Point-of-Care Quantification of Serum Alpha-Fetoprotein for Screening Birth Defects in Resource-Limited Settings: Proof-of-Concept Study.

BACKGROUND: Maternal serum alpha-fetoprotein (MSAFP) concentration typically increases during pregnancy and is routinely measured during the second trimester as a part of screening for fetal neural tube defects and Down syndrome. However, most pregnancy screening tests are not available in the settings they are needed the most. A mobile device-enabled technology based on MSAFP for screening birth defects could enable the rapid screening and triage of high-risk pregnancies, especially where maternal serum screening and fetal ultrasound scan facilities are not easily accessible. Shifting the approach from clinic- and laboratory-dependent care to a mobile platform based on our point-of-care approach will enable translation to resource-limited settings and the global health care market. OBJECTIVE: The objective of this study is to develop and perform proof-of-concept testing of a lateral flow immunoassay on a mobile platform for rapid, point-of-care quantification of serum alpha-fetoprotein (AFP) levels, from a drop of human serum, within a few minutes. METHODS: The development of the immunoassay involved the selection of commercially available antibodies and optimization of their concentrations by an iterative method to achieve the required detection limits. We compared the performance of our method with that of commercially obtained human serum samples, with known AFP concentrations quantified by the Abbott ARCHITECT chemiluminescent magnetic microparticle immunoassay (CMIA). RESULTS: We tested commercially obtained serum samples (N=20) with concentrations ranging from 2.2 to 446 ng/mL to compare the results of our point-of-care assay with results from the Abbott ARCHITECT CMIA. A correlation of 0.98 (P<.001) was observed on preliminary testing and comparison with the CMIA. The detection range of our point-of-care assay covers the range of maternal serum AFP levels observed during pregnancy. CONCLUSIONS: The preliminary test results from the AFP test on the mobile platform performed in this study represent a proof of concept that will pave the way for our future work focused on developing a mobile device-enabled quad-screen point-of-care testing with the potential to enable the screening of high-risk pregnancies in various settings. The AFP test on the mobile platform can be applied to enable screening for high-risk pregnancies, within a few minutes, at the point of care even in remote areas where maternal serum tests and fetal ultrasound scans are not easily accessible; assessment of whether clinical follow-up and diagnostic testing may be needed after a positive initial screening evaluation; and development of surveillance tools for birth defects.