Single cell prenatal testing of circulating trophoblasts using a the novel immunomagnetic Micro-Aperture Chip (IMAC) system

Project Summary The overall goal of this project is to develop a rapid non invasive and sensitive system for pre natal testing for fragile X syndrome FXS Asuragen will combine our unique and well characterized technologies for accurate detection of repeat expansions with Savran Technologiesandapos novel immunomagnetic Micro Aperture Chip IMAC system to enable prenatal testing of circulating fetal trophoblasts cTB isolated from maternal whole blood The combination of these systems will accomplish fetal cell selection using a novels system for antibody coupled magnetic fractionations that generates the substrate for highly sensitive and accurate sizing of FMR CGG repeats using Asuragenandapos s AmplideX reagents and workflows The American College of Obstetricians and Gynecologists clinical guidelines recommend prenatal testing for FXS Women who carry an FMR premutation or full mutation should be offered prenatal diagnosis because these women are at risk for having children with FXS Collectively more than one million women in the US may be carriers and those who are pregnant could benefit from noninvasive prenatal testing The system developed under proposal would enable prenatal screening using maternal blood samples reducing the risks associated with aminocentesis and chorionic villus sampling risk of miscarriage of up to in and permitting testing to be performed as early as weeks of gestation The specific aims are Aim Establish the feasibility of the IMAC system for immunomagnetic separation for trophoblast cells from cell lines spiked into whole blood for characterization by AmplideX PCR reagents in a workflow that includes Whole Gene Amplification WGA Aim Demonstrate characterization of IMAC fractionated cells from cell lines with well characterized genotypes across the full range of FMR allele specific sizing representing normal permutation and expanded alleles Aim Optimize performance of the IMAC WGA AmplideX workflow and demonstrate feasibility of prenatal testing by characterization of cTB from residual human blood specimens Project Narrative This project aims to advance pre natal testing of women at risk of having a child with fragile X syndrome by combining innovative reagents for repetitive sequence detection with a novel system for cell enrichment The combined system will enable accurate screening using maternal blood samples in order to reduce risk of miscarriage and provide screening much earlier in the pregnancy