Preterm birth, preeclampsia, and fetal growth restriction are major causes of fetal and maternal morbidity and mortality. There is increasing evidence that dysregulation of placental function is associated with these disorders, and that the pathologic processes leading to them long precede their clinical manifestations. Therefore, the ability to accurately, rapidly, and safely detect various forms of placental dysfunction early in pregnancy may enable discovery and clinical use of novel biomarkers of pregnancy complications. Currently available strategies for prediction of these adverse pregnancy outcomes suffer from low sensitivity and specificity and/or are unfeasible for broad implementation, due to the need for expensive equipment, specialized expertise, or long turnaround times. This project aims to develop a magnetic nanosensor-based platform for measurement of analytes in the maternal blood that reflect placental function, which can be used to discover novel predictive biomarkers and make them universally available. The project team includes the expertise in maternal fetal medicine (Dr. Laurent), biomarker discovery (Drs. Laurent and Boniface), assay design (Drs. Lo and Boniface), and biosensors and instrument design (Drs. Hall and Lo).
Aim 1 will focus on development of a magnetic immunoassays (MIAs) targeting known biomarkers of placental function (PAPP-A, ?HCG, AFP, INHA, sFLT and PLGF) and two novel analytes from a clinical mass-spectrometry-based assay for prediction of spontaneous preterm birth developed by Sera Prognostics (IGFBP4 and SHBG), and validation of these MIAs against existing clinical ELISA- and mass spectrometry-based tests.
Aim 2 will include development, testing, and validation of magnetic nanosensor-based miRNA assays (MamiRAs), which will be adapted from a highly sensitive and specific optical PCR-free miRNA assay developed by the Lo group. Replacing the fluorescent quantum dots in the optical assay with magnetic nanoparticles will enable the MamiRAs to be read on the same device as the MIAs for proteins. After initial proof-of-concept studies, we will develop MamiRAs that interrogate a novel set of 21 miRNAs in maternal serum that Dr. Laurent has found to be highly predictive of placental dysfunction. If successful, this project will produce a versatile magnetic nanosensor-based platform for sensitive and specific quantification of a variety of analyte types, which will not only enable development of novel strategies for management and treatment of pregnancy complications, but can also be applied to other clinical and biological systems. Moreover, the platform is amenable to miniaturization, which will enable clinical tests to be performed at the point-of-care, allowing the treating physician to have immediate access to the test results, and enabling testing, interpretation and management/treatment recommendations to be done at the same clinic visit. The ability to test and treat in the same visit will improve the efficiency of the system and eliminate the risk of delayed treatment or loss-to-followup.
The primary goal of this project is to develop magnetic nanosensor-based device that will be to quantify the levels of pregnancy-associated proteins and miRNAs in maternal blood. This project is relevant to public health because altered levels of these analytes are linked to pregnancy complications that threaten the welfare of mothers and babies, including preeclampsia and preterm birth. If successful, this project will allow us to accurately predict adverse pregnancy and postnatal outcomes.
