Instrumenting the Fetal Membrane on a Chip

在芯片上检测胎儿膜

基本信息

批准号：
10430227
负责人：
DAVID E CLIFFEL
金额：
$ 63.11万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10430227
关键词：
3-Dimensional Amniotic Fluid Anatomy Anti-Inflammatory Agents Bacteria Bacterial Infections Bioenergetics Cause of Death Cells Cervix Uteri Child Collection Communicable Diseases Connective Tissue Consumption Crystallization Data Development Devices Diagnosis Disease Disease Outcome Etiology Event Failure Fetal Development Fetal Membranes Fetus Glucose Goals Human Immune Immune response Immune system In Vitro Infection Inflammation Inflammation Mediators Inflammatory Inflammatory Response Innate Immune Response Intervention Invaded Knowledge Lab-On-A-Chips Lead Liquid substance Mass Spectrum Analysis Maternal and Child Health Measures Membrane Membrane Biology Metalloproteases Methodology Microbe Microfluidic Microchips Microfluidics Modeling Molecular Mothers Nature Optics Organ Paracrine Communication Participant Partner in relationship Pathogenesis Patients Phagocytosis Placenta Play Population Pregnancy Pregnancy Complications Premature Birth Prevention Preventive Problem Solving Process Production Prognostic Marker Protein Secretion Quartz Reproductive Health Research Research Project Grants Resolution Respiratory Burst Role Shapes Side Stromal Cells Structure Superoxides System Systems Biology Technology Testing Therapeutic Time Tissue Model Tissues Vagina Work acute infection adverse outcome base bench to bedside biological adaptation to stress biosignature cell type chronic infection defined contribution diagnostic biomarker engineering design fetal fetal infection human model human tissue improved in utero in vitro Model in vivo innovation insight instrument intraamniotic infection ion mobility macrophage metabolomics microbial microbial colonization neonatal infection neonate organ on a chip pathogen preservation preterm premature rupture of membranes prevent programs sensor stillbirth

项目摘要

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).

免疫系统第一次可以在感染期间对病原体反应的病原体胎膜。涉及胎儿膜的感染极为困难在子宫内研究，既是由于难以接近和复杂的性质母子之间的界面。因此，研究与妊娠有关的情况受益于胎儿膜的体外模型，即高度仪器的胎儿芯片上的膜（IFMOC）。具体而言，该研究项目的总体目标是应用多维分析技术和微流体工程设计定义体外胎儿膜中感染的免疫反应生物签名。鉴于这些签名，这是我们这项基准对床的最终远程目标程序是为了开发一个简单，廉价且健壮的实验室芯片系统，该系统将允许在基于疾病的过程中早期对感染的准确诊断在系统性宿主 - 响应感染的特征上。我们还将利用敏感和特定方法是区分急性感染与先前存在的慢性感染感染和/或无症状的微生物定植。这项工作将基于对传染病的人类系统生物学的基本了解，将从芯片微流体，光学，安培计量学和酶传感器和质谱法。我们最初的多体分析物传感器曲线是使用葡萄糖消耗和乳酸产生和通过我们的微生物测量法测量的超氧化物产生的氧化爆发石英晶体微生体的传感器以及MIC-1蛋白分泌；随后，这些特征将通过离子迁移率质谱法扩展（IM-MS）。