Electrochemical Liquid Biopsy Assessing Placental Health

电化学液体活检评估胎盘健康

• 批准号: 10646207
• 负责人: Sherin U Devaskar
• 金额: $ 63.6万
• 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/10646207
• 关键词: Affect; Amniotic Fluid; Aneuploidy; Archives; Biological Assay; Biological Markers; Biosensor; Blood; Blood specimen; Body Fluids; Cells; Child; Chorionic villi; Clinical; Collection; DNA Methylation; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Electromagnetics; First Pregnancy Trimester; Future; Health; High-Risk Pregnancy; Histopathology; Image; Intervention; Ischemia; 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; Recommendation; Reverse Transcription; Saliva; Sampling; Second Pregnancy Trimester; Sensitivity and Specificity; Serum; Specificity; Symptoms; Technology; Testing; Time; Tissues; Transcript; Translating; Umbilicus; Urine; Validation; Venous; biobank; biomarker panel; cellular development; cohort; diagnostic tool; 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; rapid detection; screening; secondary analysis; synergism; tool; transcriptome sequencing; ultrasound; 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.

胎盘健康对于怀孕期间的健康至关重要，对母亲和后代的一生都有影响 认识到胎盘着床、细胞发育和/或成熟存在异常。 对母胎营养供应产生不利影响，从而影响新生儿发育。 目前，可用于评估胎盘健康的临床工具包括超声（U/S）和二次超声（U/S）。 对其他适应症（例如胎儿非整倍体）进行的母体检测分析，其中包括血清； 生物标志物、无创产前检测 (NIPT) 以及侵入绒毛膜、羊膜的侵入性手术 然而，许多（如果不是全部）这些诊断方式都存在局限性。 要么与可预测性的次优敏感性、特异性和准确性有关，要么与侵入性有关 因此，迫切需要非侵入性且易于部署的诊断。 在预测胎盘健康方面具有高灵敏度和特异性的工具至少具有部署能力。 在妊娠早期进行筛查测试，以推荐更精细的成像来评估胎盘健康 为此，我们对前瞻性队列的初步数据表明，母亲 可以对怀孕期间纵向收集的血浆和尿液进行 cfDNA、cfRNA、 来自胎盘的外泌体 RNA/miRNA 和蛋白质 为了克服 cfDNA 的繁琐分析， 通过传统方法进行 cfRNA 和外泌体 RNA/micro(mi)RNA/蛋白质，我们最近开发了一种 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）样本中分离和鉴定 RNA 和蛋白质。 技术为我们提供了非侵入性研究显示高水平的关键转录本/蛋白质的能力 基于该收集的后续临床胎盘疾病的敏感性、特异性和可预测性。 初步数据显示，我们寻求一种能够快速检测 RNA/miRNA 的非侵入性生物传感器， 如果制造出这样的工具，尿液中的蛋白质将能够以可靠的方式纵向检测胎盘健康状况。 最终可用于现场护理测试，可以彻底改变妊娠期间胎盘健康的实时监测 准确地怀孕，允许及时引入新的干预措施（例如他汀类药物）来预防，从而 为了检验这一假设，我们提出了两个具体目标：1) 终止胎盘相关的临床疾病。 开发和测试 eLB 设备，用于分离和同时测量多种转录物/蛋白质 正常妊娠期间纵向收集的尿液 2) 确定部署的能力和有效性。 电化学生物传感器工具，用于检测正常和高风险之间的转录物/蛋白质差异 为未来的妊娠现场检测做好准备，实现实时、无创、快速 通过比较尿液结果与可预测的配对血液样本来监测胎盘健康。 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。

项目成果

Utility of In Vivo Magnetic Resonance Imaging Is Predictive of Gestational Diabetes Mellitus During Early Pregnancy.

体内磁共振成像可预测妊娠早期妊娠糖尿病。

• 发表时间: 2023-01-17
• 作者: Lee, Brian;Janzen, Carla;Wu, Holden;Vangala, Sitaram S;Devaskar, Sherin U;Sung, Kyunghyun
• 通讯作者: Sung, Kyunghyun

Circulating extracellular vesicles exhibit a differential miRNA profile in gestational diabetes mellitus pregnancies.

循环细胞外囊泡在妊娠期糖尿病妊娠中表现出不同的 miRNA 谱。

• 发表时间: 2022
• 影响因子: 3.7
• 作者: Thamotharan, Shanthie;Ghosh, Shubhamoy;James;Lei, Margarida Y Y;Janzen, Carla;Devaskar, Sherin U
• 通讯作者: Devaskar, Sherin U

Pediatrician's role in vaccinating children and families for COVID-19: no one left behind.

儿科医生在为儿童和家庭接种 COVID-19 疫苗方面的作用：没有人掉队。

• 发表时间: 2021-12
• 影响因子: 3.6
• 作者: de St Maurice, Annabelle;Cheng, Tina L;Devaskar, Sherin U;Pediatric Policy Council
• 通讯作者: Pediatric Policy Council

Application of Multiparameter Quantitative Magnetic Resonance Imaging in the Evaluation of Graves' Ophthalmopathy.

多参数定量磁共振成像在格雷夫斯眼病评估中的应用。

• 发表时间: 2023-10
• 作者: Li, Zhangfang;Luo, Yaosheng;Feng, Xiaoting;Zhang, Qing;Zhong, Qiang;Weng, Chanyan;Chen, Zhi;Shen, Jie
• 通讯作者: Shen, Jie

Extracellular vesicles and their role in gestational diabetes mellitus.

细胞外囊泡及其在妊娠糖尿病中的作用。

• DOI: 10.1016/j.placenta.2021.02.012
• 发表时间: 2021-09-15
• 期刊: Placenta
• 影响因子: 3.8
• 作者: James-Allan LB;Devaskar SU
• 通讯作者: Devaskar SU