Our lab has pioneered the use of two FDA-approved nanoparticle platforms—iron oxide and gold nanoparticles—to rewarm cryopreserved biomaterials using radiofrequency and laser irradiation, respectively. Using silica-coated iron oxide nanoparticles (sIONPs), we have demonstrated the successful cryopreservation and rewarming of a mammalian kidney that supported robust transplantation following cryopreservation [Han and Rao et al.]. This approach involves perfusing the nanoparticles throughout the organ vasculature, enabling radiofrequency (alternating magnetic field) heating from within the tissue. By achieving rapid and spatially uniform internal warming, this approach minimizes ice recrystallization and thermal stress, two major failure modes associated with conventional convective rewarming of large vitrified tissues and organs.
At smaller scales, we have similarly demonstrated plasmonic rewarming using laser-heated gold nanoparticles in a range of living systems, including zebrafish embryos, coral larvae, and mammalian cells. By generating heat internally through plasmonic nanoparticles, this approach enables faster warming rates while reducing the concentration of cryoprotective agents required for successful cryopreservation and rewarming.
These and other cryopreservation technologies are being translated toward commercialization through member partners of the NSF Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio), which our lab directs.
Publications
Selected publications using RF nanowarming with iron oxide:
Etheridge ML, Xu Y, Rott L, Choi J, Glasmacher B, and Bischof JC. Radiofrequency Heating of Magnetic Nanoparticles Improves the Thawing of Cryopreserved Biomaterials. Technology. 2014;2(3):229-42. (First demonstration of volumetric heating in frozen and vitrified systems using RF heating of iron oxide).
Manuchehrabadi N, Gao Z, Zhang J, Ring HL, Shao Q, Liu F, McDermott M, Fok A, Rabin Y, Brockbank KG, Garwood M and Bischof JC. Improved tissue cryopreservation using inductive heating of magnetic nanoparticles. Sci Trans Med. 2017;9(379): p.eaah4586. (Cover Article – first successful and scalable volumetric rewarming of tissues)
Manuchehrabadi N, Shi M, Roy P, Han Z, Qiu J, Xu F, Lu TJ, Bischof JC. Ultrarapid Inductive Rewarming of Vitrified Biomaterials with Thin Metal Forms. Ann Biomed Eng. 2018;46(11):1857-1869. (First demonstration that RF can inductively heat metals and iron oxide nanoparticles for improved cryopreservation. Athanasiou Best Paper Award BMES 2019)
Han Z, Rao JS, Ramesh S, Gangwar L, Namsrai BE, Pasek-Allen, JL, Etheridge ML, Wolf, SM, Pruett, TL, Finger EB, Bischof JC. Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model. Nature Commun. 2023;14:3407. (First robust cryopreservation of a mammalian organ that when transplanted solely supported the life of the recipient. Featured on Cover of Science 6/23)
Gangwar L, Han Z, Scheithauer C, Namsrai BE, Kantesaria S, Goldstein R, Etheridge ML, Finger EB, Bischof JC. Physical vitrification and nanowarming at liter-scale CPA volumes: toward organ cryopreservation. Nature Communications. 2025;16(1):8511. (Demonstration of vitrification and nanowarming at the scale of human organs. Inaugural Cravalho Cryobiology Engineering Paper Award 2026)
Gao Z, Namsrai B, Han Z, Joshi P, Rao JS, Ravikumar V, Sharma A, Ring HL, Idiyatullin D, Magnuson E…Bischof JC. Vitrification and Rewarming of Magnetic Nanoparticle-Loaded Rat Hearts. Adv Mater Technol. 2022;7(3):2100873. (Demonstration of nanowarming in rat hearts)
Sharma A, Lee CY, Namsrai BE, Han Z…Bischof JC, Finger EB. Cryopreservation of Whole Rat Livers by Vitrification and Nanowarming. [published correction appears in Ann Biomed Eng. 2022 Nov 29]. Ann Biomed Eng. 2023;51(3):566-577. (Demonstration of nanowarming in rat livers)
Selected articles using laser gold nanowarming approach:
Qin Z, Bischof JC. Thermophysical and Biological Responses of Gold Nanoparticle Laser Heating. Chem Soc Reviews. 2012;41:1191-217. (Invited and highly cited review of laser nanoparticle heating for application in cryopreservation and other nanomedicine applications).
Liu Y , Kangas J, Wang Y, Khosla K, Pasek-Allen J, Zhan, L., Saunders A, Oldenburg S, Bischof JC. Photothermal conversion of gold nanoparticles for uniform pulsed laser warming of vitrified biomaterials. Nanoscale. 2020 Jun 21;12(23):12346-12356. Epub 2020 Jun 3. Erratum in: Nanoscale. 2020 Oct 15;12(39):20543. (Modeling work to improve the matching of the laser to the size and albedo – scattering and absorption – in the droplet)
Khosla K, Wang Y, Hagedorn M, Qin Z and Bischof JC. "Gold Nanorod Induced Warming of Embryos from the Cryogenic State Enhances Viability." ACS Nano. 2017;11(8):7869–7878. (First successful teleost fish embryo cryopreservation. Source of new R24 grant to cryopreserve mitochondrial mutations in Zebrafish)
Khosla K, Kangas J, Liu Y, Zhan L, Daly J, Hagedorn M, Bischof JC. Cryopreservation and Laser Nanowarming of Zebrafish Embryos Followed by Hatching and Spawning. Adv Biosyst. 2020 Nov;4(11):e2000138. (First demonstration that laser nanowarmed embryos grow to adulthood and breed normally).
Zhan L, Guo SZ, Kangas J, Shao Q, Shiao M, Khosla K, Low WC, McAlpine MC, Bischof JC. Conduction cooling and plasmonic heating dramatically increase droplet vitrification volumes for cell cryopreservation. Advanced Science 2021:8(19);2004605.(Shows ability to use droplet “splat” cooling on LN2 cooled copper followed by laser nanowarming to reduce CPA and increase droplet sizes for increased throughput)
Daly J, Zuchowicz N, Nuñez Lendo CI, Khosla K, Lager C, Henley EM, Bischof JC, Kleinhans FW, Lin C, Peters EC, Hagedorn M. Successful cryopreservation of coral larvae using vitrification and laser warming. Sci Rep. 2018 Oct 24;8(1):15714. (First demonstration of coral larvae cryopreservation and rewarming using laser nanowarming).
Daly J, Bouwmeester J, Perry R, Page C, Khosla K, Kangas J, Lager C, Hardy K, Bischof JC, Hagedorn M. The first proof of concept demonstration of nanowarming in coral tissue. Sustainable Systems 7.10 (2023): 2300303. (First demonstration that coral polyps can be cryopreserved and rewarmed by laser nanowarming thereby obviating the need to wait for embryos during infrequent spawning events).