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- Creator:
- Banerjee, Pavel , Ray, Sujay, Dai, Liuhan, Sandford, Erin, Chatterjee, Tanmay, Mandal, Shankar, Siddiqui, Javed, Tewari, Muneesh, and Walter, Nils G
- Description:
- 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 nanoscale 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 (the studies that collected these samples were approved by University of Michigan's Medical School Institutional Review Board HUM00043354, HUM00115179 and HUM00037879). By seamlessly integrating multiomic biomarker panels on a unified, high-precision platform, Bio-SCOPE provides a transformative tool for molecular diagnostics and precision medicine.
- Keyword:
- biomarker, fingerprinting, multiplexed detection, digital encoding, single molecule, multiomic, precision medicine
- Citation to related publication:
- Banerjee, Ray, Dai et al. Chromato-Kinetic Fingerprinting Enables Multiomic Digital Counting of Single Disease Biomarker Molecules. ACS Nano. Submitted.
- Discipline:
- Science
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- Creator:
- Chatterjee, Tanmay, Knappik, Achim, Sandford, Erin, Tewari, Muneesh, Choi, Sung Won, Strong, William B., Thrush, Evan P., Oh, Kenneth J., Liu, Ning, Walter, Nils G., and Johnson-Buck, Alexander
- Description:
- The sensitive measurement of specific protein biomarkers is important for medical diagnostics and research. However, existing methods for quantifying proteins use antibody probes that cannot distinguish between specific and nonspecific binding, limiting their sensitivity and specificity. This work establishes a method for distinguishing between specific binding to the target protein and nonspecific binding to assay surfaces using single-molecule kinetic measurements with dynamically binding probes. This is significant because it permits extremely sensitive protein measurements without requiring a high-affinity detection antibody or any washing steps, enabling streamlined and sensitive quantification of proteins even when no pair of high-quality, tightly binding antibodies is available.
- Keyword:
- biomarker detection, single molecule fluorescence, kinetic fingerprinting, total internal reflection microscopy, and super resolution microscopy
- Citation to related publication:
- Chatterjee, T., et al. Direct kinetic fingerprinting and digital counting of single protein molecules. Proc Natl Acad Sci USA, In Press.
- Discipline:
- Science
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- Creator:
- Hayward, Stephen L. , Lund, Paul E., Kang, Qing, Johnson-Buck, Alexander , Tewari, Muneesh, and Walter, Nils G.
- Description:
- This work contains the experimental data and associated analysis that are described in the research publication entitled "Ultra-specific and Amplification-free Quantification of Mutant DNA by Single-molecule Kinetic Fingerprinting". This work contains multiple zip files, each of which represents one of the principal experiment groups presented in the publication. Each experiment group contains movie and analysis files corresponding to various experimental conditions related to that experiment group.
- Keyword:
- Single Molecule Fluorescence, Super-Resolution Microscopy, Nucleic Acid Hybridization, T790M Mutation, Cytosine Deamination, SiMREPS, and single molecule kinetic fingerprinting
- Citation to related publication:
- https://pubs.acs.org/doi/10.1021/jacs.8b06685
- Discipline:
- Science