R44HD111134

Ovasafe: A microfluidic device enabling automated oocyte vitrification - Abstract

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 includes its high cost, driven by the need for complex and expensively equipped IVF laboratories and highly-trained embryologists.

The high cost and accessibility of IVF clinics is the leading reason why couples are unable to undergo or delay IVF treatment and/or egg banking. Our company’s goal is to automate various functions within an embryology lab to decrease the cost and improve the overall accessibility of IVF treatments and fertility preservation. We are aiming to achieve this by reducing the equipment and personnel requirements so as to pave the way towards de-centralization of IVF.

Towards this goal, our proposed new technology “Ovasafe” will facilitate vitrification of oocytes prior to them being transferred to central embryology labs for fertilization or long-term storage facilities for preservation. Ovasafe will complement the ongoing project, Ovaready, which automatically prepares oocytes for vitrification.

Ovasafe will utilize microfluidic devices to load cryoprotectant agents (CPA) rapidly and gradually to oocytes, and automatically transfer the oocytes into silica capillary carriers prior to them being plunged into liquid nitrogen to complete the vitrification process.

In addition to improving the accessibility by enabling processing of gametes at satellite clinics, performing gradual CPA loading using microfluidic devices will reduce the CPA exposure, toxicity, and osmotic stress to oocytes. Automated CPA loading and utilization of a closed vitrification carrier will eliminate variations between operators and clinics.

Although the scope of this proposal is limited to oocyte vitrification, the technology can also be applicable to embryo vitrification in the future. In our preliminary studies, we demonstrated that gradual CPA loading using microfluidics and silica capillary vitrification are both practical methods which can improve vitrification outcomes.

We showed that gradual CPA loading decreases the total CPA exposure to oocytes, and reduces the osmotic stress driven by cell shrinkage which is a response to standard step-wise CPA loading protocols. We also demonstrated that silica capillaries can achieve ultra-rapid cooling and warming rates that are comparable to standard open carrier methods, and the vitrification outcomes with silica capillaries are comparable or superior to standard methods.

In the proposed work, we will build on these innovations and integrate both methods in a simple, reliable, and closed system to automate the oocyte vitrification process.

Through this fast-track application, we propose and plan to complete the following aims in this order:

1. Develop a microfluidic CPA loading device;
2. Modify CPA loading device for automated oocyte loading to silica capillaries;
3. Have plastic microfluidic devices and customized silica capillaries manufactured to improve usability;
4. Design and build an automated control system;
5. Demonstrate success of the automated workflow with vitrification of mouse and donated human oocytes.

Autoivf

TO CONDUCT AND SUPPORT LABORATORY RESEARCH, CLINICAL TRIALS, AND STUDIES WITH PEOPLE THAT EXPLORE HEALTH PROCESSES. NICHD RESEARCHERS EXAMINE GROWTH AND DEVELOPMENT, BIOLOGIC AND REPRODUCTIVE FUNCTIONS, BEHAVIOR PATTERNS, AND POPULATION DYNAMICS TO PROTECT AND MAINTAIN THE HEALTH OF ALL PEOPLE. TO EXAMINE THE IMPACT OF DISABILITIES, DISEASES, AND DEFECTS ON THE LIVES OF INDIVIDUALS. WITH THIS INFORMATION, THE NICHD HOPES TO RESTORE, INCREASE, AND MAXIMIZE THE CAPABILITIES OF PEOPLE AFFECTED BY DISEASE AND INJURY. TO SPONSOR TRAINING PROGRAMS FOR SCIENTISTS, DOCTORS, AND RESEARCHERS TO ENSURE THAT NICHD RESEARCH CAN CONTINUE. BY TRAINING THESE PROFESSIONALS IN THE LATEST RESEARCH METHODS AND TECHNOLOGIES, THE NICHD WILL BE ABLE TO CONDUCT ITS RESEARCH AND MAKE HEALTH RESEARCH PROGRESS UNTIL ALL CHILDREN, ADULTS, FAMILIES, AND POPULATIONS ENJOY GOOD HEALTH. THE MISSION OF THE NICHD IS TO ENSURE THAT EVERY PERSON IS BORN HEALTHY AND WANTED, THAT WOMEN SUFFER NO HARMFUL EFFECTS FROM REPRODUCTIVE PROCESSES, AND THAT ALL CHILDREN HAVE THE CHANCE TO ACHIEVE THEIR FULL POTENTIAL FOR HEALTHY AND PRODUCTIVE LIVES, FREE FROM DISEASE OR DISABILITY, AND TO ENSURE THE HEALTH, PRODUCTIVITY, INDEPENDENCE, AND WELL-BEING OF ALL PEOPLE THROUGH OPTIMAL REHABILITATION.

93.865 - Child Health and Human Development Extramural Research

National Institute of Child Health and Human Development (NICHD) [HHS - NIH]

Massachusetts United States

State-Wide

PHS 2021-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) (PA-21-259)

Amendment Since initial award the total obligations have increased 719% from $287,875 to $2,356,535.