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Research and Engineering Development

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Progress continues to be made with the new whole body vitrification system. Our metal contractor has completed work on the operating table cold stage, and more equipment has been interfaced to the computer system.

This system will allow an unprecedented degree of control over the whole body cryoprotection and vitrification process, and in particular it is hoped the cooling stage will allow deep cooling to -100C on the operating table, avoiding the time and warming that results from moving to another cooling system. This is just part of what is being accomplished with the Bina and Martine Rothblatt matching grant. It is hoped that the work will be completed enough for thorough testing by the start of the year.

Minor renovations are being made to suite 109 to accommodate this testing and the bypass and vitrification lab being assembled by Chana Williford. We anticipate substantial completion by the end of this month. Chana is also assembling formal experimental protocols for all our activities to ensure more than full compliance with regulatory requirements.

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New Freitas Publications

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Robert A. Freitas Jr., who will be speaking at our upcoming conference, has just published with three co-authors the most comprehensive analysis of the hydrogen abstraction tool (for diamond mechanosynthesis) ever written. It is published in the current issue of the Journal of Physical Chemistry, a prestigious mainstream chemistry journal of the first rank. The abstract at the ACS website is here. BerhaneTemelso, the lead author and PhD graduate student at Georgia Tech, won the Foresight Distinguished Student Award for his work on this paper. Alcor’s support is proudly acknowledged at the end of the paper and helped make this fine work possible. They also have a second paper in progress, with the same co-authors (which include David Sherrill and Ralph Merkle), probably to go to the same journal, analyzing the hydrogen donation tool.

Rob continues working on his “magnum opus” paper on diamond mechanosynthesis –a comprehensive study of all reaction pathways needed to build a basic adamantane cage (the repeating unit of diamond crystal) using positionally-controlled chemistry, and also to build and recharge all the tools needed for this. The analysis uses good quality ab initio quantum chemistry methods, has been in progress for 2 years, and has required thousands of simulation runs (with each run typically needing 10-20 hours to complete on a 2-3 GHz computer). The study is now about 80-85% finished and sufficient useful pathways for building diamond have been found. The paper will be submitted and published sometime in 2007 and will provide the first well-checked clearly-defined theoretical procedure for building diamond (and building all necessary tools), using mechanosynthetic tools, that has ever been published.

Some of Rob’s recently published papers, which directly acknowledge Alcor’s support whenever format permits, are available online as follows:
(1) Robert A. Freitas Jr., “Pharmacytes: An Ideal Vehicle for Targeted Drug
Delivery,” J. Nanosci. Nanotechnol. 6(September/October 2006):2769-2775.
(Description of another new nanorobot, called the pharmacyte, published in a
mainstream peer-reviewed nanotech journal.)
(2) Berhane Temelso, C. David Sherrill, Ralph C. Merkle, Robert A. Freitas
Jr., “High-level Ab Initio Studies of Hydrogen Abstraction from Prototype
Hydrocarbon Systems,” J. Phys. Chem. A 110 (28 September 2006):11160-11173.
Abstract.
(3) Jingping Peng, Robert A. Freitas Jr., Ralph C. Merkle, James R. Von Ehr,
John N. Randall, George D. Skidmore, “Theoretical Analysis of Diamond
Mechanosynthesis. Part III. Positional C2 Deposition on Diamond C(110)
Surface using Si/Ge/Sn-based Dimer Placement Tools,” J. Comput. Theor.
Nanosci. 3(February 2006):28-41.
Full Paper
(The final Zyvex paper evaluating the use of our proposed dimer placement tool to add carbon atoms to build diamond structures — the paper reports that the tool should work well.)
(4) Robert A. Freitas Jr., “Nanotechnology, Nanomedicine and Nanosurgery,”
Intl. J. Surgery 3(December 2005):1-4.
Full Paper
(An invited editorial for a noted surgery journal, discussing nanorobotics for surgery.)
(5) Robert A. Freitas Jr., “What is Nanomedicine”” Nanomedicine: Nanotech.
Biol. Med. 1(March 2005):2-9.
Full Paper
(First paper in the first issue of the first major mainstream journal on nanomedicine.)
(6) Robert A. Freitas Jr., “Current Status of Nanomedicine and Medical
Nanorobotics (Invited Survey),” J. Comput. Theor. Nanosci. 2(March
2005):1-25.
Full Paper
(An extensive invited survey article on the field of nanomedicine.)

alcor

Betty Bulk Tank’s first fill

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Today we took a major step in improving patient care, in that we filled our new 900-gallon bulk tank for the first time. This poor tank had been neglected for several years for several years before we spotted it on the web; it had even been exposed to the elements since before our purchase in July, 2003. When we finally rescued it in November, 2005, it had rust spots, broken valves, and a large layer of dust.

