Testing of several engineering developments is underway, including the Advanced Cryoprotective Perfusion System (ACPS), the patient enclosure, and the Air Transportable Perfusion system (ATP). The ACPS, which will enable computer control of the process of perfusing the body with cryoprotectants during cryopreservation, is being incrementally tested. Control code is in place for system calibration, perfusate flow rate, vascular pressure, temperature, concentration, and mixing reservoir fluid level. The patient enclosure, which will have the ability to cool a patient following surgery, is easily able to reach -110 degrees C. We’re cooling to -100 degrees C while the patient is still in the operating room because it reduces the patient’s exposure to toxic cryoprotectant at high temperatures. The patient will be moved for second-stage cooling down to -196 degrees C at a safer handling temperature.
Posts in category Research & Development
Renovations to Alcor’s lab spaces continue. A new protective coating was applied to the floors, the walls have been painted, and new cabinets have been installed in the cardiopulmonary bypass lab, the large animal training room, and the dry lab. Countertops will be added next. Despite the disruption caused by renovation, Chana de Wolf was able to complete three surgical training sessions in preparation for her upcoming experiments.
Additional facility improvements, including a fresh coat of paint for the building and a new layer of asphalt for the parking lot, were provided courtesy of Cryonics Property, LLC.
Alcor has redesigned its portable ice bath (PIB) and is in the process of replicating it. Some minor modifications are being made to the original design, mostly with regard to the choice of wheels and the upper railing.
To expand upon the regrettably cryptic message posted recently on our whole-body perfusion system development, we are nearing completion on building the new perfusion system for whole-body vitrification. All of the necessary perfusion elements have control systems now, i.e. the computer can control the temperature, pressure, flow, refractive index and more. We are at the point of adding the alarm conditions and constructing the user interface. We fully expect to have this prototype available for demonstrations by the conference, in time for the facility tours.
We are still working on the new operating table design, and this perfusion system is independent of that.
We must yet rigorously test the new system to make sure it works as intended. The current state of this project is something that we will discuss at the conference as well, so that people understand what they are looking at during the tours.
The end of the year is coming fast, and with it the thought of tax time and another matching grant for Alcor research. Last year, the Bina and Martine Rothblatt Matching Grant was a resounding success, raising $200,000 for research and development related to whole body vitrification. Now we have another opportunity for our supporters to help us in our quest for better cryopreservations. But first, I want to say a little about what was achieved with last year’s grant.
In the past year, we have made steady progress with these projects described in the grant announcement:
* Laboratory Perfusion System: We are almost finished assembling our new lab space and small animal perfusion system, and experiments related to whole body vitrification and cryopreservation will begin shortly.
* Whole Body Cryopreservation System: A new human whole body cryopreservation system is nearing completion, which will significantly improve the quality of cryopreservation and the degree to which whole body patients vitrify.
* Low Temperature Transport: We have begun contract work with a California cryogenic engineer on a low temperature transport container that will allow vitrification and partial vitrification cryopreservation from remote locations, which is of particular interest to our overseas members.
Over half of last year’s grant still remains, to fund experiments and further engineering developments related to its purposes. All the expenditures from the grant were directly project related: not one cent has been used for overhead or regular employee salaries.
This year, a member who prefers to remain anonymous has put up $25,000 for another matching grant, this one focused on his own personal interest: fracture free storage. When a patient is cooled below the glass transition temperature (about -120°C), mechanical stresses form that can lead to fracturing of tissue, significantly increasing the level of technology needed for revival. Contrary to previous belief, we have found that simply maintaining a patient at higher temperatures may not be enough to prevent this damaging fracturing, since we have indications that fractures occur at temperatures too warm to be safe in the long-term.
To understand and seek ways to prevent these damaging fractures in our patients, Alcor has an ongoing project to analyze the biophysics of fracturing using newly developed technologies and methods. Your donation to this matching grant will support progress already underway, including ongoing testing and development of intermediate temperature storage and transportation systems. This research is separate from the whole body vitrification research, which is continuing into 2007.
