Detection of Methylated Cell-Free DNA for Diagnosis and Prognosis of Ovarian Cancer on an Integrated Microfluidic System

Methylated cell-free DNA (cfDNA) has been regarded as a novel indicator for early diagnosis and prognosis of ovarian cancer. However, analysis the methylation status of tumor suppressor genes in cfDNA remains challenging due to its extremely low concentration and lengthy, labor-intensive processes. In this study, an integrated microfluidic chip was reported to use beads coated with methyl CpG binding proteins and functional microfluidic devices which could implement (1) capture of methylated cfDNA in plasma and (2) semi-quantitative methylation-status analysis of tumor suppressor genes. The limit of detection could be as low as 2 pg/µL, which is two orders of magnitude lower than the previous work. Moreover, a dynamic range from 2 to 200 pg/µL of methylated cfDNA could be achieved. The whole process could be automated in 2 hr while only required 20 µL of plasma, indicating that this integrated microfluidic system may be utilized for early diagnosis and prognosis of ovarian cancer by using liquid biopsy.