Abstract
Early and personalized intervention in complex diseases requires robust molecular diagnostics, yet the simultaneous detection of diverse biomarkers—microRNAs (miRNAs), mutant DNAs, and proteins—remains challenging due to low abundance and preprocessing incompatibilities. We present Biomarker Single-molecule Chromato-kinetic multi-Omics Profiling and Enumeration (Bio-SCOPE), a next-generation, triple-modality, multiplexed detection platform that integrates both chromatic and kinetic fingerprinting for molecular profiling through digital encoding. Bio-SCOPE achieves femtomolar sensitivity, single-base mismatch specificity, and minimal matrix interference, enabling precise, parallel quantification of up to six biomarkers in a single sample with single-molecule resolution. We demonstrate its versatility in accurately detecting low-abundance miRNA signatures from human tissues, identifying upregulated miRNAs in the plasma of prostate cancer patients, and measuring elevated interleukin-6 (IL-6) and hsa-miR-21 levels in cytokine release syndrome patients. By seamlessly integrating multiomic biomarker panels on a unified, high-precision platform, Bio-SCOPE provides a transformative tool for molecular diagnostics and precision medicine.
Competing Interest Statement
The authors declare the following competing financial interest(s): M.T. and N.G.W. are inventors on multiple patent applications related to SiMREPS and Bio-SCOPE, and equity holders of aLight Sciences Inc., a startup company aiming to commercialize the presented technology.