Molecularly Imprinted Artificial Biointerface for an Enzyme-Free Glucose Transistor

Abstract

A platform based on a highly selective and sensitive detection device functionalized with a well-designed artificial biointerface is required for versatile biosensors. We develop a molecularly imprinted polymer (MIP)-coated gate field-effect transistor (FET) biosensor for low-concentration glucose detection in biological fluid samples such as tears in an enzyme-free manner. The MIP includes glucose templates (GluMIP), in which glucose binds to vinylphenylboronic acid in the copolymerized membrane, resulting in the change in the density of molecular charges of the phenylboronic acid (PBA)/glucose complex. The FET biosensor can detect small biomolecules as long as biomolecular recognition events cause intrinsic changes in the density of molecular charges. As a result, the changes in the output voltage detected using the GluMIP-based FET sensor are fitted to the Langmuir adsorption isotherm equation at various concentrations of sugars, showing the low detection limit of 3 μM and the high sensitivity of 115 mV/decade from 100 μM to 4 mM glucose. On the basis of the equation, the stability constant (K a) of PBA with glucose is calculated and found to markedly increase to K a = 1192 M–1, which is higher by a factor of a few hundreds than K a = 4.6 M–1 obtained by nonelectrical detection methods. Moreover, the GluMIP-coated gate FET sensor shows an approximately 200-fold higher selectivity for glucose than for fructose. This is because glucose binds to PBA more selectively than fructose in the templates, resulting in the generation of negative charges. The electrical properties of the MIP-coated electrode are also evaluated by measuring capacitance. Our work suggests a new strategy of designing a platform based on the MIP-coated gate FET biosensor, which is suitable for a highly selective, sensitive, enzyme-free biosensing system.

MIPs for commercial application in low-cost sensors and assays – An overview of the current status quo

“…The same group has demonstrated similar results, using the sensor for the detection of human chorionic gonadotropin hormone, illustrating its potential application in home-pregnancy testing, and d-arabitol for fungal infection diagnosis [ 106 , 107 ]. Other groups have used FET-based MIP sensors for the detection of prostate specific antigen in human plasma [ 108 ], glucose in buffer [ 109 ], and gluten in food products [ 110 ].…”

Biologically Coupled Gate Field-Effect Transistors Meet in Vitro Diagnostics

“…73 Among them, vinyl phenylboronic acid (PBA) has been copolymerized as a functional monomer bound to small biomarkers based on diol binding in MIP biointerfaces of FET biosensors. 67−69 A PBA-MIP-coated gate FET sensor was applied to the selective detection of glucose molecules, as shown in Figure 6b. In fact, the stability constant ( K a ) of PBA with glucose was found to markedly increase to K a = 1192 M –1 , which was 2 orders of magnitude higher than K a = 4.6 M –1 obtained by nonelectrical detection methods.…”

Molecularly Imprinted Materials for Selective Biological Recognition

“…Molecular imprinting is an approach in which templates (including ion, molecule, macromolecular assembly, and micro‐organism) and functional monomers co‐assemble through covalent/non‐covalent interactions, polymerize to form polymers, and subsequently remove templates to make spaces for constructing selective recognition sites . Molecularly imprinted polymers (MIPs) are remarkably versatile and biomimetic materials (artificial antibodies) . Inspired by nature, the design, synthesis, characterization, and application of MIPs have been developed continuously, which reflect the maturation of molecular imprinted techniques (MIT) and its wide interest in the scientific community.…”

“…[1][2][3] Molecularly imprinted polymers (MIPs) are remark ably versatile and biomimetic materials (artificial antibodies). [4,5] Inspired by nature, the design, [6,7] synthesis, [8,9] char acterization, [10,11] and application [12,13] of MIPs have been developed continuously, which reflect the maturation of molecular imprinted techniques (MIT) and its wide interest in the scientific community. Sci entists and engineers increasingly use MIPs in biomedical fields, particularly chemo/biosensor, [14,15] drug delivery, [16,17] and biorecognition, [18,19] owing to the exceptional properties of MIPs: excellent mechanical strength and flexibility, [20][21][22][23] biocompatibility, [24,25] biodegradability, [26] and ease of synthesis [27] into a broad variety of multiscale hier archical morphologies.…”