Collaborative Research: Ultrasensitive Cancer Biomarker Detection on Biophotonic Chips

Brigham Young University, Provo UT

Investigators

Abstract

1159453/1159423 Schmidt/Hawkins The main goal of the proposal is to develop a chip that combines microfluidics with a sensitive fluorescence excitation and detection platform that relies on liquid-core waveguides. This lab-on-a-chip is designed for highly sensitive and specific detection of cell-free nucleic acids (CNAs) that are found in elevated concentrations within the bodily fluids of cancer patients. The high sensitivity of the proposed technology is expected to obviate the need for amplification that is currently required when performing traditional PCR assays for CNAs, which in turn increase the complexity and cost associated with this approach. The investigators propose to initially develop a multi-mode interferometric approach for fluorescence excitation in order to enhance the signal to noise ratio and to enable spectral multiplexing in order to enhance sensitivity and specificity. The second step involves integration of the silicon photonic layer with standard PDMS microfluidics layers for sample preparation and filtering. The integrated device will be tested initially using fluorescent beacons against viral nucleic acids associated with high-risk human papilloma virus (HPV) 18. In the final step, the platform will be tested using blood from 5 melanoma patients, a healthy human and a leukemia patient. Polymerase chain reaction (PCR) methods are the current gold standard in cell-free nucleic acids (CNA) detection and rely on amplifying the genomic material to produce a sufficiently large signal for optical readout.. The PIs propose to demonstrate and validate a biophotonic platform for multiplexed, amplification-free analysis of cell-free DNA. At its core will be liquid-core optical waveguides that have a limit of detection of single fluorescing molecules of DNA/RNA at clinically relevant concentrations. The project will address key innovations at all levels of the detection system, and, if successful, create a transformative step for cancer diagnosis, enabling non-invasive and quantitative analysis of biomarker panels from cell-free DNA.