Same day embryo viability sensor for high throughput embryo transfer selection

摘要 生物医学研究界广泛依赖于可用性和持续的 利用啮齿动物研究模型。随着CRISPR的发现， 它允许科学家操纵基因组的程度，临床上的爆炸， 相关的模型已经存在。精准医疗的前沿是 负责有害SNP突变的表型分析， 不同种族的人群，以及对孤儿疾病的了解。生产这些 模型严重依赖于体外辅助生殖技术，包括冷冻， 保存，基因编辑和体外受精，然而，这些技术也减少了 胚胎的繁殖能力和活产率。作为唯一的 模型继续增加设施需要自动化和标准化的体外辅助 繁殖工具，以灵活地扩大需求，并保持更大的窝。至胚胎日期 通过口腔移液进行处理，并通过 要么尽快转移所有可用的胚胎，要么等待几个胚胎， 几天后受损的细胞最终停止生长，留下一些有能力的囊胚。最近 发展已经测量了卵母细胞/胚胎作为非侵入性生物- 通过光学测量胚胎变形时， 微量移液器;然而，这种技术仍然需要手动操作， 制度不完善。我们建议建立一个高通量的微流控芯片实验室， 在暴露于环境压力后立即鉴定胚胎的存活能力， 冷冻保存、基因编辑和体外受精。基于已知的 受精卵机械特性的预测能力和Ravata的微电极平台，我们 将验证一个电传感器阵列，以电量化胚胎位移通过 微流控吸引器，用于测量早期胚胎的细胞核和细胞质成熟 活性检测系统

Abstract The biomedical research community extensively relies on the availability and continued utilization of the rodent research model. With the discovery of CRISPR, and the unprecedented degree with which it allowed scientists to manipulate the genome, an explosion of clinically relevant models has made their way into existence. This leading edge of precision medicine is responsible for the phenotyping of harmful SNP mutations, modeling of disease variants in ethnically distinct populations, and understanding of orphan diseases. Production of these models heavily relies upon in-vitro assisted reproductive techniques including cryo- preservation, gene editing, and in-vitro fertilization however these techniques also reduce the reproductive viability of embryos and the percentage of live-born. As the number of unique models continues to increase facilities require automated and standardized in-vitro assisted reproductive tools to flexibly scale with demand and maintain larger litters. To date embryo handling has been done via mouth pipetting, and embryo viability has been assessed through attrition by either transferring all the available embryos as soon as possible or waiting several days for the damaged cells to eventually arrest leaving some competent blastocysts. Recent developments have measured oocyte/embryo mechanical properties as a non-invasive bio- marker of viability by optically measuring embryo deformation when aspirating through a micro-pipette; however, this technique is still manually demanding and measurement collection systems are imperfect. We propose building a high-throughput microfluidic lab on chip that can identify the viability of embryos immediately after exposure to environmental stresses brought on from cryo-preservation, gene editing, and in-vitro fertilization. Building on the known predictive power of zygote mechanical properties and Ravata’s micro-electrode platform, we would validate an electrical sensor array to electrically quantify embryo displacement through a microfluidic aspirator to measure nuclear and cytoplasmic maturation as an early embryo viability detection system.