X-Message-Number: 1695 Date: 30 Jan 93 20:14:48 EST From: Mike Darwin <> Subject: CRYONICS Reply to Jeffrey Soreff re Crac To: INTERNET: Date: 1/18/93 Several people have suggested I try to answer your questions about the glass transition phase, cracking, polymer reinforcement, etc. Herewith, I give you the short version. I don't have any complete answers. However, being never content to stop while I'm ahead, I'll go on a little bit further. The idea that weak glasses might be reinforced by a polymer is a clever one. I suspect, however, that it won't work for the following reasons: 1) We have for some time, used two polymers (one or the other, not both together) as 5% to 6% of the perfusate with which we cryopreserve both humans and research animals. These two polymers are hydroxyethyl starch (HES) with a mean molecular weight of about 500,000 and polyvinyl pyrrolidone (PVP) with a mean molecular weight of 40,000. Both bulk solutions and animals still crack. 2) While I am ABSOULTELY no expert in this area I think that the forces involved in generating fractures ARE significant. If specimins are cooled slowly you get large fractures, for instance I often saw fractures in rabbits completely severing the brain in several places and we observed fractures running over many centimeters in length completely bisecting the lung and liver in human cryonics patients. Add to this a recent Russian observation that flashes of blue light with measured temperatures in the thousand plus degrees range are observed when fracturing of solutions is carried out in the dark. I cannot emphasize enough my ignorance in this area. For instance, I do not know if HES and PVP are "strong" enough polymers. I would be delighted to carry out the experiment you suggest except that, at present, I have no access to liquid nitrogen. The work we do here is all in the - 100xC range or above (since we are trying to AVOID fracturing). Your second question about viability is a little easier to answer. There are many references which fairly uniformly document rapid deterioration of cells and tissues stored at -80xC or above (although there are a few interesting suggestions to the contrary). There are a small number of references that document fairly stable storage at -135xC or at -150xC (LN2 vapor temperature). The bottom line seems to be that these are both safe long-term (50 to 150 years) storage temperatures; the best evidence being that they are in common use in both ultra low temperature mechanical freezers and liquid nitrogen vapor freezers. However the story doesn't end there. When we propose storing very near TG, *how* near TG becomes critical. Some recent work by Fahy et al., suggests that when large masses of solution are cooled even a scant 5xC or 10xC below TG they crack. A lot of work needs to be done to evaluate the stability of water-cryoprotectant glasses at near TG. How mechanically stable are these glasses? Will the small nucleation sites known to exist in them grow over decades or longer periods of time (i.e., will they slowly freeze?). What kind of chemistry is going on in these glasses. And last but not least, what is the mechanical stability of these glasses over time. Anyone who has ever seen window glass in old ghost towns in Nevada will immediately understand what I mean: the pane is often thicker at the bottom and the glass has actually flowed over the frame a bit. Glasses kept near their TG may flow substantially with time. The experiments to help resolve these questions should be designed and started now. If you want a list of references of safe cryopreservation storage temperatures you may call me at (909)824-2468. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=1695