Electrochemical Liquid Biopsy Assessing Placental Health

胎盘的健康对怀孕的幸福至关重要，对母亲和后代的一生都有影响。 健康人们认识到，胎盘植入、细胞发育和/或成熟中的畸变 不利地影响母体-胎儿的营养供应，对发育中的新生儿产生有害影响。 目前，可用于评估胎盘健康的临床工具包括超声（U/S）和次级超声（次级超声）。 对其他适应症（如胎儿非整倍性）进行的母体检测进行分析;这些包括血清 生物标志物、非侵入性产前检测（NIPT）和进入绒毛膜绒毛、羊膜的侵入性程序 液体或脐静脉血。然而，这些诊断方式中的许多（如果不是全部的话）都受到局限性的困扰 或者与次优的灵敏度、特异性和可预测性的准确性相关，或者与侵入性相关 可能出现并发症的测试因此，迫切需要非侵入性和易于部署的诊断 这些工具在预测胎盘健康方面具有高灵敏度和特异性。至少，部署能力 在妊娠早期进行筛查试验，以推荐更精细的成像来评估胎盘健康 是必要的.为此，我们对前瞻性队列研究的初步数据表明， 通过妊娠纵向收集的血浆和尿液可以分析cfDNA，cfRNA， 外泌体RNA/miRNA和来自胎盘的蛋白质。为了克服cfDNA的繁琐分析， cfRNA和外泌体RNA/微（mi）RNA/蛋白质，我们最近开发了一种新的 基于电磁和电化学生物传感器的技术称为“电化学液体活检”（eLB）， 用于从体液（例如尿液、唾液）样品中分离和鉴定RNA和蛋白质。这本小说 技术为我们提供了非侵入性研究关键转录物/蛋白质的能力， 敏感性、特异性和后续临床胎盘疾病的可预测性。基于这些收集的 根据初步数据，我们假设能够快速检测RNA/miRNA的非侵入性生物传感器， 尿中的蛋白质将允许以可靠的方式纵向检测胎盘健康。这样的工具， 最终可用于护理点检测，可以彻底改变实时监测胎盘健康， 准确的怀孕，允许及时引入新的干预措施（例如他汀类药物），以预防， 终止胎盘相关临床病症。为了验证这一假设，我们提出了两个具体目标：1） 开发并测试eLB设备，用于分离和同时测量多种转录物/蛋白质， 在正常妊娠期间纵向收集尿液。2)为了确定部署 用于检测正常和高风险之间的转录物/蛋白质差异的电化学生物传感器工具 为将来的护理点检测做准备，以实现实时非侵入性和快速 监测胎盘健康。通过比较尿液结果与配对血液样本进行验证，具有可预测性 通过胎盘MR成像、临床特征和胎盘组织病理学的存档收集进行评估。

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.