Early Cancer Detection by Single-molecule Imaging of Nucleocytoplasmic Tumor-specific Proteins in the Peripheral Circulation

Unmet Need / Invention Novelty: Due to lack of effective early detection modalities, ovarian and pancreatic cancers are rarely found until the disease has progressed and hence are highly lethal.  To overcome these limitations we report an ultra-sensitive microfluidic chip designed to bind and digitally quantify tumor-derived cancer proteins for an early disease detection and improved patient outcome.

Technical Details: Johns Hopkins researchers have developed SMAC (single-molecule analysis-and counting), a chip-based platform for the ultra-sensitive detection and quantification of nucleocytoplasmic proteins to diagnose early-stage cancer. SMAC integrates microfluidic herringbone structures coated with capture molecules that bind tumor-specific biomarkers found in patient serum. Target oncoproteins are concentrated using high velocity, closed-loop flow through the SMAC chip (actuated by a pump) that are then digitally imaged using fluorescence microscopy. These bound molecules are automatically quantified by a computer algorithm that discriminates between specific and non-specific binding events and calculates the number of fluorescence spots that score above a set threshold to provide ultra-sensitive early cancer detection. Preclinical trials using tumor-bearing and naïve control mice suggests that SMAC analysis of tumor-derived nucleoplasmic proteins can detect early stage cancer with 100% specificity and sensitivity.

Value Proposition:

• No need for biochemical signal amplification due to ultra-high sensitivity capture of target proteins on chip
• Entirely new way of bonding microfluidic devices suitable for SMD
• Digital molecule counting algorithm discriminates between on-off target detection
• SMAC analysis of tissue restricted biomarkers can indicate the anatomical location of the tumor

Looking for Partners to: Develop & commercialize the technology as early-cancer detection modality.

Stage of Development: Pre-clinical

Data Availability: Validated in multiple preclinical mouse models

Inventors: T.C. Wu, Chih-Ping Mao, Shih-Chin Wang, Jie Xiao, Chien-Fu Hung

Patent Status: Patent Pending US-2019-0308190

Publication(s): S.C. Wang, C.P. Mao, Y.P. Su, T.C. Wu, C.F. Hung, J. Xiao. Protein Detection in Blood with Single-Molecule Imaging. Biophys 116 (3), 465a
 

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