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

Abstract

Molecularly imprinted polymers (MIPs) have emerged over the past few decades as interesting synthetic alternatives due to their long-term chemical and physical stability and low-cost synthesis procedure. They have been integrated into many sensing platforms and assay formats for the detection of various targets, ranging from small molecules to macromolecular entities such as pathogens and whole cells. Despite the advantages MIPs have over natural receptors in terms of commercialization, the striking success stories of biosensor applications such as the glucose meter or the self-test for pregnancy have not been matched by MIP-based sensor or detection kits yet. In this review, we zoom in on the commercial potential of MIP technology and aim to summarize the latest developments in their commercialization and integration into sensors and assays with high commercial potential. We will also analyze which bottlenecks are inflicting with commercialization and how recent advances in commercial MIP synthesis could overcome these obstacles in order for MIPs to truly achieve their commercial potential in the near future.

Keywords: Biosensing; Commercialization; Diagnostics; Lateral flow assays; Molecularly imprinted polymers.

Fig. 1

A generic schematic demonstrating the fundamental principles behind the synthesis and extraction of a MIP.

Fig. 2

Thermocouples were coated with MIP particles by dip-coating a polystyrene layer onto a copper-welded titanium catheter wire (left). Two wires were coated with MIP particles, two with NIP particles and integrated into one catheter (middle), allowing for the impedimetric detection of histamine in intestinal fluid (right). Figure reproduced from [79] with permission. Copyright Elsevier 2020.

Fig. 3

Lactate MIPs were made on top of a patch containing silver nanowires by electropolymerization (top). This patch, containing an integrated PDMS flow cell and a measuring chamber were attached to a test person’s arm, allowing to monitor lactate levels in sweat. Reproduced with permission from [85]. Copyright Elsevier 2020.

Fig. 4

QCM-based detection of 4 different cannabinoids (JWH-018, JWH-073, JWH-018 pentanoic acid and JWH-073 butanoic acid respectively A-D). The data show that it is possible to quantify these compounds in synthetic urine down to concentrations in the pg/mL range. Re-used from [131] with permission. Copyright Elsevier 2018.

Fig. 5

Thermocouples were dip-coated with a poly-lactic acid adhesive layer and roll-coated with MIP particles. These thermocouples were used to detect the presence of various neurotransmitter in buffer. Re-used from [162] with permission on an open-access license agreement, Copyright American Chemical Society 2017.

Fig. 6

Gold SPR chips were coated with MIPs for the quantification of secreted bacterial factor (RoxP). Skin swaps were taken at various positions on the bodies of two female and one male volunteer and the MIP-based SPR sensor was able to detect RoxP on all positions with results being validated using a golden standard ELISA test. Adapted from [184] with permission. Copyright American Chemical Society 2019.

Fig. 7

Fluorescent dual-emission MIP nanoparticles were made by integrating red and blue fluorescent quantum dots into the polymer shell (top). These particles were immobilized onto test strips by soaking them in MIP solution. The result is a pH-indicator-like test strip that allows the end-user to quantify the amount of dopamine in a biological sample. Adapted with permission from [209}, Copyright John Wiley and Sons 2018. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).

Fig. 8

MIP membranes deposited round a cellulose paper, using nanoparticles as a spacer ring between the paper and the MIP layer. The MIP membranes selectively bind BPA, preventing the oxidation of peroxidation, leaving the color of the cellulose paper unchanged. In absence of BPA, the generation of OH-species will discolor the paper. Re-used with permission from [221], Copyright Elsevier 2017.

Fig. 9

MIPs were imprinted with algal metabolites geosmin and 2-methylisoborneol, extracted and loaded with substrates coupled to fluorescent tag. In presence of the target, the fluorescently labeled substrate gets displaced due its lower affinity for the MIP. Illumination of the filtrate with a simple UV-lamp visually confirms the presence or absence of the target. Adapted with permission from [224]. Copyright Elsevier 2019.

Fig. 10

Triazophos MIPs can be used instead of antibodies in a lateral flow assay. MIPs were used as capture antibody in the sorbent test line path of the assay. Samples were mixed with FITC-labeled target molecules. Presence of the target prevents the labeled molecules to bind to the test line, leading to an inverse correlation between target concentration and fluorescence intensity on the test line. Adapted from [234] with permission. Copyright Centre National de la Recherche Scientifique (CNRS) and the Royal Society of Chemistry 2020.

Fig. 11

(A) Schematic of the triple thermocouple flow cell used. (B) Raw data HTM plot of the Rth over time for the addition of ST2 in FBS to a triple thermocouple set-up with one thermocouple functionalized with ST2 nanoMIPs (red), one functionalized with H-FABP nanoMIPs (blue), and one unfunctionalized thermocouple (black). (C) Plot of the Rth % change for the addition of ST2 in FBS to a triple thermocouple set-up with one thermocouple functionalized with ST2 nanoMIPs (red circles), one functionalized with H-FABP nanoMIPs (blue squares), and one unfunctionalized. Re-used with permission from [59], Copyright American Chemical Society 2019. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).