From now until February 28, 2007, contributions up to a total of $25,000 will be matched by our anonymous donor. As usual, donations are fully tax deductible. This is your opportunity to further Alcor’s goals, double your contribution, and enjoy a tax deduction. Simply print and fill out the enclosed PDF form, or phone Alcor at 1-877-462-5267 ext. 101 with your credit card. We will do the rest.
Finally, I want to thank all our members for their continued encouragement and support over the last year. I think 2007 will be even better.
Stephen Van Sickle
Earlier this year, Alcor engaged in some long-term organizational planning. The result was the drafting of a three-year plan for development. Our plan broke operations into four main categories: membership, clinical readiness, research and technical development. It considered strategic positioning and facility improvements that would be necessary to transitioning Alcor from a small start-up into an organization that is capable of surviving successful outreach and mass marketing.
During the development of this plan, technical aspects had to be looked at in detail, because they affected nearly every department. Dr. Mike Perry, Alcor Patient Caretaker, prepared an analysis of the current membership and mortality statistics in an attempt to estimate the requirements for performing cryopreservation procedures at various membership growth rates. (See Cryonics, Spring 2006, for a brief summary of that analysis.) Dr. Perry’s analysis told us that we would face significant challenges if the membership grew faster than the technical capability could handle. His results encouraged us to hone our commitment to improving the foundations of our emergency response capability, in terms of both equipment and personnel. Once that infrastructure is in place, then we can consider improving the membership aspects and engaging in directed marketing.
Though the three-year plan itself will not be released in full because it was intended as an internal planning document (and will likely be subject to significant modification as time passes), we intend to update our members and supporters on elements that have been implemented or are being implemented in the near-term.
Research and Development
Aside from our standard administrative tasks and special projects like the conference, our time has mostly been spent on engineering improvements for the cryopreservation processes. We have begun automating collection of data during the cryopreservation process and control of the perfusion process, and this has necessarily included acquiring new equipment. In addition to progress made on those projects, we’ve needed to add a couple of items for the improvement of patient stabilization processes.
We’ve built a prototype of a partial liquid ventilation system for rapid cooling while performing cardiopulmonary support during a patient stabilization. Partial liquid ventilation is a process involving the introduction of a cooled, oxygenated liquid into the lungs, where the massive surface area can facilitate extremely rapid cooling. It’s partial ventilation, because the oxygen-carrying capacity of the fluid is insufficient to support metabolism, and so a patient has to have additional oxygen support.
Our mechanical system for partial liquid ventilation will allow us to cool patients during the critical first-minutes of the stabilization procedure, a vital capability that has the potential to drastically improve a patient’s overall cryopreservation. This system is expected to provide nearly the cooling rate of the blood washout, at an estimated half degree C per minute, with none of the invasive surgery or time delays. The prototype has now been submitted as Alcor’s first patent and is based on earlier work done at Critical Care Research. It is simpler to deploy, requires significantly less training to operate, is less expensive, and considerably more portable than any other device patented for this purpose.
We’ve also nearly completed a re-design of the portable ice bath (PIB), a lightweight bathtub on wheels which enables a patient to be cooled with ice and treated while being moved, such as in a hospital setting. The new design is based on an idea by Michelle Fry and was built by Randal Fry (with the help of Diane Cremeens). Our previous PIB was one of the least efficient pieces of our stabilization kit, and our new design should meet the requirements of being portable, easy to assemble, and capable of whole-body cooling. It should provide for more weight-carrying capacity than previous versions and has the bonus benefit of being able to go over curbs or a couple small steps and other surfaces, like grass, significantly improving our mobility. Once the design and testing of this ice bath are complete, we intend to replace all previous versions in the field. (We may actually build a couple extra units, because a local fire chief has expressed an interest in using one for their remote rescues and donating one to their cause would be good for community relations.)
