A microfluidic platform for the high-throughput isolation circulating fetal trophoblasts for non-invasive prenatal testing

Biofluidica, Inc, San Diego CA

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Abstract

Building on a history of success in developing microfluidic platforms to advance individualized cancer care and treatment, BioFluidica, Inc. is now focusing its efforts on developing a microfluidic approach for non-invasive prenatal testing (NIPT) to identify genetic abnormalities and inform prenatal and perinatal care. Maternal blood contains a host of fetal biomarkers that can be used for non-invasive prenatal testing (NIPT). Current commercial NIPT approaches rely on the isolation and molecular analysis of circulating cell free fetal DNA. These tests have demonstrated success in reducing the risks associated with amniocentesis and other invasive approaches. However, due to the high background of maternal cell free DNA in circulation, current NIPT approaches cannot detect single copy genetic abnormalities that lead to most birth defects and spontaneous miscarriage. To meet this need, BioFluidica is developing a cell-based microfluidic approach to capture whole, intact fetal trophoblast cells that are in maternal circulation. Because each trophoblast carries a complete and single copy of the fetal genome, the technologies to achieve efficient and cost-effective isolation of this unique cell type holds the key to advancing risk-free, non-invasive, and comprehensive prenatal genomic testing and diagnostics. Building on our Liquid Scan technology that is advancing individualized, patient-specific cancer care and treatment, the objective of this Phase I proposal is to develop a microfluidic platform for the isolation and enrichment of circulating trophoblasts from maternal blood. Leveraging our previous success will evaluate the potential of several cell surface antigens to target for microfluidic capture (Aim 1). We will optimize microfluidic capture efficiency and demonstrate the feasibility of downstream cell and molecular analysis of captured cells (Aim 2). We will demonstrate the preclinical utility of the microfluidic device with the capture of circulating trophoblasts from maternal blood collected during pregnancy with a high recovery rate and purity (Aim 3). Our long term goal is the development of a fully integrated and automated microfluidic platform for the enrichment of fetal trophoblast cells with high recovery and reproducibility. The platform will provide high specificity and throughput, and be cost effective as a commercially viable technology.