Liquid Exchange and Positioning of Cellular Entities in a Liquid-air Interface

This technology is a hanging drop-based microfluidic system, device, and method for liquid exchange in the vitrification of an egg or embryo. The method involves forming a hanging drop chamber, receiving the specimen into the chamber, and loading various liquids into the plurality of microfluidic channels to facilitate a controlled liquid exchange surrounding the cell prior to freezing. By automating the delicate process of cryoprotectant loading and specimen retrieval, this technology ensures low-cost, scalable, and consistent outcomes.

Researchers

Linda Griffith / Georgios Katsikis / Haidong Feng / Joseph Doyle / Scott Manalis

Departments: Department of Biological Engineering
Technology Areas: Biotechnology: Biomedical Devices & Systems

  • liquid exchange and positioning of cellular entities in a liquid-air interface
    Patent Cooperation Treaty | Pending

Technology 

An egg or embryo is first loaded into the disposable chamber (or hanging drop). From there, it sinks due to gravity and migrates towards the liquid-air interface of the chamber, which has an opening connected to the microfluidic channel in the housing. Once in the housing, the liquid exchange process commences by flowing different liquids (e.g., cryoprotectants) through the inlet and microfluidic channel and out through outlet. Once the specimen has been retrieved from the chamber via a vitrification carrier (such as a cryoloop which can be connected to a robotic arm), it is rapidly moved into a vitrification medium, such as liquid nitrogen, to complete the freezing process for long term storage.  

Problem Addressed 

The absence of an automated method for egg or embryo freezing has caused the egg vitrification market to have high costs, low scalability, and high variability in clinical outcomes. Egg freezing’s technical and sensitive nature necessitates highly trained embryologists, which are in limited supply. However, even with skilled embryologists, damage to eggs can still occur during several critical steps of vitrification, namely loading of the cryoprotectant, timing of the processes, and using too much liquid during freezing. An automated device operated by an entry-level embryologist could ensure consistent clinical outcomes comparable to top-tier experts and enable scalability. By significantly reducing the level of technical skill and clinical infrastructure needed to perform reliable egg freezing, this invention can simultaneously improve the quality of cryopreservation, lower costs, increase the number of viable cells upon thawing, and enable expanded access for patients.  

Advantages 

  • Reduces the level of technical skill and clinical infrastructure needed for egg or embryo freezing

  • Provides a fully automated and self-contained system for vitrification

  • Can be fully operated by entry-level technicians

  • Decreased likelihood of damaging eggs

  • Improved reliability and quality of cryopreservation 

Publications

Haidong, F., et al. "A Microfluidic Hanging Droplet as a Programmable Platform for Mammalian Egg Vitrification." Lab on a Chip 24 (2024): 5225–5237. https://doi.org/10.1039/D4LC00428K.

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