Chapter 5 – FLOW IMMUNOSENSORS

Publisher Summary Immunosensors have become a predominant form of biosensor due primarily to the ready availability of many different well-characterized antibodies. Work on the kinetic exclusion sensor was initiated in the 1990s by engineers dissatisfied with the performance of fluorescent evanescent waveguide biosensors for the analysis of environmental samples. The goal was to develop an immunosensor system less susceptible than fluorescent waveguide sensors to variables that were difficult to control in real-world samples (pH, ionic strength, ion composition). Flow immunosensors combine the selectivity and sensitivity of traditional immunoassays with the rapid response of a sensor. This chapter describes two different flow immunosensors: a displacement immunosensor that utilizes a non-equilibrium displacement reaction and a kinetic exclusion immunosensor that measures the amount of free antibody-binding sites in an equilibrium mixture of antibody and antigen. It begins with an explanation of the principles of operation of immunosensors. It also presents the evolution of this technology from laboratory prototypes to field applications. Commercial versions of the flow immunosensors have been engineered that integrate fluidics, electronics, and computer control into both portable and autonomous instruments. More recently advanced laboratory prototypes of the displacement immunosensor have been fabricated to improve low-end detection, extend the applications to underwater sensing, enhance field ruggedness, and assist in the manufacturing process. Finally, the study presents the advantages and limitations of flow immunosensors.

[1]  H. Saiki,et al.  Evaluation of a compact bench top immunoassay analyzer for automatic and near continuous monitoring of a sample for environmental contaminants. , 2004, Biosensors & bioelectronics.

[2]  M. Brechbiel,et al.  Binding properties of a monoclonal antibody directed toward lead-chelate complexes. , 2000, Bioconjugate chemistry.

[3]  Anne W. Kusterbeck,et al.  On-Site Immunoanalysis of Nitrate and Nitroaromatic Compounds in Groundwater , 2000 .

[4]  R. Siegel,et al.  Molecular evolution of antibody affinity for sensitive detection of botulinum neurotoxin type A. , 2005, Journal of molecular biology.

[5]  Mazyar Zeinali,et al.  Detection of organics using porphyrin embedded nanoporous organosilicas. , 2007, Biosensors & bioelectronics.

[6]  Yolanda Y. Davidson,et al.  Surface modification of poly(methyl methacrylate) used in the fabrication of microanalytical devices. , 2000, Analytical chemistry.

[7]  F. Ligler,et al.  Novel trifunctional carrier molecule for the fluorescent labeling of haptens. , 1991, Analytical biochemistry.

[8]  M. Unger,et al.  The development of a real-time biosensor for the detection of trace levels of trinitrotoluene (TNT) in aquatic environments. , 2007, Biosensors & bioelectronics.

[9]  Peter B Howell,et al.  A microfluidic mixer with grooves placed on the top and bottom of the channel. , 2005, Lab on a chip.

[10]  Anne W. Kusterbeck,et al.  Enhanced biosensor performance for on‐site field analysis of explosives in water using solid‐phase extraction membranes , 2001 .

[11]  Andreas Plückthun,et al.  Directed evolution of an anti-prion protein scFv fragment to an affinity of 1 pM and its structural interpretation. , 2006, Journal of molecular biology.

[12]  F. Švec,et al.  Monolithic porous polymer for on-chip solid-phase extraction and preconcentration prepared by photoinitiated in situ polymerization within a microfluidic device. , 2001, Analytical chemistry.

[13]  Anne W. Kusterbeck,et al.  Biosensor for underwater chemical sensing (Invited Paper) , 2005, SPIE Defense + Commercial Sensing.

[14]  S. Rabbany,et al.  Theory of Heterogeneity in Displacement Reactions , 1997 .

[15]  D. S. Hage,et al.  Peer Reviewed: Chromatographic Immunoassays , 2001 .

[16]  J M Calvert,et al.  Use of thiol-terminal silanes and heterobifunctional crosslinkers for immobilization of antibodies on silica surfaces. , 1989, Analytical biochemistry.

[17]  F. Ligler,et al.  Use of the USDT flow immunosensor for quantitation of benzoylecgonine in urine. , 1996, Biosensors & bioelectronics.

