Placenta-on-a-Chip Sensing Platform to Study Placental Malaria

项目总结/摘要 本研究的主要目的是建立具有实时感知能力的体外胎盘模型 人类胎盘病理学的研究，使用微流体，胎盘芯片和微传感技术。我们将 用恶性疟原虫胎盘疟疾模型展示拟议平台的能力。 重要病理事件，包括感染红细胞隔离（IE）、胎盘滋养层 将在真实的时间和流动条件下评价和监测炎症和灌注反应。 为了实现这一目标，我们提出了两个具体的目标，原型和评估这个平台。目标1：发展 具有阻抗传感的2D胎盘模型并评估胎盘疟疾的两个病理事件， 包括IE隔离和滋养层炎症反应在真实的时间。分析将包括 IE隔离的显微成像和IE通道的相应电阻抗感测， 粘附，以及滋养层完整性的电阻抗感测结合 细胞因子水平和免疫荧光显微镜检查以测试滋养层炎症反应。目标二是 开发一个具有电化学传感的3D胎盘模型，用于通过 胎盘屏障IE隔离的病理事件和受影响的胎盘屏障灌注反应将 与测量参数相关联。此外，在这两个目标中，我们将评估反 粘附干预，包括抗PfEMP 1抗体和已知的抗粘附分子， 病理性事件使用胎盘疟疾模型对该胎盘传感平台进行概念验证研究 对于未来的研究阐明胎盘疟疾病理学和其他胎盘疾病的分子细节是至关重要的。 以及开发新的治疗剂以预防或减轻胎盘炎性和不良反应。 灌注反应。

Project Summary/Abstract The primary goal of this project is to develop in vitro placental model with real-time sensing capabilities for study of human placental pathologies, using microfluidics, placenta-on-a-chip and microsensing technologies. We will demonstrate the capabilities of the proposed platform with Plasmodium falciparum placental malaria model. Important pathological events, including sequestration of infected erythrocytes (IE), placental trophoblast inflammatory and perfusion responses will be evaluated and monitored in real time and under flow conditions. To accomplish this goal, we propose two specific aims to prototype and evaluate this platform. Aim 1 is to develop a 2D placental model with impedimetric sensing and evaluate two pathological events of placental malaria, including IE sequestration and trophoblast inflammatory responses in real time. The analysis will include microscopic imaging of IE sequestration and corresponding electrical impedance sensing of IE passage and adhesion, as well as electrical impedance sensing of trophoblast integrity combined with measurements of cytokines levels and immunofluorescence microscopy to test for trophoblast inflammatory responses. Aim 2 is to develop a 3D placental model with electrochemical sensing for oxygen and glucose perfusion through the placental barrier. Pathological events of IE sequestration and impacted placental barrier perfusion response will be associated with the measured parameters. Furthermore, in both aims, we will evaluate the influences of anti- adhesion interventions, including anti-PfEMP1 antibodies and known anti-adhesion molecules on those pathological events. Proof-of-the-concept study of this placental sensing platform using placental malaria model is essential for future studies to elucidate the molecular details of placental malaria pathology and other placental pathologies, as well as to develop novel therapeutics to prevent or alleviate placental inflammatory and adverse perfusion responses.