Polymer Based Biosensors for Pathogen Diagnostics

Over the past three decades researchers have witnessed an enormous amount of activity in the area of biosensors. The major processes involved in any biosensor system are analyte recognition, signal transduction, and readout. Due to their specificity, speed, portability, and low cost, biosensors offer exciting opportunities for numerous decentralized clinical applications – point of care systems. The ongoing trend in biomedicine is to go smaller. For almost a decade, the buzz word has been nano, and the analytical micro devices are now appearing in the clinic. The progress within microfluidic technologies has enabled miniaturization of biomedical systems and biosensors. The down-scaling has several advantages: refined control of fluidics, low sample consumption, applicability to point of care, and low cost. Point of care is an emerging field within medical diagnostics and disease monitoring, and eventually disease control. Employing specially designed micro systems, a patient can be monitored continuously at bed side, and save precious time on commuting between home, doctor and hospital. The technological advancements in the biosensor technology within recent years have accelerated the R&D in point of care devices. Cost benefit is always an important factor in development of novel medical devices. To reduce the expenses of biosensors, the use and cleanroom processing of noble metals should be kept at a minimum. Therefore, we predict a shift in the usage of gold and platinum to degradable polymer materials. This chapter will look further into the advantages and applications of all-polymer microfluidic devices for biomedical diagnostics and compare with traditional systems. In many biosensor applications, only one analyte is of interest, and preferentially it should be isolated from an inhomogeneous patient sample. Section 2 provides the reader with an overview of the different novel microfluidic separation techniques in polymeric devices. Conductive polymers are the focus of section 3. They have many excellent properties and in fact, they can compete with gold in many applications. The focus of section 4 is sensitivity and specificity of biosensors. High sensitivity and specificity is crucial and can be achieved by functionalization with different molecules. The section will primarily center around the use of aptamers which is favourable above antibodies. Different detection methods are applied in biosensors, some of the promising techniques will be summarized in section 5. Finally, section 6 gives an overview of the current status in biosensor development while focusing on ongoing research.

[1]  N. Lee,et al.  Organic electrochemical transistor based immunosensor for prostate specific antigen (PSA) detection using gold nanoparticles for signal amplification. , 2010, Biosensors & bioelectronics.

[2]  A. Bhagat,et al.  Continuous particle separation in spiral microchannels using Dean flows and differential migration. , 2008, Lab on a chip.

[3]  S. Cosnier,et al.  Electrochemical detection of Arachis hypogaea (peanut) agglutinin binding to monovalent and clustered lactosyl motifs immobilized on a polypyrrole film. , 2005, Chemical communications.

[4]  Mehmet Toner,et al.  Blood-on-a-chip. , 2005, Annual review of biomedical engineering.

[5]  Kuang Yu Chen,et al.  Hypusine Is Required for a Sequence-specific Interaction of Eukaryotic Initiation Factor 5A with Postsystematic Evolution of Ligands by Exponential Enrichment RNA* , 2001, The Journal of Biological Chemistry.

[6]  A. Heeger,et al.  Synthesis of electrically conducting organic polymers: halogen derivatives of polyacetylene, (CH)x , 1977 .

[7]  Joseph Jagur-Grodzinski,et al.  Electronically conductive polymers , 2002 .

[8]  Jeong-O Lee,et al.  Aptamers as molecular recognition elements for electrical nanobiosensors , 2007, Analytical and bioanalytical chemistry.

[9]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[10]  Anna De Girolamo Del Mauro,et al.  Ink-jet printing technique in polymer/carbon black sensing device fabrication , 2009 .

[11]  Calum J. McNeil,et al.  Micro-devices for rapid continuous separation of suspensions for use in micro-total-analysis-systems (&mgr;TAS) , 2007, SPIE MOEMS-MEMS.

[12]  H. Amini,et al.  Label-free cell separation and sorting in microfluidic systems , 2010, Analytical and bioanalytical chemistry.

[13]  Jeong-O Lee,et al.  Single-walled carbon nanotube biosensors using aptamers as molecular recognition elements. , 2005, Journal of the American Chemical Society.

[14]  Olivier Lazcka,et al.  Pathogen detection: a perspective of traditional methods and biosensors. , 2007, Biosensors & bioelectronics.

[15]  S. Senthil Kumar,et al.  Simultaneous determination of dopamine and ascorbic acid on poly (3,4-ethylenedioxythiophene) modified glassy carbon electrode , 2006 .

[16]  C. Song,et al.  Fine patterning of glycerol-doped PEDOT:PSS on hydrophobic PVP dielectric with ink jet for source and drain electrode of OTFTs , 2010 .

[17]  Gordon G. Wallace,et al.  Incorporation of Erythrocytes into Polypyrrole to Form the Basis of a Biosensor to Screen for Rhesus (D) Blood Groups and Rhesus (D) Antibodies , 1999 .

[18]  Pranab Goswami,et al.  Recent advances in material science for developing enzyme electrodes. , 2009, Biosensors & bioelectronics.

[19]  A. Daugaard,et al.  Conductive Polymer Functionalization by Click Chemistry , 2008 .

[20]  Keld West,et al.  Direct Fast Patterning of Conductive Polymers Using Agarose Stamping , 2007 .

