title: Using poly(3-aminophenylboronic acid) thin film with binding-induced ion flux blocking for amperometric detection of hemoglobin A1c.
abstract: This study reports a novel enzyme-free, label-free amperometric method for direct detection of hemoglobin A1c (Hb(A1c)), a potent biomarker for diabetes diagnosis and prognosis. The method relies on an electrode modified with poly(3-aminophenylboronic acid) (PAPBA) nanoparticles (20-50 nm) and a sensing scheme named "binding-induced ion flux blocking." The PAPBA nanoparticles were characterized by FT-IR, XPS, TEM, and SEM. Being a polyaniline derivative, PAPBA showed an ion-dependent redox behavior, in which insertion or extraction of ions into or out of PABPA occurred for charge balance during the electron transfer process. The polymer allowed Hb(A1c) selectively bound to its surface via forming the cis-diol linkage between the boronic acid and sugar moieties. Voltammetric analyses showed that Hb(A1c) binding decreased the redox current of PAPBA; however, the binding did not alter the redox potentials and the apparent diffusivities of ions. This suggests that the redox current of PAPBA decreased due to an Hb(A1c) binding-induced ion flux blocking mechanism, which was then verified and characterized through an in situ electrochemical quartz crystal microbalance (EQCM) study. Assay with Hb(A1c) by differential pulse voltammetry (DPV) indicates that the peak current of a PAPBA electrode has a linear dependence on the logarithm of Hb(A1c) concentration ranging from 0.975 to 156 μM. The Hb(A1c) assay also showed high selectivity against ascorbic acid, dopamine, uric acid, glucose and bovine serum albumin. This study has demonstrated a new method for developing an electrochemical Hb(A1c) biosensor and can be extended to other label-free, indicator-free protein biosensors based on a similar redox polymer electrode.
authors.affiliation: Institute of Polymer Science and Engineering, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Jen-Yuan
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Chemical Engineering, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Tse-Chuan
authors.initials: TC
authors.lastname: Chou
authors.affiliation: Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei 10617, Taiwan. Electronic address: chenlinchi@ntu.edu.tw.
authors.forename: Lin-Chi
authors.initials: LC
authors.lastname: Chen
authors.affiliation: Institute of Polymer Science and Engineering, National Taiwan University, Taipei 10617, Taiwan; Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan. Electronic address: kcho@ntu.edu.tw.
authors.forename: Kuo-Chuan
authors.initials: KC
authors.lastname: Ho
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D001897:Boronic Acids / Q000737:chemistry; D003920:Diabetes Mellitus / Q000097:blood*; D006442:Glycated Hemoglobin / Q000737:chemistry / Q000302:isolation & purification*; D006801:Humans; D053758:Nanoparticles; D011108:Polymers / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001897:Boronic Acids; D006442:Glycated Hemoglobin; D011108:Polymers; C517652:hemoglobin A1c protein, human; C028592:3-aminobenzeneboronic acid
keywords: Diabetes; Electrochemical biosensors; Hemoglobin A1c (Hb(A1c)); Ion flux; Poly(3-aminophenylboronic acid)