Abstract

Molecular imprinting is a rapidly growing area of interest involving the synthesis of artificial recognition elements that enable the separation of analyte from a sample matrix and its determination. Traditionally, this approach can be successfully applied to small analyte (<1.5 kDa) separation/ extraction, but, more recently it is finding utility in biomimetic sensors. These sensors consist of a recognition element and a transducer similar to their biosensor counterparts, however, the fundamental distinction is that biomimetic sensors employ an artificial recognition element. Molecularly imprinted polymers (MIPs) employed as the recognition elements in biomimetic sensors contain binding sites complementary in shape and functionality to their target analyte. Despite the growing interest in molecularly imprinting techniques, the commercial adoption of this technology is yet to be widely realised for blood sample analysis. This review aims to assess the applicability of this technology for the point-of-care testing (POCT) of cardiovascular disease-related biomarkers. More specifically, molecular imprinting is critically evaluated with respect to the detection of cardiac biomarkers indicative of acute coronary syndrome (ACS), such as the cardiac troponins (cTns). The challenges associated with the synthesis of MIPs for protein detection are outlined, in addition to enhancement techniques that ultimately improve the analytical performance of biomimetic sensors. The mechanism of detection employed to convert the analyte concentration into a measurable signal in biomimetic sensors will be discussed. Furthermore, the analytical performance of these sensors will be compared with biosensors and their potential implementation within clinical settings will be considered. In addition, the most suitable application of these sensors for cardiovascular assessment will be presented.

Highlights

  • Detection and intervention of cardiovascular disease (CVD) continues to be a significant challenge for clinicians and healthcare providers worldwide

  • This method was incorporated in the design of a biomimetic sensor targeting Myo, cleaving the template protein into small amino acid residues prior to washing [66], it was reported that enzymatic digestion alone often does not ensure complete template removal [64,67]

  • This method relies upon targeting an epitope as the area against which the protein imprinted polymers (PIPs) is produced to bind, to adequately capture the protein of interest

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Summary

Introduction

Detection and intervention of cardiovascular disease (CVD) continues to be a significant challenge for clinicians and healthcare providers worldwide. This review aims to assess the use of imprinting techniques for the generation of biomimetic sensors targeting cardiac biomarkers and, subsequently, an evaluation of the potential application of these sensors for POCT. The inherent issues associated with protein imprinted polymers (PIPs) will be outlined in detail, in addition to examining the challenges of using protein templates and the characteristics that the derived sensors display These important aspects influence the potential applicability of this technology for POCT as there is a requirement to adhere to a pre-defined set of criteria for a diagnostic platform to be considered compatible with POC standards. The practical challenges of incorporating biomimetic sensors into cardiovascular assessment in clinical settings and the potential contribution of MIPs within POCT for CVD are discussed

Protein Detection
Challenges of Protein
Binding Kinetics
Solvent Compatability
Detection Techniques
Sandwich Complexes
Stimuli-Responsive Species
O4 —Iron
Classic ‘Label-Free’ Techniques
Multiplexed Detection
Feasability for Point-of-Care Testing
Biomimetic Sensors Analytical Performance
Evaluating Comparitive Performance
Clinical Considerations
MIPs for Point-of-Care Testing
10. Microfluidic
Findings
Conclusions
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