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: 8321040
• 负责人: Lev T Perelman
• 金额: $ 47.95万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8321040
• 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; research study

Project Summary 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.

项目摘要 目前以细胞为基础的产前诊断技术，如胎盘穿刺、绒毛膜穿刺等， 血液采样（CVS）和经皮脐带血采样（PUBS）是侵入性的， 胎儿丢失的重大风险。利用循环中的胎儿细胞进行非侵入性产前诊断 妊娠期间的母体外周血由于其不构成风险而受到广泛关注 对胎儿的影响虽然已经有几种胎儿细胞类型被作为目标，但研究的重点是 胎儿有核红细胞（fNRBC）。然而，由于fNRBC的浓度非常低， 在母体血液中，母体来源的有核红细胞（mNRBC）的干扰， 未能找到可区分fNRBC与mNRBC的广泛适用的标识符 可靠地检测和分离足够临床使用的量的活细胞仍然是一个难题。 巨大的挑战 胎儿NRBC在核形态和血红蛋白方面与母体NRBC不同 分子结构最近，麻省理工学院的首席研究员和他的同事们 开发了生物医学光散射光谱（LSS），并显示出其独特的能力， 光学探测核形态而不损伤细胞。我们的团队进一步发展 激光共聚焦吸收和散射光谱技术（CLASS） 能够在小的共聚焦体积中监测亚细胞器。 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、稳健的光学技术 它将CLASS显微镜和光学镊子结合在同一仪器中， 能够从母体外周血样品中富集和回收完整的fNRBC。 这将导致产前基因检测的临床有用的方法。