Betty cost $12k when newly-used and can hold 900 gallons. She cost more than $3k for shipping and off-loading, and $2500 for repair and restoration. When new, these tanks go for $45k, not including shipping/off-loading. We like the price, and we like the added comfort of additional nitrogen on-site.

Hugh Hixon has been working hard to restore it to operational status. He changed the vacuum valve and modified the tank to accommodate nitrogen (originally configured for oxygen); and though we’re still working on plumbing the patient care bay for the patients, we decided it was time to partially fill the tank. I won’t comment on how we watched the wrong gauge, and filled nearly-full as opposed to part-way. …

We were only certain she was ready to fill, because Hugh had been testing — and fixing — the vacuum for many weeks. The first thing he did when it landed on the doorstep was apply a vacuum gauge and pump. Checking the vacuum pressure and the quality of the insulation were the quickest way to establish how much the refurbish would cost us.

At first, the vacuum gauge read more than we would have liked. We measured over 40 microns of gas pressure. Using a vacuum pump, we tested the insulation. That +40 micron measurement was not sustained as we continued to pump. Once the reading was below 1 micron, we stopped the pump and checked to see how the pressure responded. It rose, but with ever smaller slopes. If the vacuum has risen with consistent slope, we would have known that it was a leak, even if it was a slow leak. That this slope declined in steepness indicated a different problem.

The “getter”, a chemically-reactive lining in the vacuum that resembles kitty litter, has collected too much gas over the years and was releasing those bubbles into the vacuum. With each declining slope, we were seeing improvement in the filter these tanks have. Isolating the problem to this saturated filter was a good thing. It got better.
We waited to order a fill until the getter seemed appropriately out-gassed. And we decided to test fill.

Today’s fill was not without incident. Hugh and the nitrogen-supplier technician (an all-around useful cryotech guy) were both on hand to supervise the fill. One valve needed immediate replacing. That was accomplished with supplies on-hand. We also discovered a minor problem with a threaded valve. Replacing this valve requires we drain the tank, and we’ll be filling our portable dewars for some time to come. All nitrogen level maintenance will be done off the new tank until it’s low enough to replace the damaged valve.

Before people panic, this bulk storage tank has already been measured at better-than-industry standards of holding a vacuum of 4 microns for more than 24 hours. We’ll fix the valve, and more nitrogen will be available to the patients on demand.

All told, this project has cost us $12k, +$3k for shipping and off-loading, and $2500 for repair and restoration. Restoration is still on-going, insofar as it needs a fresh coat of paint. This will be done soon, and the patients will be moved in a week; bulk tank ready or not.

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M22 Implementation

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Alcor has implemented a new whole-body cryopreservation procedure which uses a new cryoprotectant solution, M22, licensed from 21st Century Medicine. The new cryoprotectant is perfused throughout the entire body using the same procedures required for glycerol cryoprotection; but while it cryoprotects the torso, arms, and legs, we are confident that it is also vitrifying the brain. The main difference, beyond the composition of the solution, is that neurovitrification can be done without separating the brain from the rest of the body.

This new whole-body procedure will now be standard for all members currently signed up as whole body, as well as for those whole body members who have executed an open option contract.

The important thing to realize about this process is what it cannot do. This is not whole-body vitrification, in the sense that the entire body is vitrified. Significant portions of the body do not cryoprotect sufficiently to vitrify, mostly because things like fatty tissue and skeletal muscle are not well-vascularized. This new procedure may not be as optimum for brain cryoprotection as a simple neuro procedure would be, because of the somewhat longer cryoprotection and cooling times. Conversely, compromises needed to protect the brain may lead to under-cryoprotecting the body, in less ideal cases. But the good thing to remember is that brain vitrification is now available to those who wish to remain strictly whole-body, and that the entire body is cryoprotected intact.