[18]  H. Ensley,et al.  Novel monoclonal antibodies with specificity for chelated uranium(VI): isolation and binding properties. , 2004, Bioconjugate chemistry.

[19]  A. Mulchandani,et al.  Organophosphorus Hydrolase‐Based Assay for Organophosphate Pesticides , 1999, Biotechnology progress.

[20]  T. Glass,et al.  Measurement of the functional affinity constant of a monoclonal antibody for cell surface receptors using kinetic exclusion fluorescence immunoassay. , 2005, Journal of immunological methods.

[21]  Wayne H. Griest,et al.  Trace Analysis of Explosives in Seawater Using Solid-Phase Microextraction and Gas Chromatography/Ion Trap Mass Spectrometry , 1998 .

[22]  N. Strachan,et al.  Application of an automated particle‐based immunosensor for the detection of aflatoxin B1 in foods , 1997 .

[23]  F. Ligler,et al.  Effect of antibody density on the displacement kinetics of a flow immunoassay. , 1994, Journal of immunological methods.

[24]  D. Walt,et al.  A fiber-optic microarray biosensor using aptamers as receptors. , 2000, Analytical biochemistry.

[25]  Leonard A. Smith,et al.  Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  D. Blake,et al.  Production of recombinant ScFv antibodies against methamidophos from a phage-display library of a hyperimmunized mouse. , 2006, Journal of agricultural and food chemistry.

[27]  H. Saiki,et al.  An immunoassay for small analytes with theoretical detection limits. , 2001, Analytical Chemistry.

[28]  F S Ligler,et al.  Trace detection of explosives using a membrane-based displacement immunoassay. , 2000, Journal of immunological methods.

[29]  Qing X. Li,et al.  Monoclonal antibody-based enzyme-linked immunosorbent assay for the insecticide imidacloprid , 2004 .

[30]  R. M. Jones,et al.  Allosteric binding properties of a monoclonal antibody and its Fab fragment. , 2003, Biochemistry.

[31]  T. Nguyen,et al.  Near real-time biosensor-based detection of 2,4-dinitrophenol. , 2003, Biosensors & bioelectronics.

[32]  Frances S. Ligler,et al.  A membrane-based displacement flow immunoassay , 1998 .

[33]  R. M. Jones,et al.  An immunosensor for autonomous in-line detection of heavy metals: validation for hexavalent uranium , 2005 .

[34]  K R Rogers,et al.  Peer reviewed: environmental biosensors: a status report. , 1996, Environmental science & technology.

[35]  R. Darling,et al.  Kinetic exclusion assay technology: characterization of molecular interactions. , 2004, Assay and drug development technologies.

[36]  Upvan Narang,et al.  A displacement flow immunosensor for explosive detection using microcapillaries , 1997 .

[37]  F. Ligler,et al.  Continuous flow displacement immunosensors: a computational study. , 2000, Analytical biochemistry.

[38]  F. Ligler,et al.  Kinetics of antibody binding at solid-liquid interfaces in flow. , 1992, Journal of immunological methods.

[39]  David W. Conrad,et al.  Antibody-based fluorometric assay for detection of the explosives TNT and PETN , 1995, Photonics West.

[40]  R. Schwartz,et al.  Assessment of an automated solid phase competitive fluoroimmunoassay for benzoylecgonine in untreated urine. , 1999, Journal of immunological methods.

[41]  O. Güven,et al.  Use of amidoximated acrylonitrile/N-vinyl 2-pyrrolidone interpenetrating polymer networks for uranyl ion adsorption from aqueous systems , 2001 .

[42]  Reinhard Bredehorst,et al.  Continuous-flow immunosensor for detection of explosives , 1993 .

[43]  Frances S Ligler,et al.  Fabrication of a capillary immunosensor in polymethyl methacrylate. , 2002, Biosensors & bioelectronics.

[44]  F. Ligler,et al.  Binding kinetics of immobilized antibodies in a flow immunosensor , 1995 .

[45]  H. Saiki,et al.  Development and characterization of new monoclonal antibodies specific for coplanar polychlorinated biphenyls , 2004 .

[46]  L. Roskos,et al.  Demonstration of an in vivo generated sub-picomolar affinity fully human monoclonal antibody to interleukin-8. , 2005, Biochemical and biophysical research communications.

