Thermal detection of cardiac biomarkers H-FABP and ST2 using a molecularly imprinted nanoparticle-based multiplex sensor platform

Crapnell, R ORCID: https://orcid.org/0000-0002-8701-3933, Canfarotta, F, Czulak, J, Johnson, R, Betlem, K ORCID: https://orcid.org/0000-0002-5210-5619, Mecozzi, F, Down, MP, Eersels, K, Van Grinsven, B, Cleij, TJ, Law, R, Banks, CE ORCID: https://orcid.org/0000-0002-0756-9764 and Peeters, M ORCID: https://orcid.org/0000-0002-0429-8073 (2019) Thermal detection of cardiac biomarkers H-FABP and ST2 using a molecularly imprinted nanoparticle-based multiplex sensor platform. ACS Sensors, 4. pp. 2838-2845.

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Abstract

© 2019 American Chemical Society. This manuscript describes the production of Molecularly Imprinted Polymer nanoparticles (nanoMIPs) for the cardiac biomarkers heart-fatty acid binding protein (H-FABP) and ST2 by solid-phase synthesis, and their use as synthetic antibodies in a multiplexed sensing platform. Analysis by Surface Plasmon Resonance (SPR) shows that the affinity of the nanoMIPs is similar to that of commercially available antibodies. The particles are coated onto the surface of thermo-couples and inserted into 3D-printed flow cells of different multiplexed designs. We demonstrate it is possible to selectively detect both cardiac biomarkers within the physiologically relevant range. Furthermore, the developed sensor platform is the first example of a multiplex format of this thermal analysis technique which enables simultaneous measurements of two different compounds with minimal cross selectivity. The format where three thermocouples are positioned in parallel exhibits the highest sensitivity, which is explained by modelling the heat flow distribution with-in the flow cell. This design is used in further experiments and proof-of-application of the sensor platform is provided by measuring spiked fetal bovine serum samples. Due to the high selectivity, short measurement time, and low-cost of this array format, it provides an interesting alternative to traditional immunoassays. The use of nanoMIPs enables a multi-marker strategy, which has the potential to contribute to sustainable healthcare by improving reliability of cardiac biomarker testing.