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Instrumenting the Fetal Membrane on a Chip

在芯片上检测胎儿膜

基本信息

批准号：
10651647
负责人：
DAVID E CLIFFEL
金额：
$ 61.85万
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 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10651647
关键词：
3-Dimensional Acceleration Amniotic Fluid Anatomy Anti-Inflammatory Agents Bacteria Bacterial Infections Bioenergetics Cause of Death Cells Cervix Uteri Child Collection Communicable Diseases Connective Tissue Consumption Data Development Devices Diagnosis Dimensions Disease Disease Outcome Equilibrium Etiology Event Failure Fetal Development Fetal Membranes Fetus Glucose Goals Human Immune Immune response Immune system In Vitro Individual Infection Inflammation Inflammation Mediators Inflammatory Inflammatory Response Innate Immune Response Intervention Invaded Knowledge Lab On A Chip Liquid substance Macrophage 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 Perfusion Phagocytosis Placenta Play Population Pregnancy Pregnancy Complications Premature Birth Prevention Preventive 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 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 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).

免疫系统第一次对病原体做出反应是在子宫内感染期间胎儿的膜。感染涉及胎膜是非常困难的，在子宫内的研究，既因为难以接近和复杂的性质，母亲和孩子之间的互动因此，对妊娠相关疾病的研究受益于胎膜的体外模型，即，一个高度仪器化的胎儿膜上芯片（IFMOC）。具体来说，这个研究项目的首要目标是应用多维分析技术和微流体工程设计以确定体外胎膜中感染的免疫应答生物特征。鉴于这些特征，我们这项从实验室到临床研究的最终长期目标计划是开发一个简单，廉价，强大的芯片实验室系统，将允许在疾病过程的早期进行准确的病原学诊断，感染的系统性宿主反应特征我们还将利用敏感和区分急性感染与先前存在的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的基本理解，受益于器官芯片微流体、光学、电流分析和酶传感器和质谱仪。我们最初的多分析物传感器配置文件是专注于使用葡萄糖消耗和乳酸盐生产的细胞生物能量学，通过我们的微型安培测量超氧化物产生的氧化爆发传感器以及MIC-1蛋白分泌的石英晶体微天平; 随后，这些特征将用离子迁移率质谱法进行扩展（IM-MS）。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Trace Oxygen Affects Osmium Redox Polymer Synthesis for Wired Enzymatic Biosensors.

微量氧气影响有线酶生物传感器的锇氧化还原聚合物合成。

DOI：
10.1149/1945-7111/ac42a0
发表时间：
2022
期刊：
Journal of the Electrochemical Society
影响因子：
3.9
作者：
Calhoun,MargaretC;Stachurski,ChristopherD;Winn,SaraL;Gizzie,EvanA;Daniel,AaronW;Schley,NathanD;Cliffel,DavidE
通讯作者：
Cliffel,DavidE

Chlorpyrifos Disrupts Acetylcholine Metabolism Across Model Blood-Brain Barrier.