[21]  J. Giddings,et al.  Field-flow fractionation: analysis of macromolecular, colloidal, and particulate materials. , 1993, Science.

[22]  Nazma N. Inamdar,et al.  Preparation, Properties, and Applications , 2013 .

[23]  A. Pardi,et al.  Molecular interactions and metal binding in the theophylline-binding core of an RNA aptamer. , 2000, RNA.

[24]  Kevin W Plaxco,et al.  A reagentless signal-on architecture for electronic, aptamer-based sensors via target-induced strand displacement. , 2005, Journal of the American Chemical Society.

[25]  A. Bhagat,et al.  Inertial microfluidics for continuous particle separation in spiral microchannels. , 2009, Lab on a chip.

[26]  L. Fonseca,et al.  Applications of polymers for biomolecule immobilization in electrochemical biosensors , 2008 .

[27]  Thomas Laurell,et al.  Continuous separation of cells and particles in microfluidic systems. , 2010, Chemical Society reviews.

[28]  Yongkeun Son,et al.  Glucose biosensor constructed from capped conducting microtubules of PEDOT , 2008 .

[29]  M. Pirrung How to make a DNA chip. , 2002, Angewandte Chemie.

[30]  Miltiades I. Karayannis,et al.  Enzyme Based Amperometric Biosensors for Food Analysis , 2002 .

[31]  Michael C. Petty,et al.  Inkjet-printed polypyrrole thin films for vapour sensing , 2006 .

[32]  R. Tompkins,et al.  Continuous inertial focusing, ordering, and separation of particles in microchannels , 2007, Proceedings of the National Academy of Sciences.

[33]  H. Xie,et al.  Electric-field-assisted growth of functionalized poly(3,4-ethylenedioxythiophene) nanowires for label-free protein detection. , 2009, Small.

[34]  M. Biswas,et al.  Thermal, stability, morphological, and conductivity characteristics of polypyrrole prepared in aqueous medium , 1994 .

[35]  M. G. Finn,et al.  Click Chemistry: Diverse Chemical Function from a Few Good Reactions. , 2001, Angewandte Chemie.

[36]  S. Soper,et al.  Surface immobilization methods for aptamer diagnostic applications , 2008, Analytical and bioanalytical chemistry.

[37]  A. Heeger,et al.  Comparison of the signaling and stability of electrochemical DNA sensors fabricated from 6- or 11-carbon self-assembled monolayers. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[38]  Muhammad Ali Syed,et al.  Advances in aptamers. , 2010, Oligonucleotides.

[39]  Noemi Rozlosnik,et al.  New directions in medical biosensors employing poly(3,4-ethylenedioxy thiophene) derivative-based electrodes , 2009, Analytical and bioanalytical chemistry.

[40]  Kun Han,et al.  Design Strategies for Aptamer-Based Biosensors , 2010, Italian National Conference on Sensors.

[41]  P. Atanassov,et al.  Anion-Exchange Membrane Fuel Cells: Dual-Site Mechanism of Oxygen Reduction Reaction in Alkaline Media on Cobalt−Polypyrrole Electrocatalysts , 2010 .

[42]  Shen-Ming Chen,et al.  Poly(3,4-ethylenedioxythiophene-co-(5-amino-2-naphthalenesulfonic acid)) (PEDOT-PANS) film modified glassy carbon electrode for selective detection of dopamine in the presence of ascorbic acid and uric acid. , 2007, Analytica chimica acta.

[43]  Yuliang Yang,et al.  Preparation, properties and applications of polypyrroles , 2001 .

[44]  Meng H. Lean,et al.  Membrane-free microfiltration by asymmetric inertial migration , 2007 .

[45]  Larry A. Sklar,et al.  The emergence of flow cytometry for sensitive, real-time measurements of molecular interactions , 1998, Nature Biotechnology.

[46]  T. Laurell,et al.  Free flow acoustophoresis: microfluidic-based mode of particle and cell separation. , 2007, Analytical chemistry.

[47]  A. L. Stevens,et al.  Million-fold preconcentration of proteins and peptides by nanofluidic filter. , 2005, Analytical chemistry.

[48]  B. Wessling From conductive polymers to organic metals , 2001 .

[49]  Hansen Bow,et al.  Microfluidics for cell separation , 2010, Medical & Biological Engineering & Computing.

[50]  Emril Mohamed Ali,et al.  Conductivity Shift of Polyethylenedioxythiophenes in Aqueous Solutions from Side-Chain Charge Perturbation , 2007 .

[51]  J. Roncali,et al.  Modification of the electrochemical and electronic properties of electrogenerated poly(3,4-ethylenedioxythiophene) by hydroxymethyl and oligo(oxyethylene) substituents , 2000 .

[52]  B. Liedberg,et al.  In situ spectroscopic investigations of electrochromism and ion transport in a poly (3,4-ethylenedioxythiophene) electrode in a solid state electrochemical cell , 1994 .

[53]  A. Heeger,et al.  An electronic, aptamer-based small-molecule sensor for the rapid, label-free detection of cocaine in adulterated samples and biological fluids. , 2006, Journal of the American Chemical Society.

[54]  Shen-Ming Chen,et al.  Electrocatalysis and simultaneous detection of dopamine and ascorbic acid using poly(3,4-ethylenedioxy)thiophene film modified electrodes , 2006 .