I’m stuck at work for a while, so this is going to be painfully short, sorry.
The bit you’re missing is getting below the glass transition temperature prevents both heterogeneous and homogenous nucleation.
Dry ice is still well above the glass transition temperature.
Quickest online result I could find for the relevant graph is here: http://www.benbest.com/cryonics/vitrify.html, in section III. Axis labels are “Cryoprotectant concentration” and “Temperature (*C)”
(Although there’s a nicer graph Fig3, p36 in Wolker’s “Cryopreservation and Freeze Drying Protocols”, which just came out this month. Probably not online as of yet)
At very high cryoprotectant concentration (right hand side of the graph) you can transition from 0C to below the Tg without getting in either danger regions (heterogenous nucleation, and homogeneous nucleation).
At moderately high cryoprotectant concentration you can transition vertically from 0C to below Tg and only pass through the heterogeneous nucleation danger region, avoiding the homogeneous nucleation region. You typically do this as quickly as posssible, both CI and Alcor have computer controlled systems to accomplish this.
With no cryoprotection, or poor perfusion, you pass through the homogeneous nucleation region and ice formation is impossible to prevent.
A typical cryopreservation of a person would have both well and poorly perfused areas, so getting through even the ‘safer’ danger region of heterogenous nucleation is something you want to do as quickly as possible to prevent ice crystals forming.
/I’m not a doctor, this is just what I’ve gathered from looking at the research. Hope this helps :-)
Good point—I tried to note that in the second to last section. So, with standard amounts of cryoprotectant, I guess that sufficiently long patient storage at dry ice temperatures would just result in a super thin (nanoscale) layer of ice forming on basically all the nucleation-inducing surfaces (which could then all potentially grow with rewarming), right? That sounds bad, but I don’t have much intuition for exactly how bad that would be.
Yeah, sorry, I felt bad for not acknowledging that bit.
I guess that sufficiently long patient storage at dry ice temperatures would just result in a super thin (nanoscale) layer of ice forming on basically all the nucleation-inducing surfaces (which could then all potentially grow with rewarming), right?
Hmm.. that’s a really good question. Off the top of my head I don’t know where the actual amount of ice growth over time can be figured out. I’ll keep an eye out for more info.
Trouble is, I think, that (depending on perfusion) at −80′C it’s water is well below even a suppressed ‘freezing point’, but still well above the glass transition temp(approx −130′C). So the solution is strongly supercooled and looking for any excuse to shed energy by growing ice crystals, but still mobile enough to rearrange itself to make that happen.
My gut instinct is that it’d be a problem for ice formation on cooling, not just a future rewarming complication, but I’m not sure.
I’m going to go to the Alcor conference next week, if I have the chance I might pose that question to people there.
edit: formatting.
OK, here’s the gossip:
(again, I’m not a scientist, but I’m pretty sure nothing here is grossly misleading).
Some background: M22 is the formula used by Alcor, and VM-1 is the solution used by Cryonics Institute. Both are designed by professional cryobiologists, and M22 is patented (as well as being extensively used for cryoprotection of tissues in ‘regular’ labs).
There’s some info here: http://www.evidencebasedcryonics.org/2008/07/08/vitrification-agents-in-cryonics-m22/
VM1 is extremely stable against ice formation at dry ice temps of −80C. However it's more toxic, and wasn't designed for anything other than cooling down.
M22 is less stable at -80C, however it’s been incredibly cleverly formulated to minimize toxicity, and increase perfusion. It’s also got features (such as ice blockers) which come in most handy during the rewarming process, where a lot of damage can occur for cryopreserving organs, etc.
I heard from the designer, Dr Greg Fahy, that he’d run tests holding M22 at −80`C for a week without ice formation, and he gave the impression that too much longer than that might cause trouble.
So as far as long term storage goes, I’d say LN2 is going to be necessary rather than dry ice. However in the future things like Intermediate Temperature Storage (ITS) might make that even more attractive, by preventing fracturing damage.
As a person living in Australia, if I ever died unexpectedly (without having enough time to relocate to Scottsdale), I’d likely be preserved with M22 and sent via dry ice shipping. My take on it is that I’d rather have M22 (Alcor) than VM1 (CI), since good perfusion is so critical in getting a good vitrification in the first place.
Also just another thing that might be interesting:
Check out ‘intermediate temperature storage’, the idea of storing at a slightly warmer than liquid nitrogen temps (-130′C as opposed to −196′C) is a good idea in order to avoid any fracturing*. This is right near the glass transition temp, so no nucleation can proceed.
Tricky part is there aren’t any practical scalable chemicals that have a handy phase change near −130′C, (in the same way that liquid nitrogen does at −196′C) so any system to keep patients there would have to be engineered as a custom electrically controlled device, rather than a simple vat of liquid.
Not impossible, but adds a lot of compexity. They might end up doing it in a few years by putting a dewar in a dewar, and making a robust heater that will failsafe down to LN2 if there’s any problem.
*Personally I’m not concerned with fracturing, it seems like a very information-preserving change compared to everything else.
Tricky part is there aren’t any practical scalable chemicals that have a handy phase change near −130′C, (in the same way that liquid nitrogen does at −196′C) so any system to keep patients there would have to be engineered as a custom electrically controlled device, rather than a simple vat of liquid.
