A microfluidic platform for high‐purity cell free DNA extraction from plasma for non‐invasive prenatal testing

Abstract Objectives Increase the yield and purity of cell‐free DNA (cfDNA) extracted from plasma for non‐invasive prenatal testing (NIPT) as inefficiencies in this extraction and purification can dramatically affect the sensitivity and specificity of the test. Methods This work integrates cfDNA extraction from plasma with a microfluidic chip platform by combining magnetic bead‐based extraction and electroosmotic flow on the microfluidic chip. Various wash buffers and voltage conditions were simulated using COMSOL Multiphysics Modeling and tested experimentally. Results When performing the first wash step of this assay on the microfluidic chip with 300 V applied across the channel there was a six‐fold increase in the A 260 / A 230 ratio showing a significant improvement ( p value 0.0005) in the purity of the extracted sample all while maintaining a yield of 68.19%. These values are critical as a high yield results in more sample to analyze and an increase in A 260 / A 230 ratio corresponds to a decrease in salt contaminants such as guanidinium thiocyanate which can interfere with downstream processes during DNA library preparation and potentially hinder the NIPT screening results. Conclusions This technique has the potential to improve NIPT outcomes and other clinically relevant workflows that use cfDNA as an analyte such as cancer detection.