title: Microfluidics for cryopreservation.
abstract: Minimizing cell damage throughout the cryopreservation process is critical to enhance the overall outcome. Osmotic shock sustained during the loading and unloading of cryoprotectants (CPAs) is a major source of cell damage during the cryopreservation process. We introduce a microfluidic approach to minimize osmotic shock to cells during cryopreservation. This approach allows us to control the loading and unloading of CPAs in microfluidic channels using diffusion and laminar flow. We provide a theoretical explanation of how the microfluidic approach minimizes osmotic shock in comparison to conventional cryopreservation protocols via cell membrane transport modeling. Finally, we show that biological experiments are consistent with the proposed mathematical model. The results indicate that our novel microfluidic-based approach improves post-thaw cell survivability by up to 25% on average over conventional cryopreservation protocols. The method developed in this study provides a platform to cryopreserve cells with higher viability, functionality, and minimal inter-technician variability. This method introduces microfluidic technologies to the field of biopreservation, opening the door to future advancements at the interface of these fields.
authors.affiliation: Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Bioengineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Young S
authors.initials: YS
authors.lastname: Song
authors.forename: Sangjun
authors.initials: S
authors.lastname: Moon
authors.forename: Leon
authors.initials: L
authors.lastname: Hulli
authors.forename: Syed K
authors.initials: SK
authors.lastname: Hasan
authors.forename: Emre
authors.initials: E
authors.lastname: Kayaalp
authors.forename: Utkan
authors.initials: U
authors.lastname: Demirci
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002470:Cell Survival; D015925:Cryopreservation / Q000295:instrumentation* / Q000379:methods*; D003451:Cryoprotective Agents / Q000493:pharmacokinetics*; D004867:Equipment Design; D006801:Humans; D008099:Liver / Q000166:cytology; D008113:Liver Neoplasms / Q000378:metabolism; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D008954:Models, Biological; D009997:Osmotic Pressure; D012212:Rheology
chemical_list: D003451:Cryoprotective Agents