A significant amount of engineering work was done here at Alcor to ensure the proper use of M22. A new circulating chiller and perfusion circuit were needed, as were controlled-temperature enclosures for both the patient and the perfusion circuit to allow safe perfusion at temperatures well below the freezing point of water. The patient enclosure allows further cooling after cryoprotection, to at least -30 or -40 Celsius, reducing the hazards of temperature fluctuations while moving the patient into the next stage of cooling. The credit for this engineering work belongs to Hugh Hixon and Tanya Jones, who have done a wonderful job implementing the new procedure.

Those interested in neurovitrification and whole body cryoprotection will no longer have to face the sorts of compromises they did in the past, and we believe this is a significant advance in our capabilities. For those who would like to know more about M22, the composition and effects have been published in the scientific literature listed below [reference 1]. Electron micrographs of the ultrastructure of brain tissue vitrified with M22 have also been published [reference 2] and are available on the Alcor website at http://alcor.org/library/alcor-new-york-academy-of-sciences-paper/.

Further information and micrographs explaining the switch to M22 technology for all Alcor cases can be found on our website at http://www.alcor.org/library/new-cryopreservation-technology/.

As explained in reference 1, M22 has been shown to be compatible with high viability of tissue slices and with consistent survival of kidneys after transplantation. This allows the unprecedented vitrification of the human brain within the intact human body using a solution that is in principle capable of preserving tissue viability as measured by present-day methods. However, to be sure that the brain will vitrify in compromised human patients, Alcor currently must perfuse M22 for longer periods of time than those shown to preserve viability in model systems. In addition, M22 has not yet been shown to preserve the viability of the brain in model system studies.

Nevertheless, the use of M22 allows Alcor to come closer than ever to achieving the goal of in situ brain vitrification using perfusion conditions that preserve tissue viability by current standards. It keeps Alcor on the road to the possible, eventual attainment of this goal. [SVS/TJ]

(1) Fahy GM, Wowk B, Wu J, Phan J, Rasch C, Chang A, Zendejas E. Cryopreservation of organs by vitrification: perspectives and recent advances. Cryobiology. (2004) Apr;48(2):157-78. http://www.21cm.com/pdfs/cryopreservation_advances.pdf

(2) Lemler J, Harris SB, Platt C, Huffman TM. The arrest of biological time as a bridge to engineered negligible senescence. Ann N Y Acad Sci. (2004) Jun;1019:559-63. Review. http://alcor.org/library/alcor-new-york-academy-of-sciences-paper/

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Progress Toward Intermediate Temperature Storage

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In the previous Alcor News we reported that Alcor has acquired the prototype of an Intermediate Temperature Storage (ITS) device developed by Brian Wowk of 21st Century Medicine. (For an explanation of why ITS is desirable, please check the explanatory section in Alcor News #13 dated July 1st, 2003.)

Our new lab assistant, Todd Huffman, has been studying Brian Wowk’s design and has visited 21st Century Medicine to discuss reliability issues and possible modifications. Since the ITS pod will be cooled by positioning it above a pool of liquid nitrogen inside a Dewar, we have been debating which type of Dewar to use. An off-the-shelf industrial design is available, large enough to contain seven ITS pods (one in the center and six around it, in a hexagonal pattern). However, our proprietary “bigfoot” Dewar design is much taller, only slightly more expensive, and we have had extensive experience operating them over the past decade. A “bigfoot” seems our best option at this point.

In theory, it would be tall enough to contain a stack of three layers of ITS pods, with seven pods in each layer. The problem is that a tall Dewar will allow a more severe temperature gradient. In other words, the pods at the top will tend to be warmer than the pods at the bottom, and ITS requires that the temperature should be controlled with some precision.

One way around the problem is to use an internal framework of metal such as aluminum, which is a good conductor of heat and could minimize the temperature gradient. Another possibility is to fill the lower part of the Dewar with conventional neuropatients fully immersed in liquid nitrogen, with a single layer of ITS pods above them at the top. The disadvantage of this configuration is that we would have to modify our standard neuropatient containment shell. Also the ITS pods would get in the way during insertion or removal of neuropatients.

