Cryogenics meets Oncology


Cryo-preservation involves the process of cooling cells or whole tissues to sub-zero temperatures at which any biological activity, including the biochemical reactions that would lead to cell death, is effectively stopped. The protocols for biological specimen freezing, termed “snap freezing” or “flash freezing”, are recommended by the National Cancer Institute (NCI), European Organization for Research and Treatment of Cancer and International Society for Biological and Environmental Repositories (ISBER). The most commonly used snap-freezing technique involves immersion of the sample in an ultra-cold bath of quenching fluid such as liquid nitrogen or iso-pentane. A tissue sample is transferred to standard cryo-vials and frozen by immersing the sealed cryo-vial into the iso-pentane bath. Alternatively, liquid nitrogen quenching (- 196 oC) or an iso-pentane bath cooled using dry ice (- 80 oC) may be employed, depending upon the tissue type, specimen size, and availability of resources. Snap-freezing tissues for diagnostic and research purposes are therefore often laborious, even hazardous and not user friendly, and are therefore should not applied at the location of biopsy acquisition.

A portable and user friendly cryogenic environment that enables controlled fast cooling of body tissue without using any of the hazardous coolants and also retains the cold during logistics (i.e. transport between acquisition and examination sites) is being investigated. Our research interests include the study of transport phenomena in single and multiphase systems that includes study of pool boiling characteristics during quenching in liquid nitrogen, melting/solidification processes in phase changing materials.

Health care logistics

Access to frozen biopsies is of tremendous importance to improve the treatment choices for patients. To perform contemporary molecular biology technologies, such as RNA testing or protein (kinase, protease, nucleic hormone receptor etc.) activity testing, fresh/frozen tissue samples are a prerequisite. In current practice, the shipping of temperature sensitive payloads typically use containers with coolants such as dry ice to protect the payload from hotter or colder ambient temperatures during transport. These containers are bulky and unsustainable due to loss of coolant as vapor to the environment. There is a clear need for an environmentally friendly or "green" container able to maintain the payload temperature within a narrow band and can operate without an electrical power source or without any type of active cooling. We developed a container consisting of multiple bilayers of phase change materials and insulation. Multilayers of phase change materials and insulation surpasses the individual performance of these materials.

A three bi-layer sub-zero transport container.

Further reading:

Colijn, B.A., Rios Cruellas, G., Hashemi-Shabastari, M., Janssen, X., Leij, A. van der, Leyte-Gonzalez, R., Vanapalli, S., Veldhuizen, P., Verbiest, G., Verhaagen, B. (2012) PamFreezer: a solution to enable frozen biopsy logistics. In: Physics with Industry 2012, 19-11-2012 - 23-11-2012, Leiden.

Vanapalli, S. & van der Leij, T., WO 2016/162451, International patent, October 13, 2016.

Vanapalli, S., Klünder, T., Hegeman, I., Tolboom, A.H., Brake, H.J.M. ter, “An apparatus to measure the thermal conductivity of insulation panels at sub-ambient temperature”, International journal of refrigeration, 74, 642 – 648, 2017.