[47]  R. Blake,et al.  Automated kinetic exclusion assays to quantify protein binding interactions in homogeneous solution. , 1999, Analytical biochemistry.

[48]  G. A. Plett,et al.  Trace Explosives Signatures from World War II Unexploded Undersea Ordnance , 1998 .

[49]  Paul T. Charlesa,et al.  Microcapillary reversed-displacement immunosensor for trace level detection of TNT in seawater , 2004 .

[50]  Igor L. Medintz,et al.  Self-assembled TNT biosensor based on modular multifunctional surface-tethered components. , 2005, Analytical chemistry.

[51]  David G Myszka,et al.  Characterizing high-affinity antigen/antibody complexes by kinetic- and equilibrium-based methods. , 2004, Analytical biochemistry.

[52]  Ting Xu,et al.  Automated flow fluorescent immunoassay for part per trillion detection of the neonicotinoid insecticide thiamethoxam. , 2006, Analytica chimica acta.

[53]  K R Rogers,et al.  Detection of 2,4-dichlorophenoxyacetic acid using a fluorescence immunoanalyzer. , 1997, The Analyst.

[54]  James B Delehanty,et al.  Facile generation of heat-stable antiviral and antitoxin single domain antibodies from a semisynthetic llama library. , 2006, Analytical chemistry.

[55]  F. Ligler,et al.  A continuous flow immunoassay for rapid and sensitive detection of small molecules. , 1990, Journal of immunological methods.

[56]  A. Karu,et al.  Haptens and monoclonal antibodies for immunoassay of imidazolinone herbicides. , 2002, Journal of agricultural and food chemistry.

[57]  W. A. Kaptein,et al.  Analysis of cortisol with a flow displacement immunoassay , 1997 .

[58]  A. Kusterbeck,et al.  Application of a Portable Immunosensor To Detect the Explosives TNT and RDX in Groundwater Samples , 1997 .

[59]  A. Kusterbeck,et al.  Synthesis of a fluorescent analog of polychlorinated biphenyls for use in a continuous flow immunosensor assay. , 1995, Bioconjugate chemistry.

[60]  Damià Barceló,et al.  Strengths and limitations of immunoassays for effective and efficient use for pesticide analysis in water samples: A review , 1998 .

[61]  F. Ligler,et al.  Advances in Flow Displacement Immunoassay Design , 1999 .

[62]  Robert M. Carter,et al.  A Fluorescent Biosensor for Detection of Zearalenone , 2000 .

[63]  N. Nath,et al.  A sensitive solid-phase fluoroimmunoassay for detection of opiates in urine , 2000, Applied Biochemistry and Biotechnology.

[64]  Kim R. Rogers,et al.  Biosensors for environmental applications , 1995 .

[65]  R. M. Jones,et al.  Antibody-based sensors for heavy metal ions. , 2001, Biosensors & bioelectronics.

[66]  U. Narang,et al.  Multianalyte detection using a capillary-based flow immunosensor. , 1998, Analytical biochemistry.

[67]  D. Wylie,et al.  Metal Binding Properties of a Monoclonal Antibody Directed toward Metal-Chelate Complexes* , 1996, The Journal of Biological Chemistry.

[68]  A. Kusterbeck,et al.  Environmental immunoassay for the explosive RDX using a fluorescent dye-labeled antigen and the continuous-flow immunosensor , 1997 .

[69]  F. Ligler,et al.  Detection of Cocaine Using the Flow Immunosensor , 1992 .

[70]  P Atanasov,et al.  Immunosensors: electrochemical sensing and other engineering approaches. , 1998, Biosensors & bioelectronics.

[71]  A. Kusterbeck,et al.  Trace level detection of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by microimmunosensor. , 1999, Biosensors & bioelectronics.

[72]  B. Karger,et al.  Noncompetitive immunoassay of small analytes at the femtomolar level by affinity probe capillary electrophoresis: direct analysis of digoxin using a uniform-labeled scFv immunoreagent. , 2000, Analytical chemistry.

[73]  Diana S. Aga,et al.  Immunochemical Technology for Environmental Applications , 1997 .

[74]  R. Giese,et al.  Repetitive hit-and-run fluoroimmunoassay for T-2 toxin. , 1987, Analytical biochemistry.