OvaReady: An automated microfluidic oocyte retrieval and denudation device expanding access to IVF

OvaReady：一种自动化微流体卵母细胞取出和剥脱装置，扩大 IVF 的使用范围

• 批准号: 10324678
• 负责人: Ismail Emre Ozkumur
• 金额: $ 25.54万
• 依托单位: AUTOIVF, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10324678
• 关键词: Address; Adoption; Age; Area; Aspirate substance; Automobile Driving; Blood Cells; Cattle; Clinic; Collection; Complex; Computer software; Couples; Cryopreservation; Developed Countries; Development; Devices; Embryology; Environment; Equipment; Exposure to; Fertilization; Fertilization in Vitro; Follicular Fluid; Freezing; Germ Cells; Goals; Growth; Health Services Accessibility; Human; Human Resources; Hyaluronidase; Injections; Insemination; Institutional Review Boards; Intracytoplasmic Sperm Injections; Laboratories; Liquid substance; Methods; Microfluidic Microchips; Microfluidics; Molds; Mus; Oocytes; Patients; Performance; Phase; Population Density; Preparation; Production; Recipe; Rest; Safety; Sampling; Small Business Innovation Research Grant; System; Techniques; Technology; Temperature; Touch sensation; Training; United States; Woman; Work; coronavirus disease; cost; design; egg; fertility preservation; geographic inaccessibility; improved; infertility treatment; innovation; manufacturing scale-up; microfluidic technology; novel; oocyte retrieval; pregnant; preservation; procedure cost; process optimization; prototype; scale up; success

In the United States, the total number of In-vitro Fertilization (IVF) clinics has stayed relatively stagnant through the past decade, and the IVF-cycles per million women remains significantly lower than in other developed countries. The greatest challenge for widespread use of IVF include its high cost, driven by the need for complex and expensively equipped IVF laboratories and highly-trained embryologists. An IVF laboratory costs approximately $2 million to build, which has the effect of confining IVF laboratories to high-density population areas, causing geographic inaccessibility. The high cost and accessibility of IVF treatment is the leading reason why couples are unable to undergo and/or delay IVF treatment. Additionally, demand for fertility preservation through egg banking is rapidly increasing, but again the requirement of conducting the egg collection in fully equipped facilities and cost stand as significant hurdles to broader adoption. Our goal is to automate various functions within an embryology lab to decrease the cost and improve the overall accessibility of IVF and egg banking. This will be achieved by reducing the equipment and personnel requirements so as to pave the way towards de-centralization of IVF. Our technology will facilitate processing of gametes at basic satellite clinics prior to them being transferred to central embryology laboratories or long-term storage facilities. We propose to develop and commercialize a novel technique for preparation of human oocytes towards preservation or assisted fertilization, to address both the accessibility and cost limitations. OvaReady, an automated system that will utilize microfluidic devices to collect Cumulus-Oocyte-Complexes (COCs) from follicular fluid aspirate (FFA) and denude them, will enable a one-touch preparation of vitrification or ICSI-ready eggs. OvaReady will utilize innovative microfluidic technology with hardware and software controls, to enable automated isolation of oocytes from FFA. Performing egg denudation in a closed and integrated system will limit exposure of the eggs to deviations in temperature and pH, therefore improving safety, reliability, and efficiency of the IVF treatment by removing inter-/intra-operator variability. A further benefit, more applicable to today’s COVID environment, is that it will limit the operator exposure to potentially harmful agents in FFA. In our preliminary study, we demonstrate a proof of principle microfluidic platform that conducts rapid denudation of mouse oocytes from the COC, while maintaining their viability. In the proposed work, we will build on this innovation and integrate the following functions: COC collection from follicular fluid aspirate; denudation, washing, concentration of eggs to an appropriate handling volume for freezing, transport or insemination. Through this Fast-Track application, we propose and plan to complete the following aims in this order: Develop COC isolation unit and integrate with denudation unit; develop rest of the microfluidic design and generate recipe for reliable egg preparation; transfer microfluidic design to scaled-up manufacturing to achieve reliable performance; demonstrate success of the automated workflow with preparation of human oocytes.

在美国，试管受精(IVF)诊所的总数一直处于相对停滞的状态。 在过去的十年中，每百万妇女的试管受精周期数仍然显著低于其他发达国家 国家。广泛使用试管受精的最大挑战包括其高昂的成本，这是由复杂的 以及昂贵的试管受精实验室和训练有素的胚胎学家。试管受精实验室的费用 大约200万美元的建设资金，其效果是将试管受精实验室限制在高密度人口 区域，造成地理上无法进入。试管受精治疗的高成本和可获得性是领先的 夫妇无法接受和/或推迟试管受精治疗的原因。此外，对生育率的需求 通过鸡蛋银行进行保存的情况正在迅速增加，但再次要求进行鸡蛋 在设备齐全的设施中进行收集和成本是更广泛采用的重大障碍。我们的目标是 自动化胚胎学实验室内的各种功能，以降低成本并提高总体可访问性 试管受精和卵子银行。这将通过减少设备和人员需求来实现，以便 为去中心化试管受精铺平道路。我们的技术将促进配子的基本加工 在将卫星诊所转移到中央胚胎学实验室或长期储存设施之前。 我们建议开发一种新的人类卵母细胞制备技术并将其商业化 保存或辅助受精，以解决可获得性和成本限制。OvaReady，一个 一种自动化系统，将利用微流控设备从 抽吸卵泡液(FFA)并剥离它们，将实现玻璃化或一触式准备 准备好胚胎移植的卵子。OvaReady将利用创新的微流控技术进行硬件和软件控制， 以实现卵母细胞与FFA的自动分离。在封闭的集成系统中进行鸡蛋剥离 将限制鸡蛋暴露在温度和pH的偏差中，从而提高安全性、可靠性和 通过消除操作员间/操作员内的变异性来提高试管受精治疗的效率。另一个好处，更适用于 今天的COVID环境，是它将限制运营商接触FFA中的潜在有害物质。 在我们的初步研究中，我们证明了进行快速剥离的微流控平台的原理 从COC中分离出小鼠卵母细胞，同时保持其活力。在拟议的工作中，我们将以此为基础 创新并集成了以下功能：从卵泡液中收集COC；剥离， 清洗、浓缩卵子至适当的处理量，以供冷冻、运输或授精。 通过这个Fast-Track应用，我们建议并计划按顺序完成以下目标：开发 COC分离单元并与剥离单元集成；开发其余的微流控设计并生成配方 用于可靠的鸡蛋制备；将微流控设计转移到大规模制造中，以实现可靠的 性能；展示自动化工作流程在制备人类卵母细胞方面的成功。