Microfluidic organic bioelectronic chips for efficient isolation of trophoblast cells using a combination of rational catenation and electrically controllable refining

Abstract

The non-invasive prenatal test (NIPT) has become the global standard for effective prenatal screening for newborn health care. Recently, there has been rapid growth in next-generation sequencing (NGS) technologies based on genomics using fetal nucleated red blood cells (fnRBCs) purified on chips; the performance of this approach can be competitive with cell-free fetal DNA (cffDNA) detection, but avoids the inherent drawbacks of cffDNA in NIPTs. To isolate the targeted cells from clinical samples, microfluidic device systems can be designed to minimize the use of reagents/samples and enhance the capture of targeted specimens by increasing the degree of contact between the targeted cells and chips. Nevertheless, sample refining remains a critical challenge affecting device performance. In this study, we developed poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) nanofiber–based film capacitors as organic bioelectronics interfaces (OBEIs). Efficient cell capture and release was possible through cyclic voltammetry (CV)–based charging/discharging operations, which varied the surface charge of the OBEIs. The combination of a microfluidic channel and film capacitor was engineered to refine 0.2% spike-in JEG-3 cells (a trophoblast cell line derived from the male) from 1 × 106 HeLa cells (a cervical cancer cell line derived from the female) into JEG-3 cells of 93.8% purity. This device platform displayed outstanding efficiency in the isolation of targeted cells, with a 1000-fold enrichment through three capture/release cycles of programmable CV operations, thereby providing high-purity targeted JEG-3 cells for use in a downstream real-time quantitative PCR (qPCR) assay. The qPCR and fluorescence in situ hybridization (FISH) data revealed that the off-chip-collected liquid biopsy sample could be used to identify the XY chromosome from the refined JEG-3 cells. This electrically controllable microfluidic OBEI platform appears to be a potential tool for enriching targeted cells from liquid biopsy samples and enhancing precision medicine applications based on cell-based NIPT technologies.