Novel Optical Technique for Recovery of Fetal Cells in Maternal Blood

用于回收母血中胎儿细胞的新型光学技术

基本信息

批准号：
7781472
负责人：
Lev T Perelman
金额：
$ 45.82万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7781472
关键词：
Adopted Adult Algorithms Amniocentesis Aneuploidy Attention Biological Markers Blood Blood Cells Blood specimen Bone Marrow Cells Centrifugation Characteristics Chorionic Villi Sampling Clinical Clinical Data Collection Coupled Density Gradient Centrifugation Detection Development Diagnosis Discipline of obstetrics Doctor of Philosophy Equipment Erythroblasts Evaluation Failure Female Fetus First Pregnancy Trimester Fluorescence Fluorescent in Situ Hybridization General Hospitals Genetic screening method Harvest Hemoglobin Individual Karyotype determination procedure Label Laboratories Lead Light-Scattering Spectroscopy Massachusetts Measurement Measures Methods Microscope Microscopy Modeling Molecular Analysis Molecular Structure Monitor Monoclonal Antibodies Morphology Noise Nuclear Optics Organelles Performance Peripheral Physicians Polymerase Chain Reaction Pregnancy Pregnant Women Prenatal Diagnosis Principal Investigator Procedures Pump Recovery Research Resolution Risk Robotics Sampling Screening procedure Signal Transduction Solutions Spectrum Analysis Spontaneous abortion Spottings System Techniques Test Result Testing Third Pregnancy Trimester Time Umbilical Blood Umbilical Cord Blood United States Woman absorption authority base cell injury cell type comparative genomic hybridization design experience fetal fetal medicine fetus cell instrument instrumentation laser tweezer light scattering mathematical model novel optical imaging peripheral blood prenatal programs prototype public health relevance research study

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：目前基于细胞的产前诊断技术，如羊膜穿刺术、绒毛膜绒毛取样（CVS）和经皮脐血取样（PUBS）是侵入性的，存在胎儿流产的重大风险。利用妊娠期间母亲外周血中循环的胎儿细胞进行的无创产前诊断由于对胎儿不构成风险而受到广泛关注。尽管已经针对几种胎儿细胞类型进行了研究，但研究重点是胎儿有核红细胞（fNRBC）。然而，由于母血中 fNRBC 的浓度非常低，受到母体有核红细胞 (mNRBC) 的干扰，并且未能找到能够区分 fNRBC 和 mNRBC 的广泛适用的标识符，可靠地检测和分离足够数量的活细胞临床应用仍然是一个巨大的挑战。胎儿 NRBC 在核形态和血红蛋白分子结构上都与母体 NRBC 不同。最近，麻省理工学院的首席研究员和他的同事开发了生物医学光散射光谱（LSS），并展示了其在不损伤细胞的情况下光学探测核形态的独特能力。我们课题组进一步推进了LSS，并开发了共焦吸收和散射光谱技术（CLASS），能够在小共焦体积内监测亚细胞细胞器。该研究计划的目标是双重的。 (1)我们将使用我们实验室开发的现有CLASS设备来识别fNRBC天然光学生物标志物。 (2) 基于这些生物标志物，我们将开发一种快速、简单且稳健的光学技术，该技术将 CLASS 显微镜和光镊结合在同一台仪器中，从而能够从母体外周血样本中富集和回收完整的 fNRBC。这将带来一种临床上有用的产前基因检测方法。公共健康相关性：美国每年约有 50 万孕妇进行羊膜穿刺术，已知流产率约为 0.5%。此外，据估计，医生向其提供羊膜穿刺术的 8 名女性中，有 7 名因风险而拒绝该手术。该应用程序为羊膜穿刺术相关的危险提供了一种安全、无创的解决方案。