Instrumenting the Fetal Membrane on a Chip

免疫系统第一次对病原体做出反应是在感染期间的子宫内。 在胎膜上。感染涉及胎膜是极其困难的 在子宫中学习，既因为难于接近，又因为性质复杂 母子之间的接口。因此，对妊娠相关疾病的研究 受益于胎膜的体外模型，即高度仪器化的胎儿 片上薄膜(IFMOC)。具体地说，这个研究项目的总体目标是 是应用多维分析技术和微流体工程设计 目的：明确体外胎膜感染的免疫反应生物学特征。 考虑到这些签名，我们这项从工作台到床边研究的最终长期目标 计划是开发一种简单、廉价和强大的芯片实验室系统，它将 允许在病程的早期对感染进行准确的病原学诊断 关于感染的系统性宿主反应信号。我们还将利用敏感和 区分急性感染和既往慢性感染的具体方法 感染和/或无症状的微生物定植。这项工作将基于一个 对传染病的人类系统生物学和意志有基本的了解 受益于芯片上器官微流体、光学、安培和 酶传感器和质谱仪。我们最初的多分析传感器配置文件是 专注于利用葡萄糖消耗和乳酸生产的细胞生物能量学和 我们的微细加工安培法测量超氧化物的氧化猝发 传感器以及由石英晶体微天平分泌的MIC-1蛋白质； 随后，这些特征将用离子迁移率-质谱学进行扩展 (IM-MS)。

The first time the immune system can respond to a pathogen is in utero during infections of the fetal membrane. Infection involving the fetal membranes is extremely difficult to study in utero, both because of inaccessibility and the nature of the complicated interface between mother and child. Thus, studies of pregnancy-related conditions benefit from an in vitro model of the fetal membrane, i.e., a highly instrumented fetal membrane on a chip (IFMOC). Specifically, the overarching goal of this research project is to apply multidimensional analytical technologies and microfluidics engineering design to define immune response biosignatures of infection in the in vitro fetal membrane. Given these signatures, our ultimate long-range goal for this bench-to-bedside research program is to develop a simple, inexpensive, and robust lab-on-a-chip system that will permit accurate etiologic diagnosis of infections early during the course of illness based on systemic host-response signatures of infection. We will also utilize sensitive and specific methodologies to differentiate acute infections from pre-existing chronic infections and/or asymptomatic microbial colonization. This work will be based on a fundamental understanding of the human systems biology of infectious diseases and will benefit from recent advances in organ-on-chip microfluidics, optical, amperometric, and enzymatic sensors, and mass spectrometry. Our initial multianalyte sensor profiles are focused on cellular bioenergetics using glucose consumption and lactate production and oxidative burst by superoxide production measured by our microfabricated amperometric sensors as well as MIC-1 protein secretion by the quartz crystal microbalance; subsequently these signatures will be expanded with ion mobility-mass spectrometry (IM-MS).