Present cell-based techniques of prenatal diagnosis such as amniocentesis, chorionic villus sampling (CVS) and percutaneous umbilical blood sampling (PUBS) are invasive and present significant risks of fetal loss. Non-invasive prenatal diagnosis utilizing fetal cells circulating in maternal peripheral blood during pregnancy has received much attention since it poses no risk to the fetus. Although several fetal cell types have been targeted, the search has focused on fetal nucleated red blood cells (fNRBC). However, because of very low concentration of fNRBC in the maternal blood, interference by nucleated red blood cells of maternal origin (mNRBC) and the failure to find broadly applicable identifiers that can differentiate fNRBC from mNRBC reliable detection and isolation of viable cells in amounts sufficient for clinical use remains a monumental challenge. Fetal NRBC differ from maternal NRBC in both nuclear morphology and hemoglobin molecular structure. Recently the principal investigator and his colleagues at MIT have developed biomedical light scattering spectroscopy (LSS) and showed its unique ability to optically probe nuclear morphology without damaging cells. Our group has further advanced LSS and developed the confocal absorption and scattering spectroscopic technique (CLASS) capable of monitoring subcellular organelles in small confocal volumes. The objective of this research program is twofold. (1) We will use the existing CLASS equipment developed in our laboratory to identify fNRBC native optical biomarkers. (2) Based on these biomarkers, we will develop a fast, simple and robust optical technique which combines CLASS microscopy and optical tweezers in the same instrument and which will enable enrichment and recovery of intact fNRBC from a sample of maternal peripheral blood. This will lead to a clinically useful method for prenatal genetic testing.

Public Health Relevance

Amniocentesis is performed on approximately one-half million pregnant women in the United States each year, and is known to have an approximately 0.5% miscarriage rate. In addition it is estimated that 7 out of 8 women to whom amniocentesis is offered by their physician refuse the procedure because of the risk. This application offers a safe, noninvasive solution to the dangers associated with amniocentesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB006462-03
Application #
8122259
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Korte, Brenda
Project Start
2009-09-30
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
3
Fiscal Year
2011
Total Cost
$437,677
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Melo, Sonia A; Sugimoto, Hikaru; O'Connell, Joyce T et al. (2014) Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 26:707-21
Qiu, Le; Turzhitsky, Vladimir; Chuttani, Ram et al. (2012) Spectral Imaging with Scattered Light: From Early Cancer Detection to Cell Biology. IEEE J Sel Top Quantum Electron 18:1073-1083
Vitkin, Edward; Turzhitsky, Vladimir; Qiu, Le et al. (2011) Photon diffusion near the point-of-entry in anisotropically scattering turbid media. Nat Commun 2:587
Qiu, Le; Larson, Timothy A; Vitkin, Edward et al. (2010) Gold nanorod light scattering labels for biomedical imaging. Biomed Opt Express 1:135-142
Qiu, Le; Pleskow, Douglas K; Chuttani, Ram et al. (2010) Multispectral scanning during endoscopy guides biopsy of dysplasia in Barrett's esophagus. Nat Med 16:603-6, 1p following 606