field-driven strategy for multiplexed detection of protein biomarkers using a disposable reagentless electrochemical immunosensor array. , 2008, Analytical chemistry.

[78]  A. Scherer,et al.  Internally calibrated quantification of VEGF in human plasma by fluorescence immunoassays in disposable elastomeric microfluidic devices. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[79]  Mark Akeson,et al.  Replication of Individual DNA Molecules under Electronic Control Using a Protein Nanopore , 2010, Nature nanotechnology.

[80]  H. Karnes,et al.  Microfluidic capillary system for immunoaffinity separations of C-reactive protein in human serum and cerebrospinal fluid. , 2008, Analytical chemistry.

[81]  J. Szostak,et al.  In vitro selection of functional nucleic acids. , 1999, Annual review of biochemistry.

[82]  Valerie Mioulet,et al.  Development and Initial Results of a Low Cost, Disposable, Point-of-Care Testing Device for Pathogen Detection , 2011, IEEE Transactions on Biomedical Engineering.