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: 10613599
• 负责人: Ismail Emre Ozkumur
• 金额: $ 81.54万
• 依托单位: AUTOIVF, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10613599
• 关键词: Address; Adoption; Age; Area; Automobile Driving; Blood Cells; Cattle; Clinic; Collection; Complex; Computer software; Couples; Cryopreservation; Decentralization; 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; Marketing; Methods; Microfluidic Microchips; Microfluidics; Molds; Mus; Oocytes; Patients; Performance; Phase; Population Density; Preparation; Production; Recipe; Rest; Safety; Sampling; Small Business Innovation Research Grant; System; Systems Integration; Techniques; Technology; Temperature; Training; United States; Woman; Work; access restrictions; aspirate; commercialization; coronavirus disease; cost; design; egg; fertility preservation; geographic inaccessibility; improved; infertility treatment; innovation; manufacturing scale-up; microfluidic technology; novel; oocyte retrieval; parallelization; pregnant; preservation; procedure cost; process optimization; prototype; 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，体外受精（IVF）诊所的总数一直相对停滞， 在过去十年中，每百万妇女的IVF周期仍然明显低于其他发达国家， 国家试管婴儿广泛使用的最大挑战包括其高成本，这是由复杂的 设备昂贵的试管婴儿实验室和训练有素的胚胎学家。IVF实验室费用 大约200万美元的建设，这有限制试管婴儿实验室的高密度人口的影响 造成地理上的不便。试管婴儿治疗的高成本和可及性是领先的 夫妇无法接受和/或延迟IVF治疗的原因。此外，生育需求 通过卵子银行进行保存的需求正在迅速增加， 设备齐全的设施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，以降低成本并提高整体可访问性 试管婴儿和卵子银行这将通过减少设备和人员需求来实现， 为IVF的去中心化铺平道路。我们的技术将促进配子的处理， 在转移到中央胚胎学实验室或长期储存设施之前，必须先在卫星诊所进行检查。 我们建议开发和商业化一种新的技术，用于制备人类卵母细胞， 保存或辅助受精，以解决可及性和成本限制。OvaReady， 自动化系统，将利用微流体装置收集卵丘卵母细胞复合物（COCs）， 卵泡液抽吸物（FFA）并剥脱它们，将使玻璃化或冷冻的一触式准备成为可能。 ICSI准备好的鸡蛋OvaReady将利用创新的微流控技术与硬件和软件控制， 以实现从FFA自动分离卵母细胞。在一个封闭的综合系统中进行剥卵 将限制鸡蛋暴露于温度和pH值的偏差，从而提高安全性，可靠性， 通过消除操作者间/操作者内的差异来提高IVF治疗的效率。另一个好处，更适用于 在今天的COVID环境中，它将限制操作员暴露于FFA中的潜在有害因子。 在我们的初步研究中，我们展示了一种原理性的微流体平台， 从COC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：从卵泡液吸出物中收集COC;剥脱， 清洗、浓缩卵子至适当的处理体积，以便冷冻、运输或授精。 通过这个快速通道申请，我们提出并计划按以下顺序完成以下目标： COC分离单元并与剥蚀单元集成;开发其余的微流体设计并生成配方 用于可靠的鸡蛋制备;将微流体设计转移到大规模制造中， 性能;证明制备人卵母细胞的自动化工作流程的成功。