The microfluidic chip layers include a polydimethylsiloxane (PDMS)-coated glass slide, single PDMS pattern layer, thin glass coverslide and PDMS tubing adapter. (B) A single ultrathin pattern layer and hydration line effectively prevent evaporation through the permeable material. Source: Johns Hopkins University

Early detection of cancer biomarkers is the goal of the high-density profiling and enumeration by melt (HYPER-Melt) microfluidic platform.

The digital system identifies subtle DNA changes in cancer cells hiding among many healthy cells. Like all DNA, cancer DNA changes in response to its environment, and small changes, even a single nucleotide on a single gene, can give cancer DNA an advantage. Recognizing such changes early can inform physicians and expedite medical intervention.

HYPER-Melt focuses on manipulating and analyzing small volumes of fluid by separating blood samples into ever-smaller portions to simplify the analysis and identification of diseased from healthy DNA. The device digitizes and analyzes thousands of individual molecules.

The platform was applied to detect intermolecular heterogeneity of DNA methylation within the promoters of classical tumor suppressor genes. HYPER-Melt demonstrated detection limits as low as 1 methylated variant in two million unmethylated templates (0.00005%) of a classic tumor suppressor gene. The clinical potential of the platform was also demonstrated using a digital assay for NDRG4 -- a tumor suppressor gene that is commonly methylated in colorectal cancer, in liquid biopsies of healthy and colorectal cancer patients.

Researchers from Johns Hopkins School of Medicine, Johns Hopkins Institute for NanoBioTechnology, the University of Texas MD Anderson Cancer Center, the University of Pittsburgh and Johns Hopkins University contributed to this development, which is published in Nature Communications.