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: 7935216
• 负责人: Lev T Perelman
• 金额: $ 45.83万
• 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/7935216
• 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，如羊膜穿刺术、绒毛采样(CVS)和经皮脐血采样(PUBS)都是侵入性的，存在巨大的胎儿丢失风险。利用孕妇外周血中循环中的胎儿细胞进行无创性产前诊断，由于不会对胎儿构成危险而受到广泛关注。虽然有几种胎儿细胞类型已经成为目标，但搜索的重点是胎儿有核红细胞(FNRBC)。然而，由于母体血液中fNRBC的浓度很低，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和mNRBC的广泛适用的识别符，可靠地检测和分离足够数量的活细胞供临床使用仍然是一个巨大的挑战。胎儿NRBC与母体NRBC在核形态和血红蛋白分子结构上均有差异。最近，这位首席研究员和他在麻省理工学院的同事开发了生物医学光散射光谱(LSS)，并显示了其在不损害细胞的情况下光学探测核形态的独特能力。我们小组进一步改进了激光共聚焦吸收和散射光谱技术(CLASS)，并开发了能够监测小共焦体积的亚细胞细胞器的共聚焦吸收和散射光谱技术(CLASS)。这项研究计划的目的有两个。(1)我们将使用我们实验室开发的现有一类设备来识别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、简单和强大的光学技术，在同一仪器中结合普通显微镜和光学镊子，从而能够从母亲外周血样本中浓缩和回收完整的fNRBC。这将导致一种临床上有用的产前基因检测方法。 公共卫生相关性：在美国，每年约有50万孕妇接受羊膜穿刺术，众所周知，流产率约为0.5%。此外，据估计，在医生为其提供羊膜穿刺术的8名妇女中，有7人因风险而拒绝接受这一手术。该应用为羊膜穿刺术带来的危险提供了一种安全、非侵入性的解决方案。