A hand-powered SERS-microfluidic chip for circulating tumor DNA detection from whole blood

Portable devices for rapid, automated and quantitative nucleic acid detection from whole blood is highly desirable for point-of-care (POC) molecular diagnostics. Conventional sequencing and polymerase chain reaction methods usually require trained personnel to deal with the time-consuming procedures, from sample purification to target amplification. To promote POC disease diagnosis and monitoring, we herein developed a hand-powered microfluidic chip for circulating tumor DNA (ctDNA) analysis from whole blood. On the one hand, the chip allowed rapid blood cell removal through a microfluidic filter trench. On the other hand, the ultrasensitivity of surface enhanced Raman spectroscopy (SERS) technique enabled amplification-free DNA mutation screening. Meanwhile, a finger-driven vacuum system was incorporated into the system, which achieved microfluidic pumping without external pumps, tubes or power sources. The developed SERS chip achieved fast screening of EGFR E746-A750 mutation in 35 min, reaching a limit of detection down to 100 fM in blood. Due to the simplicity, fast analysis, low cost and quantitative readout, the chip is expected to expand the availability of molecular diagnosis into resource-limited and bedside settings.