Development of A New Microrobotic System for Cryopreservation of Reproductive Cells

Description

Infertility is a global health problem affecting millions of patients worldwide. According to statistics, the fertility rate in Hong Kong declined from 1,285 to 1,051 live births per thousand women during the period between 2012 and 2019. Infertile couples could be treated by in vitro fertilization to regain their fertility. In clinics, oocytes and fertilized embryos are routinely processed and cryopreserved in liquid nitrogen for future IVF procedures. Vitrification, commonly known as fast freezing, is the most popular cryopreservation method that can achieve improved cell survivability compared to traditional slow freezing. Clinical vitrification requires tedious micromanipulation under the microscope by skilled embryologists to wash oocytes or embryos in cryoprotectant mediums with strict time control.The advancement of microrobotics has offered assistive systems and devices to minimize human involvement and inconsistency. However, existing microrobotic systems require users to teleoperate a robotic manipulator in front of a computer screen and therefore suffer from a low degree of automation. The automated manipulation of reproductive cells for vitrification is largely underexplored because cell size and geometry change significantly due to the osmotic pressure variations in different vitrification mediums, making recognition and control of cells challenging. Aiming to address the limitations of existing solutions and build a fully automated system for vitrification of embryos, we propose to combine electrowetting with microrobotics for high-throughput cell manipulation. The new system will be achieved by innovating the following functions: (1) robust control of cell positioning in a micropipette; (2) learning-based computer vision algorithms for cell recognition to monitor and predict the volume changes; (3) electrowetting on dielectric devices (EWOD) for micromanipulation with droplets; and (4) new design of paper-based vitrification straw for eliminating residual liquid to improve the vitrification success rate and embryo survival rate.In this research, we will apply the new microrobotic system to automatically process the mouse embryos in an equilibrium solution and later transfer them to EWOD devices for processing with individualized time control. The processed embryos inside the vitrification droplet will be moved to the hydrophilic paper straw by the applied electric field. The vitrified embryos on the straw will be frozen in liquid nitrogen. With minimal modifications, the proposed research has a high potential to revolutionize the microrobotic cell manipulation for broader implications. The success of the project would be able to build theoretical and experimental foundations for the next generation of microrobotic systems with minimized human intervention and increased system throughput.