Phase changes are also pressure dependent; it would be odd if 1 atm just happened to be optimal for cryonics. Presumably substances have different temperature/pressure curves and there might be a thermal/pressure path that avoids ice crystal formation but ends up below the glass transition temperature.
I’m stuck at work for a while, so this is going to be painfully short, sorry.
The bit you’re missing is getting below the glass transition temperature prevents both heterogeneous and homogenous nucleation. Dry ice is still well above the glass transition temperature.
Quickest online result I could find for the relevant graph is here: http://www.benbest.com/cryonics/vitrify.html, in section III. Axis labels are “Cryoprotectant concentration” and “Temperature (*C)”
(Although there’s a nicer graph Fig3, p36 in Wolker’s “Cryopreservation and Freeze Drying Protocols”, which just came out this month. Probably not online as of yet)
At very high cryoprotectant concentration (right hand side of the graph) you can transition from 0C to below the Tg without getting in either danger regions (heterogenous nucleation, and homogeneous nucleation). At moderately high cryoprotectant concentration you can transition vertically from 0C to below Tg and only pass through the heterogeneous nucleation danger region, avoiding the homogeneous nucleation region. You typically do this as quickly as posssible, both CI and Alcor have computer controlled systems to accomplish this. With no cryoprotection, or poor perfusion, you pass through the homogeneous nucleation region and ice formation is impossible to prevent.
A typical cryopreservation of a person would have both well and poorly perfused areas, so getting through even the ‘safer’ danger region of heterogenous nucleation is something you want to do as quickly as possible to prevent ice crystals forming.
/I’m not a doctor, this is just what I’ve gathered from looking at the research. Hope this helps :-)
Good point—I tried to note that in the second to last section. So, with standard amounts of cryoprotectant, I guess that sufficiently long patient storage at dry ice temperatures would just result in a super thin (nanoscale) layer of ice forming on basically all the nucleation-inducing surfaces (which could then all potentially grow with rewarming), right? That sounds bad, but I don’t have much intuition for exactly how bad that would be.
Yeah, sorry, I felt bad for not acknowledging that bit.
Hmm.. that’s a really good question. Off the top of my head I don’t know where the actual amount of ice growth over time can be figured out. I’ll keep an eye out for more info.
Trouble is, I think, that (depending on perfusion) at −80′C it’s water is well below even a suppressed ‘freezing point’, but still well above the glass transition temp(approx −130′C). So the solution is strongly supercooled and looking for any excuse to shed energy by growing ice crystals, but still mobile enough to rearrange itself to make that happen.
My gut instinct is that it’d be a problem for ice formation on cooling, not just a future rewarming complication, but I’m not sure.
I’m going to go to the Alcor conference next week, if I have the chance I might pose that question to people there. edit: formatting.
Ok, well thanks so much for the comments, for offering to ask about that at the Alcor conference, and for being interested!
OK, here’s the gossip: (again, I’m not a scientist, but I’m pretty sure nothing here is grossly misleading).
Some background: M22 is the formula used by Alcor, and VM-1 is the solution used by Cryonics Institute. Both are designed by professional cryobiologists, and M22 is patented (as well as being extensively used for cryoprotection of tissues in ‘regular’ labs).
There’s some info here: http://www.evidencebasedcryonics.org/2008/07/08/vitrification-agents-in-cryonics-m22/ VM1 is extremely stable against ice formation at dry ice temps of −80
C. However it's more toxic, and wasn't designed for anything other than cooling down. M22 is less stable at -80C, however it’s been incredibly cleverly formulated to minimize toxicity, and increase perfusion. It’s also got features (such as ice blockers) which come in most handy during the rewarming process, where a lot of damage can occur for cryopreserving organs, etc.I heard from the designer, Dr Greg Fahy, that he’d run tests holding M22 at −80`C for a week without ice formation, and he gave the impression that too much longer than that might cause trouble.
So as far as long term storage goes, I’d say LN2 is going to be necessary rather than dry ice. However in the future things like Intermediate Temperature Storage (ITS) might make that even more attractive, by preventing fracturing damage.
As a person living in Australia, if I ever died unexpectedly (without having enough time to relocate to Scottsdale), I’d likely be preserved with M22 and sent via dry ice shipping. My take on it is that I’d rather have M22 (Alcor) than VM1 (CI), since good perfusion is so critical in getting a good vitrification in the first place.
Hope this helps!
Thanks so much for the info!
Also just another thing that might be interesting:
Check out ‘intermediate temperature storage’, the idea of storing at a slightly warmer than liquid nitrogen temps (-130′C as opposed to −196′C) is a good idea in order to avoid any fracturing*. This is right near the glass transition temp, so no nucleation can proceed.
Tricky part is there aren’t any practical scalable chemicals that have a handy phase change near −130′C, (in the same way that liquid nitrogen does at −196′C) so any system to keep patients there would have to be engineered as a custom electrically controlled device, rather than a simple vat of liquid.
Not impossible, but adds a lot of compexity. They might end up doing it in a few years by putting a dewar in a dewar, and making a robust heater that will failsafe down to LN2 if there’s any problem.
*Personally I’m not concerned with fracturing, it seems like a very information-preserving change compared to everything else.
Phase changes are also pressure dependent; it would be odd if 1 atm just happened to be optimal for cryonics. Presumably substances have different temperature/pressure curves and there might be a thermal/pressure path that avoids ice crystal formation but ends up below the glass transition temperature.
1 atm pressure has the advantage of costing nothing and requiring no equipment to maintain.