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) 诊所的总数一直保持相对停滞状态 过去十年，每百万妇女的试管受精周期仍显着低于其他发达国家 广泛使用体外受精的最大挑战包括由于复杂的需求而导致的高成本。 以及设备昂贵的体外受精实验室和训练有素的胚胎学家。 耗资约 200 万美元建造，其效果是将 IVF 实验室限制在高密度人群中 地区，导致 IVF 治疗的高成本和可及性是主要的。 此外，夫妇无法接受和/或推迟体外受精治疗的原因还在于对生育的需求。 通过卵子银行保存的情况正在迅速增加，但对卵子进行保存的要求再次提高 在设备齐全的设施中收集和成本是更广泛采用的重大障碍。 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 这将通过减少设备和人员需求来实现。 为体外受精的分散化铺平道路，我们的技术将从根本上促进配子的处理。 卫星诊所，然后再转移到中央胚胎学实验室或长期储存设施。 我们建议开发并商业化一种制备人类卵母细胞的新技术 保存或辅助受精，以解决可及性和成本限制。 自动化系统将利用微流体装置收集卵丘卵母细胞复合物（COC） 卵泡液抽吸（FFA）并剥去它们，将能够一键式准备玻璃化或 OvaReady 将利用创新的微流体技术以及硬件和控制软件， 能够在封闭的集成系统中自动从 FFA 中分离卵母细胞。 将限制鸡蛋暴露于温度和 pH 值偏差的情况，从而提高安全性、可靠性和 通过消除操作者之间/内部的差异来提高体外受精治疗的效率另一个好处是，更适用于。 在当今的新冠病毒环境中，它将限制操作员接触 FFA 中的潜在有害物质。 在我们的初步研究中，我们展示了一种可进行快速剥蚀的原理证明微流体平台 在拟议的工作中，我们将以此为基础。 创新并集成以下功能：从卵泡液抽吸中收集COC； 清洗、将卵子浓缩至适当的处理体积以进行冷冻、运输或授精。 通过此快速通道应用程序，我们建议并计划按顺序完成以下目标： COC 分离单元并与剥脱单元集成；开发微流体设计的其余部分并生成配方 用于可靠的鸡蛋制备；将微流体设计转移到规模化制造以实现可靠的 性能；展示人类卵母细胞制备自动化工作流程的成功。