Microfluidic Embryo Culture and Analysis

微流控胚胎培养和分析

基本信息

批准号：
7038279
负责人：
SHUICHI TAKAYAMA
金额：
$ 16.04万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2008-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7038279
关键词：
bioengineering /biomedical engineering biomarker biomedical equipment development biomimetics bioreactors biotechnology embryo /fetus culture embryogenic cleavage in vitro fertilization insulinlike growth factor laboratory mouse lactates mammalian embryology microfluidics

项目摘要

DESCRIPTION (provided by applicant): This proposal is a design-directed project to develop a novel microfluidic bioreactor that will culture multiple single embryos under simulated physiological conditions while simultaneously performing real-time monitoring of biochemical markers of embryo quality. Reducing the incidence of high-order multiple pregnancies while maintaining the overall IVF success Irate is a holy grail of human IVF and would be greatly assisted by the ability to produce and identify the highest quality embryos. This goal has been elusive to date due, at least in part, to the lack of instrumentation to perform convenient and reliable single embryo manipulation and analysis. Because of the small quantities of biomarkers produced by single embryos, reliable quantification hinges on the ability to culture the embryos in very small volumes of fluid and to directly analyze the culture media for soluble biomarkers secreted by embryos with minimal dilution. The proposed microbioreactor with microfluidic pumps, valves, and sensors will provide an inherently biomimetic milieu for embryo culture as well as enable direct biomarker analysis on chip. The microbioreactor will utilize a computer-controlled integrated microfluidics platform that controls fluid flow inside elastomeric capillaries by deformation of the microchannels with mechanical microactuators. The biomarkers of mouse embryo health that will be monitored in this exploratory grant are embryo metabolites, autocrine factors, and embryo surface biomarker of embryo health. The embryo microbioreactor will be used to specifically test the hypothesis that analysis of select biochemical markers will enable prediction of which 8 cell embryo will proceed to produce healthy blastocysts. This test will mainly serve the purpose of device validation and concept feasibility but it also has clinical relevance. A current trend is to grow embryos to the blastocyst stage and transfer the two morphologically "best" blastocyst. Recently, however, two reports using mouse embryos have independently demonstrated that extended culture to the blastocyst stage causes aberrant genetic imprinting and altered postnatal development, growth, physiology and behavior. Case reports and studies also suggest a general association between in vitro culture to the blastocyst stage and MZ twinning. This proposal will address these issues by developing novel non-invasive means of selecting embryos with the greatest implantation potential, with the least amount of manipulation and culture.

描述（由申请人提供）：该提案是一个以设计为导向的项目，旨在开发一种新型的微流体生物反应器，该项目将在模拟生理条件下培养多个单个胚胎，同时对胚胎质量的生化标记进行实时监测。减少高级多重妊娠的发生率，同时保持整体IVF成功是人类IVF的圣杯，并且能够在产生和识别最高质量的胚胎的能力方面得到极大的帮助。至少部分是由于缺乏仪器来执行方便且可靠的单个胚胎操纵和分析的仪器，因此难以捉摸。由于单个胚胎产生的少量生物标志物，可靠的定量铰链取决于培养胚胎以很少的液体培养胚胎的能力，并直接分析培养培养基，以最少稀释而被胚胎分泌的可溶性生物标志物。提出的带有微流体泵，阀门和传感器的微生物反应器将为胚胎培养物固有的仿生环境提供，并在芯片上启用直接的生物标志物分析。微生物反应器将利用计算机控制的集成微流体平台，该平台通过用机械微校准器的微通道的变形来控制弹性毛细管内部的流体流。将在此探索性赠款中监测的小鼠胚胎健康的生物标志物是胚胎代谢物，自分泌因素和胚胎健康的胚胎表面生物标志物。胚胎微生物反应器将用于特异性测试以下假设：对精选生化标记的分析将启用8个细胞胚胎的预测，以产生健康的胚泡。该测试将主要达到设备验证和概念可行性的目的，但也具有临床意义。当前的趋势是将胚胎生长到胚泡阶段，并在形态上“最佳”胚泡传递两个。然而，最近，两份使用小鼠胚胎的报道独立地证明，胚泡阶段的扩展培养物会引起异常的遗传印记并改变了产后发育，生长，生理学和行为。病例报告和研究还表明，体外培养与胚泡阶段与MZ孪生之间存在一般关联。该建议将通过开发具有最大植入潜力的胚胎的新型非侵入性手段来解决这些问题，而操纵和文化的数量最少。