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.
Public Health Relevance Statement: Demand for fertility treatment and fertility preservation through egg banking is on the rise because of the increasing age that women are seeking to become pregnant but access to these treatments is limited as a result of high costs. Today's laboratories use decades old methods for preparation and preservation of gametes while adding substantial procedural costs and both the in-vitro fertilization and egg banking markets need automated solutions to achieve the high potential growth. We will develop and commercialize a novel microfluidic device, OvaReady, for automated collection and denudation of oocytes, thus enabling a one-touch preparation of vitrification or ICSI-ready eggs, in order to improve the accessibility and reliability of these treatments.
Project Terms: Adoption; Age; ages; Automobile Driving; driving; Blood Cells; Peripheral Blood Cell; Cattle; Bovine Species; bovid; bovine; cow; Couples; Cryopreservation; Cryofixation; cold preservation; cold storage; Embryology; Environment; Equipment; Fertilization; Fertility/Fertilization; Fertilization in Vitro; Test-Tube Fertilization; Follicular Fluid; Liquor Folliculi; Ovarian Follicle Antral Fluid; Freezing; Germ Cells; Gametes; Germ-Line Cells; Reproductive Cells; Sex Cell; initial cell; sexual cell; Goals; Growth; Generalized Growth; Tissue Growth; ontogeny; Health Services Accessibility; Access to Care; access to health services; access to services; access to treatment; accessibility to health services; availability of services; care access; health service access; health services availability; service availability; treatment access; Human; Modern Man; Hyaluronidase; Duran-Reynals Permeability Factor; GL Enzyme; Hyaglosidase; Hyaluronate 4-glycanohydrolase; Hyaluronate Hydrolase; Hyaluronoglucosaminidase; Insemination; Laboratories; Methods; Mus; Mice; Mice Mammals; Murine; Oocytes; Ovocytes; Patients; Population Density; Production; Rest; Safety; Computer software; Software; Technology; Temperature; United States; Woman; Work; improved; Area; Phase; Training; Developed Countries; Industrialized Countries; Industrialized Nations; developed country; developed nation; developed nations; fluid; liquid; Liquid substance; Exposure to; Filamentous Fungi; Molds; Aspirate; Aspirate substance; Complex; Clinic; Techniques; System; ICSI; Intracytoplasmic Sperm Injections; Performance; success; Recipe; novel; Devices; Manpower; personnel; Human Resources; Touch; tactile sensation; Touch sensation; Sampling; µfluidic; Microfluidics; Address; Microfluidic Device; Microfluidic Lab-On-A-Chip; microfluidic chip; Microfluidic Microchips; Collection; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Preparation; Development; developmental; cost; design; designing; scale up; innovation; innovate; innovative; egg; prototype; pregnant; process optimization; manufacturing scale-up; Institutional Review Boards; IRB; IRBs; infertility treatment; fertility assistance; fertility interventions; fertility treatment; geographic inaccessibility; Injections; procedure cost; procedural costs; preservation; microfluidic technology; µfluidic technology; fertility preservation; preserve fertility; oocyte retrieval; egg retrieval; coronavirus disease; COVID; CoV disease; corona virus disease
