基于微流控的芯片子宫研究

The existing assisted reproductive technologies have disadvantages of low successful rate and high postnatal risk of fetus.Therefore, the development of high-quality assisted reproductive new technology is urgently required.It is likely that microfluidic will become a new generation of assisted reproduction technology platform solving the above mentioned questions.This study aims to develop an on-chip uterus capable of sperm sorting, fertilization and embryo culture. First, sperm is sorted through simulation of cervical canal using microchannels.Second, based on the characteristics of thermotaxis and chemiotaxis of sperm, the countercurrent swimming sperm will be sorted again in microchannels. After these two stages, fertilization is achieved through combining the selected sperm with oocytes, respectively.Subsequently,fertilized oocytes will be co-cultured in a 3D microenvironment, with oviduct epithelial cells on paper substrate materials, in effort to mimic the fallopian tube in vivo. To simulate the way of substance exchange in uterus, active perfusion in microchannels combined with passive diffusion in paper material can be achieved utilizing the characteristics of material and structure in microfluidic. The embryo-endometrium and interstitium-endometrium interactions in microenvironment can be constructed for embryo development.To validate the feasibility, murine uterus and sperm co-culture on microfluidic will be used as a model, using the methods of step-by-step experiments, comparison validation, function integration and overall performance test for evaluation, eventually the on-chip uterus can be optimized and accomplished. This work is expected to construct a new and highly imitated platform of assisted reproductive technology.

现有的辅助生殖技术存在成功率低和胎儿出生后风险高等问题，因此发展高质量的新技术已成为辅助生殖的迫切要求。然而，微流控芯片有可能成为解决上述问题的新技术平台。本研究拟发展一种基于微流控原理的芯片子宫用于精子分选、受精与胚胎培养。利用微通道模拟子宫颈管对精子进行第一次分选，模拟获能精子的趋温性和趋化性在微通道中逆流泳动对精子进行第二次分选，从而与卵子结合实现受精；利用纸作基质材料在表面进行输卵管内膜细胞和受精卵三维共培养，模拟输卵管中受精卵生长。利用芯片材料和结构的特性结合微通道主动灌流与纸材料中的被动扩散，模拟子宫组织的物质交换形式，构建胚胎-子宫内膜以及子宫内膜-间质相互作用的微环境供胚胎发育。以鼠精子及其子宫为模型体系，采用分步实施、对比验证、功能集成、整体性能比对测试的方式考察芯片系统的前述性能，指导优化并最终实现功能性芯片子宫。本工作有望发展出一种高仿真度的辅助生殖新技术与新平台。

体外受精-胚胎移植（IVF-ET），是辅助生殖技术的重要内容。该技术是指将从母体取出的卵子体外受精并发育成前期胚胎后移植回母体子宫内，经妊娠后分娩婴儿。尽管IVF-ET取得了巨大的成功，该技术仍旧存在许多不足，其中最突出的问题包括妊娠率低、多胎妊娠发生率明显增高和出生后缺陷风险增高。这些问题主要是由于现有细胞培养技术不能有效模拟体内条件，因而影响了胚胎质量。因此，现实医疗工作中迫切需要一种能够模拟子宫环境，保证高质量受精和胚胎发育的细胞培养技术。.微流控芯片是组织、器官仿真的有力工具。前期研究报导了一系列基于微流控芯片的精子分选、受精以及胚胎发育等单元操作技术。在这些工作基础上，有望在微流控芯片上实现子宫整体功能以期改善体外胚胎发育质量。出于上述考虑，本研究设计了一种微流控芯片子宫，保证在类似子宫内部的环境下实现排卵、受精和胚胎发生。初步结果显示，芯片子宫较之传统细胞培养平台可以获得更高的桑椹胚率和囊胚率。