Picomolar or beyond Limit of Detection Using Molecularly Imprinted Polymer-Based Electrochemical Sensors: A Review

Abstract

Over the last decades, molecularly imprinted polymers (MIPs) have emerged as selective synthetic receptors that have a selective binding site for specific analytes/target molecules. MIPs are synthetic analogues to the natural biological antigen-antibody system. Owing to the advantages they exhibit, such as high stability, simple synthetic procedure, and cost-effectiveness, MIPs have been widely used as receptors/sensors for the detection and monitoring of a variety of analytes. Moreover, integrating electrochemical sensors with MIPs offers a promising approach and demonstrates greater potential over traditional MIPs. In this review, we have compiled the methods and techniques for the production of MIP-based electrochemical sensors along with the applications of reported MIP sensors for a variety of analytes. A comprehensive in-depth analysis of recent trends reported on picomolar (pM/10^-12 M)) and beyond picomolar concentration LOD (≥pM) achieved using MIPs sensors is reported. Finally, we discuss the challenges faced and put forward future perspectives along with our conclusion.

Keywords: electrochemical sensors; limit of detection; molecular imprinted polymer; ultrasensitive.

Figure 1

Scheme depicting the stages of preparation of MIPs.

Figure 2

Summary of target analytes discussed in the review.

Figure 3

The process for the preparation of the MIP/GO composite. (1) Drop-casting graphene-oxide sheets on the GCE surface; (2) Electropolymerization of the MIP layer on the surface of GO modified electrode; (3) Template removal and recognition of the target testosterone in different concentrations ([47]).

Figure 4

(A1) 3-D structure of HSA (http://www.rcsb.org/pdb/explore/explore.do?pdbId=1E7H (accessed on 11 October 2022), structural formulas of (A2) functional monomers; (A3) the cross-linking monomer. (B) Illustration of the elaboration procedure of the poly(2,3′-bithiophene) inverse opal imprinting with HSA ([50]).

Figure 5

(a) Calibration plot of ncovNP sensor obtained at the low concentration range of ncovNP (2–111 fM) in LB. The inset shows typical DPV curves used to construct the calibration plot; (b) Selectivity test of ncovNP sensor showing its responses against the different proteins (S1, E2 HCV, BSA, CD48 and ncovNP) applied at concentrations (0.04, 0.07, 0.09, and 0.11 pM) in LB. ([54]).

Figure 6

Scanning electron microscopy images of prepared nano-MIP/MWCNTs nanocomposite, cast on GC electrode ([64]).

Figure 7

(a,b) Photographs of flexible and bendable Au electrodes on surface-roughened PEN with (c) dimensions of the electrodes. The size of the working electrode was 13 mm², with a counter electrode of 4 mm external radius at 1 mm distance; (d) Typical 2-D image of the 3-D interferometric profiler analysis for an Au surface on a flexible PEN surface roughened with 12 μm abrasive paper and (e) SEM image of the surface of the gold working electrode (10,000× magnification). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article) ([78]).

Figure 8

(a) Cyclic voltammograms of individual solutions (prepared in 100 mM of phosphate buffer solution, pH 7.2) of phenol, 3-nitrotyrosine and only phosphate buffer, at a scan rate of 20 mV/s, for one cycle; (b) Cyclic voltammograms for the electropolymerization of 0.30 mM phenol in 100 mM of phosphate buffer, pH 7.0, (scan rate 20 mV/s) at gold-modified electrodes with (dashed line) and without (solid line) the template molecule 3-NT for the first cycle and third cycle; (c) EIS curves of thiol-modified electrode NIP (blue line) and MIP (red line) before (circle symbol) and after (square symbol) template removal (inset figure with gold and thiol-modified electrodes), measured in aqueous solution containing 5 mM [Fe(CN)₆]^3−/4− in 100 mM of phosphate buffer at pH 7.0; (d) Nyquist plots obtained for NIP and MIP materials (inset is the equivalent circuit applied) and calibration curves regarding the MIPs response after 3-NT rebinding. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.) ([78]).