title: Poly(3,4-ethylenedioxythiophene) Bearing Phosphorylcholine Groups for Metal-Free, Antibody-Free, and Low-Impedance Biosensors Specific for C-Reactive Protein.
abstract: Conducting polymers possessing biorecognition elements are essential for developing electrical biosensors sensitive and specific to clinically relevant biomolecules. We developed a new 3,4-ethylenedioxythiophene (EDOT) derivative bearing a zwitterionic phosphorylcholine group via a facile synthesis through the Michael-type addition thiol-ene "click" reaction for the detection of an acute-phase biomarker human C-reactive protein (CRP). The phosphorylcholine group, a major headgroup in phospholipid, which is the main constituent of plasma membrane, was also expected to resist nonspecific adsorption of other proteins at the electrode/solution interface. The biomimetic EDOT derivative was randomly copolymerized with EDOT, via an electropolymerization technique with a dopant sodium perchlorate, onto a glassy carbon electrode to make the synthesized polymer film both conductive and target-responsive. The conducting copolymer films were characterized by cyclic voltammetry, scanning electron microscopy, attenuated total reflection Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. The specific interaction of CRP with phosphorylcholine in a calcium-containing buffer solution was determined by differential pulse voltammetry, which measures the altered redox reaction between the indicators ferricyanide/ferrocyanide as a result of the binding event. The conducting polymer-based protein sensor achieved a limit of detection of 37 nM with a dynamic range of 10-160 nM, covering the dynamically changing CRP levels in circulation during the acute phase. The results will enable the development of metal-free, antibody-free, and low-impedance electrochemical biosensors for the screening of nonspecific biomarkers of inflammation and infection.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University , 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Goda
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University , 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Toya
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University , 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University , 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyahara
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D002097:C-Reactive Protein / Q000032:analysis* / Q000737:chemistry*; D004563:Electrochemistry / Q000379:methods; D010767:Phosphorylcholine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D011108:Polymers; C121383:poly(3,4-ethylene dioxythiophene); D010767:Phosphorylcholine; D002097:C-Reactive Protein
keywords: conducting polymer; differential pulse voltammetry; electrochemical impedance spectroscopy; phosphorylcholine; thiol−ene reaction