A freezer failure can undo years of research before anyone notices. Labs typically rely on tiered cold storage: refrigerators near 4°C, -20°C freezers, -80°C ultra-low temperature (ULT) freezers, and liquid nitrogen tanks for long-term cryopreservation below -150°C. Once a ULT freezer starts to falter, the timeline is unforgiving. Samples can be gone within hours. For scientists working with irreplaceable biological material, that reality shapes how they operate day to day. New technology aims to close that gap. Some systems inject liquid nitrogen or carbon dioxide directly into a freezer that’s losing temperature. Researchers are also rethinking the solvents used to freeze samples in the first place, a separate but related problem.

Sokol Todi, Ph.D., chairs the pharmacology department at Wayne State University School of Medicine, where his lab studies the molecular mechanisms behind age-related neurodegenerative disease. His group relies on fly genetics, mammalian cell biology, and biochemistry, while also working with post-mortem human tissue and mouse brain samples to study these conditions.

For a lab like his, the -80°C ULT freezer may be the most critical piece of that cold storage infrastructure.

Irreplaceable, mostly

The post-mortem human tissue in Todi’s freezers is gone for good if it’s lost. The mouse brain samples could eventually be regenerated by breeding new animals and repeating years of work, but few labs could absorb that cost. Either way, “we lose irreplaceable human samples and largely irreplaceable mouse tissue,” explains Todi.

His freezers also hold bacterial glycerol stocks, frozen fruit flies, and recombinant protein produced for enzymatic assays. That, too, would be a huge setback.

Todi doesn’t think of what his lab has as a cold chain, per se, but rather, a system of vigilance and webcams. Lab members keep the cameras trained on freezer displays and check them regularly, especially after hours, when no one is in the building to notice a problem in real time.

Prior to the webcams, a phone-call alarm system was meant to notify staff automatically when a freezer’s temperature climbed too high. Twice, it failed to call anyone.

“Thankfully, people were around to notice the high temp alarms,” he says. “We have not yet lost precious samples, but that is because of being super vigilant.”

When a freezer does start to fail, someone grabs the key to the lab’s dry ice supply and hopes enough is left. “It seems like there is not usually enough when you need it,” he says. People try to leave some behind for whoever needs it next. If dry ice can’t hold the freezer, the next move is finding space in a colleague’s -80.

One gap stands out to Todi. “I am not aware of a system that would enable swift and intact move of an entire freezer’s contents into another one without losing sample temps and without the use of large amounts of dry ice.”

A partial solution

Some backup systems solve this problem differently. Instead of moving samples, they stabilize the freezer itself. Eppendorf sells a few that connect to certain Eppendorf ULT freezer models and inject liquid carbon dioxide or liquid nitrogen automatically if the unit loses power.1 Carbon dioxide can hold a freezer between -50°C and -70°C, while nitrogen can get closer to -80°C.1 Thermo Fisher Scientific makes a similar system for its own TSX, Forma, HERAfreeze, and Revco freezer lines, with carbon dioxide adjustable down to -75°C and nitrogen down to -150°C.2 Like Eppendorf’s, it only works with the manufacturer’s own equipment.

Hampshire Controls sells a comparable device marketed broadly for labs, hospitals, and biobanks.3 That could make it a potential retrofit option for a lab like Todi’s, which relies on existing freezers rather than a new purchase built around backup capability.

Hampshire’s system has real limits, though. A single carbon dioxide cylinder provides just over 10 hours of backup cooling at -60°C, and the system’s battery lasts about 48 hours after a power outage. That buys real time during a short failure. But it doesn’t remove the need for someone to notice the alarm, refill the tank, or get the power back on before the buffer runs out.

Todi looked into backup systems like this once, and came away thinking of them as “a temporary solution, not sufficiently long to eliminate the need to move the samples anyway.”

Rethinking the freezing solvent

Another area of active research and development has to do with not just how samples are stored, but also the solvents that freeze them. Dimethyl sulfoxide (DMSO), the standard solvent for freezing cells and tissue since the 1950s, carries known toxicity concerns. But Todi’s lab still uses it.

Researchers have proposed several alternatives, including non-penetrating cryoprotectants like trehalose and sucrose, as well as other penetrating agents such as glycerol and ethylene glycol. More recent work has explored a range of DMSO-free strategies, including ice recrystallization inhibitors, membrane stabilizers, and cryoprotectants modeled on natural antifreeze proteins.4 Some of these alternatives are already sold commercially as proprietary formulations. STEMCELL Technologies, Sigma-Aldrich, and X-Therma all offer DMSO-free cryopreservation media without disclosing their exact substitute ingredients.

“If I were to choose between DMSO-free and better -80 backup, I would choose -80 every time,” says Todi. “We have not worried much about the toxicity effects for the work that we do.”

For his lab, the more pressing risk is not what solvent preserves a sample. It is what happens if the freezer holding that sample fails. Todi’s advice for new researchers reflects that same instinct: focus less on the products, more on the habits.

“Vigilance,” he says. “Tech can be nice and shiny, but human vigilance in my experience has been the only one that has not failed.”

References

1. Eppendorf. CO2 and LN2 back-up system: ultra low temperature freezer. Eppendorf. Accessed September 2026. https://www.eppendorf.com/us-en/Products/Cold-Storage/Cold-Storage-Accessories/CO2-and-LN2-Back-up-System-p-PF-56193

2. Fisher Scientific. CO2 and LN2 backup systems for ultra-low temperature freezers. Fisher Scientific. Accessed September 2026. https://www.fishersci.com/shop/products/co-ln-backup-systems-thermo-scientific-ultra-low-temp-co2-backup-system-factory-installed-for-use-forma-88000-herafreeze-hfu-t-revco-uxf-tsu-series/co4567

3. Hampshire Controls. Biomedical freezer backup systems. Hampshire Controls. Accessed September 2026. https://www.hampshirecontrols.com/

4. Ekpo MD, Boafo GF, Xie J, Liu X, Chen C, Tan S. Strategies in developing dimethyl sulfoxide (DMSO)-free cryopreservation protocols for biotherapeutics. Front Immunol. 2022;13:1030965.