Instrumenting the Fetal Membrane on a Chip

在芯片上检测胎儿膜

• 批准号: 10037372
• 负责人: DAVID E CLIFFEL
• 金额: $ 66.29万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 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/10037372
• 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; response; sensor; stillbirth

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 胎膜的。涉及胎膜的感染极难治愈 在子宫内进行研究，既因为交通不便，又因为其复杂性 母亲和孩子之间的界面。因此，对妊娠相关病症的研究 受益于胎膜的体外模型，即高度仪器化的胎儿 芯片上的膜（IFMOC）。具体来说，该研究项目的总体目标 是应用多维分析技术和微流控工程设计 定义体外胎膜感染的免疫反应生物特征。 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 该计划的目的是开发一个简单、廉价且强大的片上实验室系统，该系统将 允许在病程早期对感染进行准确的病因学诊断 关于感染的全身宿主反应特征。我们还将利用敏感和 区分急性感染和先前存在的慢性感染的具体方法 感染和/或无症状微生物定植。这项工作将基于 对传染病和意志的人类系统生物学的基本了解 受益于片上器官微流体、光学、电流分析和 酶传感器和质谱分析。我们最初的多分析物传感器配置文件是 专注于利用葡萄糖消耗和乳酸产生的细胞生物能学， 通过我们的微型安培计测量超氧化物产生的氧化爆发 传感器以及石英晶体微天平分泌的 MIC-1 蛋白； 随后，这些特征将通过离子淌度质谱法得到扩展 (IM-MS)。