Another issue which Todd is investigating is the optimal refill system to maintain the reservoir of liquid nitrogen. A gravity feed would provide the security of constant refill without pumps, but would be grossly inefficient since the pipe connecting it with the Dewar cannot be optimally insulated and will promote nitrogen boiloff.

Using a pump for automatic refill sounds intuitively risky, but low-temperature pump design has been perfected in industrial applications, and a Dewar refill pump probably would run only for a few minutes per week. Two pumps could be installed in parallel for redundancy.

Todd has been tabulating every conceivable failure mode, including liquid-nitrogen level sensor malfunction (Dewar will boil dry), failure of temperature sensor inside ITS pod (patient may become too cold or too warm), wire-break failure, pod heater failure, control system failure, and many others.

Probably we will need four months to explore all these failure modes and develop satisfactory solutions, after which the construction and testing of actual patient storage units may take another two months. This is longer than we would like, but obviously the system must be absolutely reliable before we can offer it as an option to our members.

We can’t predict how much ITS will cost relative to conventional Dewar storage until we have established all the components in the system and have measured the liquid nitrogen boiloff rate.

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Intermediate Temperature Storage: A New Era at Alcor

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Maintaining patients at an intermediate temperature means keeping them warmer than liquid nitrogen, but cold enough to inhibit biological decay. For years we have wanted to provide this option. On June 14th, we came much closer to our goal.

Why Intermediate Temperature Storage is Necessary

If cryoprotective perfusion is performed successfully with a high terminal concentration, residual amounts of water in solution in the brain tend to solidify instead of forming ice crystals. When we use the vitrification solution which is now standard for all Alcor neuropatients, the entire brain should become a glassy solid as its temperature drops below the “glass transition point” around -125 degrees Celsius.

Traditionally, we have maintained our cryopatients at -196 degrees, the temperature of liquid nitrogen. We use liquid nitrogen because it is cheap, nontoxic, convenient, and requires no refrigeration equipment at our facility. The liquid is “precooled” when it is delivered. Unfortunately, it is colder than we would really like it to be.

When a cryopatient makes the long journey from -125 to -196 degrees, some portions of the brain inevitably tend to cool faster than others. This creates thermal stress which can result in fracturing. We use a “crackphone” to sense and record vibrations which we believe are an accurate indication of fracturing events.

Proponents of nanotechnology believe that fracturing will be relatively easy to repair in the future compared with cellular damage, but still we would like to prevent it. The problem probably can be minimized or even eliminated if the patient isn’t allowed to get so cold, and is held at a temperature just below the glass transition point. In other words, we would like our patients to be cold enough to vitrify, but not so cold that they start to fracture. Unfortunately the only easy way to achieve this has been by using an expensive laboratory freezer–until now.

A New Way to Maintain an Intermediate Temperature

On June 14th, in Rancho Cucamonga, California, biophysicist Brian Wowk of 21st Century Medicine gave a remarkable presentation attended by all Alcor board members and many staff members. Dr. Wowk has developed a simple, reliable design for an intermediate temperature storage device using a heavy-gauge metal container enclosed in a jacket of closed-cell insulating foam fitted with two 2-watt heaters. The insulating jacket is then immersed in liquid nitrogen, and the heaters are run variably by an external controller to maintain the desired temperature inside the metal liner, which conducts heat and minimizes the thermal gradient.

According to Dr. Wowk, seven of his storage devices will fit beside each other within the diameter of a typical “bigfoot” dewar of the design that Alcor uses. The initial cost of building each storage device will be around $2,000, but a greater expense will be incurred in the long term as the heating elements will increase the total boiloff of liquid nitrogen in the enclosing Dewar. Also, because of the foam insulating jacket, each intermediate temperature storage device will occupy a greater volume compared with a standard neuro container. However, we believe that many of our members may feel that a higher payment for longterm care is a very reasonable tradeoff if Dr. Wowk’s design minimizes or eliminates fracturing.

Alcor has purchased Dr. Wowk’s first prototype and will be testing it for reliability and boiloff. After we have the numbers, we will be able to offer intermediate temperature storage probably as an extra-cost option. We can’t estimate the precise cost at this time, but Alcor News will provide additional updates in the future.

This is the most exciting development in cryonics since the advent of vitrification, and we’re especially pleased by its simplicity. We believe there is an excellent chance that this will become the preferred method of patient care at Alcor.