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

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 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 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. 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.

Screen Printed Electrode Based Detection Systems for the Antibiotic Amoxicillin in Aqueous Samples Utilising Molecularly Imprinted Polymers as Synthetic Receptors

“…In PBS, the R th of the MIP functionalised system stabilised at a value of 7.58 ± 0.05 • C/W. The increase in the R th value compared to previous work [18,21] was expected due to the presence of a thicker layer of polymer present on the electrode surface, which in turn will increase the resistance to heat flow through the interface. Upon the addition of 1 nM of amoxicillin an increase in the absolute R th value was observed from its baseline of 7.58 ± 0.05 • C/W to 7.67 ± 0.06 • C/W.…”

“…The aforementioned PID parameters can affect the power signal stability and therefore the sensitivity of the developed sensor. As such, the PID parameters were set to the optimized values determined for this heat source of P = 1, I = 14, D = 0.3 [21].…”

“…The disadvantage of working with MIP microparticles is the two-step (indirect) functionalisation process and the fact that the resulting electrodes are insulating and not compatible with traditional electrochemical detection. Recent work in our group has demonstrated that thermal analysis, in particular the Heat-Transfer Method (HTM), can provide an interesting alternative analysis technique that is easy to employ and provides rapid detection [21].…”

Diagnosis and prognosis for exercise-induced muscle injuries: from conventional imaging to emerging point-of-care testing

“…Besides, FABP can also be measured through thermal detection with deployment of highly affinitive nanoscale molecularimprinted nanoparticles, showing limit of detection of 4.18 ng mL À1 . 76 Apart from immunoassays, nucleic acid testing (NAT) has also been employed in portable devices for measurement of exercise-induced muscle injuries. NAT enables safe, sensitive and specic diagnoses of human diseases.…”

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

“…urine, blood, wastewater, soil samples, etc.) for a whole host of analytes [ [54] , [55] , [56] , [57] , [58] , [59] ]. Device sensitivity and limit of detection (LoD) is therefore situationally dependent on the technique and MIP employed.…”