Value Proposition
· Simple, low-cost microfluidic tool that evaluates DNA methylation using non-invasive liquid biopsy samples.
· Allows for sensitive, specific evaluation of epigenetic biomarkers for early detection of cancer.
· Includes software and algorithms for improved diagnostic interpretation of DNA methylation analyses.
Unmet Need
· Early cancer detection improves treatment outcomes, reducing patient morbidity and mortality.
· Many cancers exhibit aberrant DNA methylation, a cancer-specific epigenetic biomarker that can be detected in non-invasive liquid biopsy samples.
· Therefore, there is a strong need to develop sensitive and cost-effective methods for detecting these epigenetic changes to support early cancer detection efforts.
Technology Description
· Researchers at Johns Hopkins have developed a microfluidics-based method for assessing locus-specific molecular heterogeneity of DNA methylation.
· This technology improves on the DREAMing platform (see publications below).
· This method can detect methylation abnormalities at low concentration, allowing for cancer detection in non-invasive samples such as blood, stool, sputum, and Pap specimens.
· Platform allows for parallel analyses of multiple samples.
· Includes software for semi-automated analysis and algorithms for identifying optimal methylation density thresholds to maximize biomarker performance.
Stage of Development
· Prototype
Publications
Pisanic, T. R., Athamanolap, P., Poh, W., Chen, C., Hulbert, A., Brock, M. V., Herman, J. G., & Wang, T. H. (2015). DREAMing: A simple and ultrasensitive method for assessing intratumor epigenetic heterogeneity directly from liquid biopsies. Nucleic Acids Research, 43(22). https://doi.org/10.1093/nar/gkv795
O’Keefe, C. M., Pisanic, T. R., Zec, H., Overman, M. J., Herman, J. G., & Wang, T. H. (2018). Facile profiling of molecular heterogeneity by microfluidic digital melt. Science Advances, 4(9). https://doi.org/10.1126/sciadv.aat6459
O'Keefe, C. M., Giammanco, D., Li, S., Pisanic, T. R., & Wang, T. H. J. (2019). Multilayer microfluidic array for highly efficient sample loading and digital melt analysis of DNA methylation. Lab on a Chip, 19(3), 444–451. https://doi.org/10.1039/c8lc01189c
O’Keefe CM, Kaushik AM, Wang TH. (2019). Highly Efficient Real-Time Droplet Analysis Platform for High-Throughput Interrogation of DNA Sequences by Melt. Anal Chem. 91(17):11275-11282. doi:10.1021/acs.analchem.9b02346
Miller, B. F., Pisanic II, T. R., Margolin, G., Petrykowska, H. M., Athamanolap, P., Goncearenco, A., Osei-Tutu, A., Annunziata, C. M., Wang, T. H., & Elnitski, L. (2020). Leveraging locus-specific epigenetic heterogeneity to improve the performance of blood-based DNA methylation biomarkers. Clinical Epigenetics, 12(1). https://doi.org/10.1186/s13148-020-00939-w
Zhao Y, O’Keefe CM, Hsieh K, et al. (2023). Multiplex Digital Methylation-Specific PCR for Noninvasive Screening of Lung Cancer. Adv Sci. 10(16):1-12. doi:10.1002/advs.202206518
