Multiplexed and Continuous Monitoring of Metabolites Using High-Q Metasurfaces and Modular DNA Aptamer Probes

Chronic stress is a burgeoning global health issue, impacting nearly one-third of the population with severe consequences including cardiovascular diseases, autoimmune diseases, and certain cancers. The metabolites adenosine, dopamine, oestradiol, and cortisol are critical biomarkers for monitoring stress due to their known roles in physiological and psychological stress responses. Current methodologies, including mass spectrometry and fluorometric assays for detecting stress-related biomarkers, however, are limited by their need for laboratory settings, lengthy processing times, or lack of sensitivity, especially in complex biological matrices like sweat. Furthermore, existing technologies often do not support the simultaneous detection of multiple biomarkers, essential for comprehensive stress assessment. There is a pressing need for a more accessible, accurate, and rapid technology to enable continuous monitoring of stress-related metabolite biomarkers, to facilitate immediate and personalized therapeutic interventions.<br/><br/>Here, we demonstrate sensitive, multiplexed, and continuous monitoring 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 ~30 nm 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 electromagnetic hotspots, leading to significant optical scattering intensity changes. 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, picomolar concentrations of adenosine, dopamine, oestradiol, and cortisol in artificial sweat. Our method establishes a quantitative correlation between the concentration of target molecules and the observed resonance shifts. Moreover, the dense array of VINPix, combined with regenerative chip surfaces, and the application of microfluidic techniques and photochemistry, allows for the simultaneous and continuous detection of thousands of sensors targeting various metabolites. By facilitating continuous, non-invasive monitoring of stress biomarkers, this project could substantially improve individual health management and could lead to a reduction in the incidence and severity of stress-related health conditions.<br/><br/>Reference:<br/>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.