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“Digital Resolution Detection of miRNA and ctDNA Cancer Biomarkers using Photonic Crystal Biosensor Microscopy”
Prof. Brian T. Cunningham, PhD
Intel Alumni Endowed Chair of Electrical and Computer Engineering
University of Illinois at Urbana-Champaign
Woese Institute for Genomic Biology – Center for Genomic Diagnostics
Holonyak Micro and Nanotechnology Laboratory
Cancer Center at Illinois
ABSTRACT
Rapid and quantitative detection of exosomal micro-RNA (miRNA) and circulating tumor DNA (ctDNA) cancer biomarkers from blood with a simple workflow and inexpensive instrument will open opportunities for point of care therapy selection, therapy effectiveness monitoring, and remission monitoring. To address limitations of sensitivity, sequence specificity, cost, and complexity of existing approaches, we are developing ultrasensitive digital-resolution biomolecular sensing technologies combined with ultraselective isothermal, room temperature, enzyme-free molecular biology methods. A key to our digital resolution capability is utilization of quantum dot and gold nanoparticle tags that can be easily visualized with simple, inexpensive instruments when in contact with photonic metamaterial surfaces that amplify their signal through enhanced fluorescence or enhanced absorption. Although detection limits can reach 100 aM when a single target molecule is associated with a single nanoparticle tag, sensitivity can further be further improved through molecular biology methods that convert each biomarker into a large number of nanoparticle detection events using target recycling or CRISPR/Cas systems. For example, a novel Target Recycling Amplification Process (TRAP) that utilizes toehold probe strand displacement to release a miRNA target after detection, achieves 0.1 aM detection limits in a 1-pot, ~15 minute assay, with >3000:1 selectivity against single-base mismatches. For assays limited by diffusion, we are utilizing magnetic-plasmonic nanoparticle tags that are capable of reducing the incubation time to 1 minute. The approaches under development are intended to complement sequencing-based liquid biopsy to enable frequent, inexpensive, longitudinal molecular diagnostics for broad classes of nucleic acid and protein biomarkers involved in cancer and many other diseases.
ABOUT
Prof. Cunningham has been a faculty member in the department of Electrical and Computer Engineering and the department Bioengineering at the University of Illinois at Urbana-Champaign since 2004, following a 15-year career in Industry. Prof. Cunningham’s technical focus is the utilization of photonics for biosensing in applications that include life science research, diagnostics, environmental monitoring, and pharmaceutical screening. He has over 90 issued US patents and over 190 peer reviewed journal publications. He is a Fellow of NAS, IEEE, OSA, RSC, AAAS, and AIMBE.
Hosted by: Utkan Demirci, Ph.D.
Sponsored by: The Canary Center & the Department of Radiology
Stanford University – School of Medicine