Timely detection of cardiac biomarkers is needed to diagnose acute myocardial infarction, implement the appropriate early treatment, and significantly reduce the chance of mortality. Ideally, for maximizing patient impact, a point of care device needs to be designed that is fast, sensitive, reliable, and small enough to be used in the ambulance and emergency department. Surface enhanced Raman spectroscopy (SERS) is a sensitive optical technique that can potentially be used to quantify the cardiac biomarkers of interest. In this work, silver nanoparticles were functionalized with a Raman reporter molecule and human cardiac Troponin I (cTnI) as an essential component of binding assays. Aggregated nanoparticles with the Raman reporter molecules were encapsulated in a silica shell to form SERS hotspots. Besides having a specific Raman spectra and binding affinity to cardiac Troponin I antibodies, the nanoparticles were designed to exhibit stability by using silica and polyethylene glycol (PEG) as part of the bioconjugation strategy. The specific narrow peaks from the Raman reporter molecule SERS signal allow for potential multiplexing capabilities as different Raman reporter molecules can be used in functionalized nanoparticles with different cardiac biomarkers. The SERS spectrum of the functionalized nanoparticles was measured to assess its potential to be used in an assay.
Competitive binding assays based on the protein Concanavalin A (ConA) have been proposed as potential sensors for
continuous glucose monitoring applications. However, ConA-based assays in the literature have primarily displayed a
lack of sensitivity or a lack of repeatability in their glucose response. This work explores this apparent trade-off by
separating the measured glucose response into the recognition and fluorescence transduction mechanisms. The
recognition responses are modeled for typical competing ligands/assays used in the literature, and they are combined
with an optimized fluorescence approach to yield expected fluorescent glucose responses. Because aggregation is
known to increase the apparent affinity between multivalent ligands and multivalent receptors, preliminary models are
generated for assays that were initially optimized with multivalent ligands but increase in affinity over time. These
models accurately predict the low sensitivity for monovalent ligands and the lack of repeatability in the responses with
multivalent ligands as seen in the literature. This subsequently explains the aforementioned trade-off no matter the
optical approach.
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