Development of an IoT-integrated digital droplet nucleic acid detection system for liquid biopsy screening

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor[1]. Effective treatments on the early-stage glioblastoma may improve its poor survival rate and poor prognosis[2]. In this pilot study, a low copy number of nucleic acid detection system using a high-throughput microfluidic droplet imaging device was developed to achieve the specific nucleic acid detection of extracellular vesicles (EVs). Our aim is to realize an inexpensive liquid biopsy tool for the early detection of GBM using human plasma and cerebrospinal fluid (CSF). Our results demonstrate that: (a) the fabricated microfluidic chip (10 mm × 25 mm) can produce more than 25,000 droplets within 3 minutes. The average volume of generated droplets is 0.043 nanoliter (nL); (b) the entire droplet image can be acquired within 15 seconds without using the conventional stitching technique; (c) additionally, we automated the droplet image processing to determine the absolute copy number and concentration of nucleic acid samples. This portable IoT-integrated digital droplet nucleic acid sensing system provide an inexpensive and affordable optical biopsy screening tool for the early diagnosis and treatment surveillance of brain tumors. Our work can be applied into other diseases, such as colorectal cancer, pancreatic cancer and breast cancer.