Abstract: Biological systems function through intricate yet well-balanced biomolecular processes. Probing critical bioanalytes, such as protein biomarkers, therapeutic drugs, and metabolites, provides a powerful lens into human health and bioprocess performance, as even trace amounts of emerging biomarkers or subtle variations in process parameters can signal pathological changes or system malfunctions. However, achieving high measurement accuracy and precision remains challenging due to limitations in sensitivity, specificity, and robustness of existing bioanalytical techniques.

Surface-enhanced Raman spectroscopy (SERS) offers exquisite molecular specificity, single-molecule sensitivity, and high spatial resolution, making it a compelling candidate for translational biophotonic diagnostics. Yet, its adoption as a quantitative measurement tool is hindered by the SERS uncertainty principle and substantial intensity fluctuations arising from heterogeneous SERS hotspot distribution, non-uniform analyte deposition, a short field decay length, and dynamic analyte-metal interactions.

To address these challenges, in this talk, I will present three complementary and progressively sophisticated spectroscopic platforms to advance translational biophotonic diagnostics by leveraging plasmonic and quantum polaritonic principles.

First, I will introduce a SERS frequency shift-based single-antibody immunoassay, which decouples measurement signals from intensity fluctuations by transducing molecular recognition into SERS frequency shifts. Its clinical relevance has been validated under stringent industrial detection protocols provided by Beckman Coulter Diagnostics through robust detection of thyroid-stimulating hormones in patient samples, ultrasensitive detection of an acute myocardial infarction biomarker panel, and high-precision spectrally super-resolved colloidal SERS detection of a protein biomarker panel spanning endocrine, cardiovascular, and hemostatic disorders.

Second, I will present a label-free digital SERS assay, which converts fluctuating spectra into binary “ON/OFF” signals, thereby mitigating intensity variations and minimizing false positives. Integration with deep learning substantially broadens analyte coverage and enables precise, rapid, and ultrasensitive monitoring of chemically defined AMBIC cell culture media and urine neurotransmitters. Its industrial translational potential has been validated through projects supported by AMBIC, Cohen Translational Engineering Fund, and Maryland Innovation Initiative Technology Assessment Grant, with endorsements from Boehringer Ingelheim, Genentech, AstraZeneca, and NIST.

Third, I will introduce quantum polaritonic biosensing, which provides a fundamentally new strategy to interrogate molecules by dressing molecular states with cavity photons under ambient conditions. The resulting Rabi doublet peak splitting marks a substantial enhancement in sensitivity and specificity when compared to classical sensing, and provides quantum vibro-polaritonic fingerprints of molecules, paving the way for quantum vibro-polaritonic spectroscopy for accurate molecular profiling of therapeutic drugs.

Together, these advances establish new pathways for practical biophotonic diagnostics by integrating nanoengineering, artificial intelligence, plasmonics, and quantum optics.

N/B: Please note that this event is not being held on our usual colloquium day, which is Monday.