Thermal Detection of Cardiac Biomarkers Heart-Fatty Acid Binding Protein and ST2 Using a Molecularly Imprinted Nanoparticle-Based Multiplex Sensor Platform

Robert D Crapnell, Francesco Canfarotta*, Joanna Czulak, Rhiannon Johnson, Kai Betlem, Francesco Mecozzi, Michael P Down, Kasper Eersels, Bart van Grinsven, Thomas J Cleij, Richard Law, Craig E Banks, Marloes Peeters*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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 thermocouples and inserted into 3D-printed flow cells of different multiplexed designs. We demonstrate that 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 modeling the heat flow distribution within 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. Because of 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 multimarker strategy, which has the potential to contribute to sustainable healthcare by improving the reliability of cardiac biomarker testing.

Original languageEnglish
Pages (from-to)2838-2845
Number of pages15
JournalACS sensors
Volume4
Issue number10
Early online date15 Oct 2019
DOIs
Publication statusPublished - Oct 2019

Keywords

  • DERIVATION
  • DIAGNOSIS
  • HFABP
  • POLYMERS
  • RECOGNITION
  • RISK STRATIFICATION
  • RULE
  • SENSITIVITY TROPONIN-T
  • SOLID-PHASE SYNTHESIS
  • SOLUBLE ST2
  • ST2
  • biosensors
  • cardiac biomarkers
  • heart-fatty acid binding protein (H-FABP)
  • heat-transfer method
  • molecularly imprinted polymer nanoparticles (nanoMIPs)
  • thermal detection

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