Electrochemical Liquid Biopsy Assessing Placental Health

电化学液体活检评估胎盘健康

• 批准号: 10178068
• 负责人: Sherin U Devaskar
• 金额: $ 64.51万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10178068
• 关键词: Affect; Amniotic Fluid; Aneuploidy; Archives; Biological Assay; Biological Markers; Biosensor; Blood; Blood specimen; Cells; Child; Chorionic villi; Clinical; Collection; DNA Methylation; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Electromagnetics; First Pregnancy Trimester; Future; Gold; Health; High-Risk Pregnancy; Histopathology; Image; Intervention; Liquid substance; Magnetic Resonance Imaging; Measurement; Methods; MicroRNAs; Modality; Monitor; Mothers; Names; Nature; Newborn Infant; Nutrient; Performance; Perfusion; Personal Satisfaction; Placenta; Placenta Diseases; Placentation; Plasma; Pregnancy; Preparation; Procedures; Process; Proteins; RNA; Reverse Transcription; Sampling; Second Pregnancy Trimester; Sensitivity and Specificity; Serum; Specificity; Symptoms; Technology; Testing; Time; Tissues; Transcript; Translating; Ultrasonography; Urine; Validation; Venous; base; biobank; biomarker panel; cellular development; cohort; exosome; fetal; imaging modality; implantation; liquid biopsy; new technology; novel; offspring; point of care testing; point-of-care diagnostics; prenatal testing; prevent; prospective; protein biomarkers; saliva sample; screening; secondary analysis; synergism; tool; transcriptome sequencing; urinary

Placental health is essential for the well-being of pregnancy, with implications for mother and offspring's lifelong health. Recognition exists that aberrations in placental implantation, cellular development and/or maturation adversely affect the materno-fetal supply of nutrients with detrimental effects on the developing newborn. Currently the clinical tools available for assessing placental well-being consist of ultrasound (U/S), and secondary analysis of maternal tests performed for other indications, such as fetal aneuploidies; these include serum biomarkers, non-invasive prenatal testing (NIPT), and invasive procedures accessing chorionic villi, amniotic fluid or umbilical venous blood. However many if not all of these diagnostic modalities are plagued with limitations either related to suboptimal sensitivity, specificity and accuracy in predictability, or related to the invasive nature of testing with possible complications. Hence, there is a dire need for non-invasive and easy to deploy diagnostic tools that portray high sensitivity and specificity in predicting placental health. At a minimum, the ability to deploy a screening test early in 1st trimester towards recommending a more elaborate imaging to assess placental health is necessary. To this end, our preliminary data on a prospectively established cohort demonstrated that maternal plasma and urine collected longitudinally through pregnancy can be analyzed for a combination of cfDNA, cfRNA, exosome RNA/miRNA, and proteins, arising from placenta. To overcome the cumbersome analysis of cfDNA, cfRNA and exosome RNA/micro(mi)RNA/proteins by traditional methods, we have most recently developed an electromagnetic and electrochemical biosensor based technology named “electrochemical liquid biopsy” (eLB), for separation and identification of RNAs and proteins from bodily fluid (e.g. urine, saliva) samples. This novel technology provides us the ability in non-invasively investigating key transcripts/proteins that display high sensitivity, specificity and predictability of subsequent clinical placental disorders. Based on this collection of preliminary data, we hypothesize that a non-invasive biosensor capable of rapidly detecting RNAs/miRNAs and proteins in urine will allow longitudinal detection of placental health in a reliable manner. Such a tool if made ultimately available for point-of-care testing can revolutionize monitoring of placental health in real-time during pregnancy with accuracy, allowing timely introduction of novel interventions (e.g. statins) to prevent and thereby terminate placenta-associated clinical disorders. To test this hypothesis we propose two specific aims: 1) To develop and test an eLB device in separation and simultaneous measurement of multiple transcripts/proteins in urine collected longitudinally during normal pregnancies. 2) To determine the ability and validity in deploying the electrochemical biosensor tool in detecting transcript/protein differences between normal and high-risk pregnancies in preparation for future point-of-care testing in achieving real-time non-invasive and rapid monitoring of placental health. Validation by comparing urinary results to paired blood samples with predictability assessed by the archived collection of placental MR imaging, clinical features and placental histopathology.

胎盘健康对于怀孕的福祉至关重要，对母亲和后代的终生有影响 健康。认识到存在植入，细胞发育和/或成熟的畸变 不利地影响养分的母子供应对发展新生儿的不利影响。 目前 分析针对其他适应症的母体测试，例如胎儿非整倍性；这些包括串行 生物标志物，非侵入性产前测试（NIPT）和侵入性手术，可进入绒毛膜绒毛，羊膜 液体或脐静脉血。但是，许多这些诊断方式（如果不是全部）都受到限制的困扰 要么与次优敏感性，可预测性的特异性和准确性有关，要么与侵入性质有关 可能并发症的测试。因此，迫切需要非侵入性且易于部署诊断 描绘了高灵敏度和特异性的工具。至少可以部署能力 筛查测试在1st孕期初期，旨在推荐更精细的成像以评估占地健康 是必要的。为此，我们关于前瞻性同类的初步数据证明了孕产妇 可以分析通过怀孕纵向收集的血浆和尿液，以组合CfDNA，CFRNA， 外泌体RNA/miRNA和蛋白质，由plapeta产生。为了克服对CFDNA的繁琐分析， CFRNA和外泌体RNA/微（MI）RNA/蛋白质通过传统方法，我们最近开发了一个 电子和电化学生物传感器的技术称为“电化学液体活检”（ELB）， 为了分离和鉴定RNA和蛋白质与体液（例如尿液，唾液）样品的分离和鉴定。这本小说 技术为我们提供了非侵入性调查主要成绩单/蛋白质的能力 随后的临床占地疾病的敏感性，特异性和可预测性。基于这个集合 初步数据，我们假设一个非侵入性生物传感器能够快速检测RNA/miRNA和 尿液中的蛋白质将允许以可靠的方式纵向检测到斑点健康。这样的工具 最终可用于护理点测试可以彻底改变对位置健康的监测 具有准确性的怀孕，允许及时引入新颖的干预措施（例如他汀类药物），从而预防 终止与安置相关的临床疾病。为了检验这一假设，我们提出了两个具体目的：1） 开发和测试ELB设备的分离和简单测量多个转录本/蛋白 尿液在正常怀孕期间纵向收集。 2）确定部署的能力和有效性 电化学生物传感器工具检测正常和高风险之间的转录本/蛋白质差异 怀孕，准备未来的护理点测试，以实现实时非侵入性和快速测试 监测占地健康。通过将尿液结果与具有可预测性的配对的血液样本进行比较来验证 通过存档的Placenal MR成像，临床特征和位置组织病理学的收集进行评估。