Figure 1: CryoMesh workflow for pancreatic-islet vitrification. Islets in cryoprotective-agent solution are transferred to a porous mesh, which removes excess solution before rapid cooling in liquid nitrogen.
Figure 2: Comparison of conventional convection, convection-dominated CryoMesh, and conduction-dominated CryoMesh platforms. Guo et al., Advanced Science (2024).
Our lab helped develop CryoMesh, a scalable platform for the vitrification and rewarming of biological systems. Unlike traditional vitrification devices such as straws and cryoloops, CryoMesh uses a porous mesh to wick away excess cryoprotective agent (CPA) surrounding the biological material. This reduces the thermal mass of the system and enables substantially faster cooling and rewarming while maintaining high-throughput processing. The resulting increase in heat transfer rates also enables the development of lower-CPA protocols, which can reduce CPA toxicity in sensitive biological systems.
CryoMesh has enabled clinically scalable, high-viability, high-functioning cryopreservation of pancreatic islets, allowing donor- and stem cell-derived islets to be pooled and cryopreserved for transplantation, with demonstrated efficacy in both mouse and non-human primate (NHP) models [Zhan & Rao et al.]. The platform has also enabled the first robust cryopreservation of Drosophila embryos, supporting the long-term banking of genetic lines for research laboratories and stock centers [Zhan et al.]. In addition, CryoMesh has been applied to precision-cut liver slices (PCLS), an important model for drug discovery and toxicity testing, enabling the development of an “off-the-shelf” supply of cryopreserved PCLS with metabolic and functional properties comparable to fresh tissue [Ramesh et al.].
We have further developed engineering principles for optimizing CryoMesh for biological systems of different sizes and heat-transfer requirements. Polymer meshes, such as nylon, can promote convection-dominated heat transfer, while high-thermal-conductivity metal meshes, such as copper and stainless steel, can enable conduction-dominated heat transfer. Cooling and rewarming rates can be further enhanced through vertical plunging, which minimizes the Leidenfrost vapor layer that can otherwise limit heat transfer during immersion in liquid nitrogen [Guo et al.]. Optimization of mesh properties—including material, wire diameter, and pore size—allows the thermal response of CryoMesh to be tailored to different biological systems.
Using conductive metal meshes, optimized mesh geometries, and vertical plunging, conduction-dominated CryoMesh platforms can achieve approximately an order-of-magnitude higher cooling and rewarming rates than conventional nylon meshes. These higher rates enable further reductions in CPA concentration, opening new possibilities for the cryopreservation of embryos, organoids, tissues, and other sensitive biological systems. The technology can also be combined with electrically resistive heating, or Joule heating, to further accelerate rewarming and reduce CPA requirements [Zhan et al.].
CryoMesh technology is being commercialized by our startup, NorthStar Cryo.
Publications
Selected publications include:
Zhan L, Li M, Hays T, Bischof JC. Cryopreservation method for Drosophila melanogaster embryos. Nature Communications 2021 April:12;2412. (First robust protocol to cryopreserve Drosophila embryos across multiple lines (25). Led to an NIH R24 grant with the Bloomington Stock Center to preserve both lab and stock center embryos where space has now run out to hold new lines)
Zhan L, Rao JS, Sethia N, Slama MQ, Han Z, Tobolt D, Etheridge M, Peterson QP, Dutcher CS, Bischof JC, Finger EB. Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation. Nature Medicine 2022:28(4);798-808. (First example of high viability, function and yield for pancreatic islets that reverse diabetes in mice.)
Rao, JS, Z Guo, Z Khashim, K Knofczynski, D Tobolt, SB Shivakumar, … Bischof JC, Finger, EB. Clinical-grade cryopreservation unlocks transplant-ready human pancreatic and stem cell–derived islets for diabetes therapy. bioRxiv, 2026.04. 25.720819. (First clinical scaling of cryopreserved islets in Nature Medicine 2022 article to be used to treat diabetic patients in the future).
Zhan L, Han Z, Saho Q, Etheridge M, Hays T, Bischof J. Rapid joule heating improves vitrification based cryopreservation. Nature Comm. 2022;13(1):6017 (Electrification of the mesh increases heating rates and thereby reduces potentially toxic CPAs)
Guo Z, Zuchowicz N, Bouwmeester J, Joshi AS, Neisch AL, Smith K, Daly J, Etheridge ML, Finger EB, Kodandaramaiah SB, Hays TS, Hagedorn M, Bischof JC. Conduction-Dominated Cryomesh for Organism Vitrification. Adv Sci (Weinh). 2024;11(3):e2303317. (This work fully characterizes the mesh material, pore size and liquid nitrogen convective cooling for optimal results).
Ramesh, S.; Rao, J. S.; Namsrai, B.-E.; Fisher, B.; Tobolt, D. K.; Megaly, M.; Etheridge, M. L.; Pruett, T. L.; Seelig, D.; Murugan, P.; Aldaraiseh, B.; Finger, E. B.; Bischof, J. C. Vitrification and Rapid Rewarming of Precision-Cut Liver Slices for Pharmacological and Biomedical Research. Bioengineering & Translational Medicine 2026, 11 (1), e70045. https://doi.org/10.1002/btm2.70045.