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

• 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
• 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

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，如胎盘穿刺术、绒毛膜绒毛取样（CVS）和经皮脐带血取样（PUBS）是侵入性的，存在显著的胎儿丢失风险。利用孕妇外周血中循环的胎儿细胞进行非侵入性产前诊断，由于对胎儿没有风险，因此受到广泛关注。虽然已经针对几种胎儿细胞类型，但搜索集中在胎儿有核红细胞（fNRBC）上。然而，由于母体血液中fNRBC的浓度非常低，母体来源的有核红细胞（mNRBC）的干扰以及未能找到能够区分fNRBC与mNRBC的广泛适用的标识符，以足以用于临床使用的量可靠地检测和分离活细胞仍然是巨大的挑战。 胎儿NRBC与母体NRBC在核形态和血红蛋白分子结构上均不同。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），并显示了其独特的能力，在不损伤细胞的情况下光学探测核形态。我们的小组进一步推进了LSS，并开发了共聚焦吸收和散射光谱技术（CLASS）能够监测小共聚焦体积的亚细胞器。这项研究计划的目的是双重的。(1)我们将使用我们实验室开发的现有CLASS设备来鉴定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，简单和强大的光学技术，在同一仪器中结合CLASS显微镜和光学镊子，这将使富集和完整的fNRBC从母体外周血样本的回收。这将导致产前基因检测的临床有用的方法。 公共卫生关系：在美国，每年约有50万孕妇接受羊膜穿刺术，流产率约为0.5%。此外，据估计，在医生建议进行子宫颈穿刺术的8名妇女中，有7名因风险而拒绝接受手术。该应用程序提供了一个安全的，非侵入性的解决方案，以危险与穿刺术。