Glycated hemoglobin (HbA1c) affinity biosensors with ring-shaped interdigital electrodes on impedance measurement.

Glycated hemoglobin (HbA1c) is one of the most important diagnostic assays for the long-term mark of glycaemic control in diabetes. This study presents an affinity biosensor for HbA1c detection which is label-free based on the impedance measurement, and it features low cost, low sample volume, and requires no additional reagent in experiments. The ring-shaped interdigital electrodes (RSIDEs) are designed to promote the distribution uniformity and immobilization efficiency of HbA1c, and are further employed to characterize the impedance change and identify various concentrations of HbA1c. The self-assembled monolayer (SAM) of thiophene-3-boronic acid (T3BA) is provided to modify the gold electrode surface. Afterwards, the esterification reaction between HbA1c and T3BA produces a relative change of electrical property on the electrode surface. The RSIDEs with SAM of T3BA exhibit a wide range from 100 to 10 ng/µL producing an approximate logarithmic decrease of impedance, a low detection limit of 1 ng/µL, a good selectivity and short-term stability for HbA1c determination. The remarkable advantages (miniaturization and low-cost) fill the bill of point-care diagnostics for portable sensor development.

[1]  R. Kurita,et al.  Miniaturized thin-layer radial flow cell with interdigitated ring-shaped microarray electrode used as amperometric detector for capillary electrophoresis. , 2000, Journal of chromatography. A.

[2]  M. Rewers,et al.  Global Estimates for Prevalence of Diabetes Mellitus and Impaired Glucose Tolerance in Adults , 1993, Diabetes Care.

[3]  Wei Li,et al.  A single-use, disposable iridium-modified electrochemical biosensor for fructosyl valine for the glycoslated hemoglobin detection , 2009 .

[4]  Y. Han,et al.  Electrochemical Assay for Glycated Hemoglobin based on the Magnetic Particle-supported Concentration Coupled to Boronate-diol Interactions , 2010 .

[5]  M. Okochi,et al.  On-chip type cation-exchange chromatography with ferrocene-labeled anti-hemoglobin antibody and electrochemical detector for determination of hemoglobin A1c level. , 2009, Analytica chimica acta.

[6]  Shanhong Xia,et al.  A micro potentiometric immunosensor for hemoglobin-A1c level detection based on mixed SAMs wrapped nano-spheres array. , 2011, Biosensors & bioelectronics.

[7]  Robert Langer,et al.  Long-Term Stability of Self-Assembled Monolayers in Biological Media , 2003 .

[8]  B. Mattiasson,et al.  Separation of mistletoe lectins based on the degree of glycosylation using boronate affinity chromatography. , 2001, Journal of chromatography. A.

[9]  Toby Mottram,et al.  Biosensor Technology addressing Agricultural Problems , 2003 .

[10]  W. Quan,et al.  Enlargement of High Density Lipoprotein in Mice via Liver X Receptor Activation Requires Apolipoprotein E and Is Abolished by Cholesteryl Ester Transfer Protein Expression* , 2003, Journal of Biological Chemistry.

[11]  M. Jenkins,et al.  Capillary Electrophoresis of Hemoglobin , 2003, Clinical chemistry and laboratory medicine.

[12]  James N Turner,et al.  On-chip micro-biosensor for the detection of human CD4(+) cells based on AC impedance and optical analysis. , 2005, Biosensors & bioelectronics.

[13]  Shanhong Xia,et al.  CMOS and MEMS based micro hemoglobin-A1c biosensors fabricated by various antibody immobilization methods , 2011 .

[14]  M. Steffes,et al.  Glycohemoglobin: a primary predictor of the development or reversal of complications of diabetes mellitus. , 2001, Clinical chemistry.

[15]  Byoung-Yong Chang,et al.  Selective electrochemical sensing of glycated hemoglobin (HbA1c) on thiophene-3-boronic acid self-assembled monolayer covered gold electrodes. , 2008, Analytical chemistry.

[16]  Petr Skládal,et al.  Development of a combined setup for simultaneous detection of total and glycated haemoglobin content in blood samples. , 2006, Biosensors & bioelectronics.

[17]  Frieder W. Scheller,et al.  Membrane-immobilized haptoglobin as affinity matrix for a hemoglobin-A1c immunosensor , 2002 .

[18]  Robert J Hamers,et al.  Frequency-dependent electrical detection of protein binding events. , 2004, The Analyst.

[19]  Jan Halámek,et al.  Signal Amplification in Immunoassays Using Labeling via Boronic Acid Binding to the Sugar Moiety of Immunoglobulin G: Proof of Concept for Glycated Hemoglobin , 2007 .

[20]  Ling-Sheng Jang,et al.  Detection of glycated hemoglobin (HbA1c) based on impedance measurement with parallel electrodes integrated into a microfluidic device , 2012 .

[21]  T. Chou,et al.  Integrated microfluidic system for electrochemical sensing of glycosylated hemoglobin , 2009, 2009 IEEE 3rd International Conference on Nano/Molecular Medicine and Engineering.

[22]  Ming-Chih Ho,et al.  A planar interdigitated ring electrode array via dielectrophoresis for uniform patterning of cells. , 2008, Biosensors & bioelectronics.

[23]  A. Sanz-Medel,et al.  Simultaneous determination of glycated haemoglobin, a long term biomarker of diabetes mellitus, and total haemoglobin by isotope dilution and HPLC-ICP-MS , 2008 .

[24]  Shanhong Xia,et al.  A micro-potentiometric hemoglobin immunosensor based on electropolymerized polypyrrole-gold nanoparticles composite. , 2009, Biosensors & bioelectronics.

[25]  P. Gallop,et al.  Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c. , 1975, Biochemical and biophysical research communications.

[26]  H. Yamanaka,et al.  Optimization of incubation time of protein Tc85 in the construction of biosensor: Is the EIS a good tool? , 2010 .

[27]  H Morgan,et al.  Analytical electric field and sensitivity analysis for two microfluidic impedance cytometer designs. , 2007, IET nanobiotechnology.

[28]  Jan Přibyl,et al.  Quartz crystal biosensor for detection of sugars and glycated hemoglobin , 2005 .

[29]  Noël Burais,et al.  Atrazine analysis using an impedimetric immunosensor based on mixed biotinylated self-assembled monolayer , 2006 .

[30]  J. Justin Gooding,et al.  Electrochemical DNA Hybridization Biosensors , 2002 .