(143d) Multiplexed Metabolite Detection Using High-Q Metasurfaces and Modular DNA Aptamer Probes

Metabolite detection is crucial for understanding biochemical processes and pathways, and can facilitate more accurate and timely therapeutic intervention. For example, the metabolites cortisol, creatinine, ATP, and adenosine are associated with chronic stress, kidney dysfunction, and cardiovascular disease, but as of yet, no point-of-care test exists to quantitatively monitor their presence and abundance. Nanophotonic biosensors provide a platform for tracing these signature biomarkers, enabling precision health, early disease diagnosis, staging, and monitoring. Existing sensors based on plasmonic nanostructures face challenges such as limited sensitivity for low-concentration analytes and a lack of multimodal sensing capabilities.

Here, we demonstrate sensitive, multiplexed detection of these metabolites by integrating high-quality (high-Q) dielectric metasurfaces with spherical nucleic acid (SNA) reagents. Specifically, we design DNA sequences (aptamers) that undergo a structural change upon target metabolite binding. A split portion of this aptamer is bound as a single-strand to the SNA nanoparticle core (typically ~10nm diameter gold). Another portion of this split aptamer is bound to our resonant silicon nanophotonic antennas, termed VINPix¹, which can have quality factors in the thousands to tens of thousands. Upon the presence of target analytes, the DNA sequences on the metasurfaces and the SNAs interact with the target analyte molecules, resulting in the formation of a secondary DNA structure. This interaction effectively localizes the analytes and SNAs on the dielectric metasurfaces and creates localized hotspots, leading to a significant, visible-detectable resonance shift. Concurrently, the SNAs' attachment to the high-Q metasurfaces results in a visible color change of the metasurfaces, providing a visual signature of the biomarkers’ presence. We demonstrate the detection of clinically-relevant, nanoMolar concentrations of cortisol, creatinine, ATP, and adenosine. Additionally, we show how our modular VINPix arrays and SNA structures can be adapted to different biomarkers, for targeted and multiplexed detection of other molecules, including proteins, microRNAs, and ions. Finally, we show multiplexed detection of metabolites and proteins in clinical samples of urine. By quantifying multiple biomarkers in urine, our integrated approach provides vital health metrics like the urine albumin to creatinine ratio (uACR), a key indicator for kidney disease monitoring.

Reference:

1. Dolia, V., Balch, H., Dagli, S., Abdollahramezani, S., Delgado, H. C., Moradifar, P., ... & Dionne, J. A. (2023). Very-Large-Scale Integrated High-Q Nanoantenna Pixels (VINPix). arXiv preprint arXiv:2310.08065.