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 根据病情早期对感染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）。