Surface‐Acoustic‐Wave‐Based Lab‐on‐Chip for Rapid Transport of Cryoprotectants across Cell Membrane for Cryopreservation with Significantly Improved Cell Viability

: Cryopreservation is essential to effectively extend the shelf life of delicate biomaterials while maintaining proper levels of cell functions. Cryopreservation requires a cryoprotective agent (CPA) to suppress intracellular ice formation during freezing, but it must be removed prior to clinical use due to its toxicity. Conventional multistep CPA loading and unloading approaches are time consuming, often creating osmotic shocks and causing mechanical injuries for biological samples. An efficient surface-acoustic-wave- (SAW-) based lab-on-a-chip (LoC) for fast loading and removal of CPAs is presented here. With the SAW-based multistep CPA loading/removal approach, high concentration (3 m) CPA can be successfully loaded and removed in less than 1 min. Results show that the technique causes the least harm to umbilical cord matrix mesenchymal stem cells as compared to conventional method, and an average of 24% higher cell recovery rate is achieved, while preserving the integrity and morphology of the cells. This device is the first of its kind to combine high loading/unloading efficiency, high cell viability, and high throughput into one LoC device, offering not only a more efficient and safer route for CPA loading and removal from cells, but also paving the way for other cryopreservation-dependent applications.