Our research team is working hard on the development of a cardiopulmonary bypass laboratory. This development is important to beginning comprehensive testing of every aspect of the cryopreservation procedure, from the impact of different cooling methods or medications to the advantages and disadvantages of various cryoprotectants. Using our cardiopulmonary bypass laboratory, we intend to replicate the total body washout experiments performed by Cryovita and Alcor in the late 1980s and early 1990s in the rat model. We have acquired most of the equipment necessary to establish the model, and the protocols are being drafted for experimentation. Setting up the perfusion system has been the most complicated factor, and Chana Williford, Alcor’s Research Associate, has developed a design that seems likely to avoid one of the major problems of rat perfusion: priming volumes. This volume reflects the amount of fluid contained within the perfusion circuit, and should be as low as possible. Her circuit has an extremely small priming volume, and the design alone should be publishable in scientific journals if it holds up under scrutiny.
Intermediate temperature storage is something else we’re working toward and has been discussed for some time, but it is important to mention that providing long-term care of patients at higher temperatures, like -140 degrees C, does not actually eliminate fracturing in patients. We believe annealing, a process whereby strain can be relieved in glassy materials through raising and lowering temperature in a controlled fashion, may be the solution to eliminating fracturing in patients.
In order to test that hypothesis, we have completed construction on a prototype annealing test cell that will allow us to investigate the physics of fractures in our patients. We intend to begin testing our cryoprotectant next week. If this prototype is effective for its intended purpose, we will replicate it to allow for multiple samples to be processed during fracture experiments. Our hope is that we can develop a reliable protocol for minimizing – or even eliminating – fractures in our patients. This work is expected to take some time, as learning how to cool a pure cryoprotectant (our first step in the lab after building the equipment) is very different from learning how to cool a complex organ system.
In many ways, our research and development program is being built up from nothing. Lack of focus, changes in personnel and lack of serious commitment all contributed to poor development in technical areas in the past. Rather than leading the drive for improved cryopreservations, we were relying on external organizations for research and largely languished in areas of development. We have begun to repair this serious deficit and intend for the new research and development efforts to aid in our goal of becoming recognized as a serious scientific research organization.
Our new operating room has been assembled and is prepared to perform two cryopreservations simultaneously, one whole-body preservation and one neuropreservation. There are, however, two pieces of equipment that are not duplicated between the stations: the chiller (which provides cooling for the perfusion circuit) and the computer control system. We are not planning to duplicate the chiller, because it will be insufficient in the near-term to reach the depths of cooling that we have in mind for the new operating room table. The computer control system is being significantly re-designed; and once the new system is built and tested, that is the one we will replicate. Computer control will allow us to monitor more directly every aspect of the cryoprotection process; and alarms will be set to inform us when critical milestones are reached or if there are failures in the system. Aspects of the cryopreservation to monitor will include, but are not limited to, perfusion pressures, vascular resistance, cryoprotectant uptake and water loss, temperatures (naturally), and flow rates. This should allow for more comprehensive analysis of future cryopreservation cases.
Improving the emergency stabilization kits is also well-underway. We’ve designed a smaller version of the remote kit that will be more widely deployed, especially into new regions. This small kit will ensure the capability to administer surface cooling, cardiopulmonary support, and medications. It will not include washout capability at this time, as the more remote regions do not yet have personnel trained to carry out a washout procedure. The washout capability will arrive with Alcor personnel, in case of an emergency. Once the new kit has been tested in a field situation, then we will deploy it more widely. We intend to build twelve of these smaller kits, deploying them to places like New England, Nevada and Texas as supplements to fuller kits like the ones stored in California.
Expanding the field capability also requires training more emergency response personnel across the country and world. This expansion of the training schedule is well-underway. In 2006, we expanded training to include several regions, like Texas, Florida, and the United Kingdom. In 2007, we’re coordinating expansion to include Australia, New England, eastern and western Canada, and the Pacific Northwest. This will be in conjunction with the existing regions. Because this expansion will place a strain on personnel and training equipment, we’re strongly encouraging emergency response team members in the regions to gather periodically between Alcor-attended sessions, to review the training materials and practice the skills, and to contact Alcor when questions arise. Teams are responding well to this encouragement, and new people are contacting us nearly every week for training opportunities in their area.
And in Conclusion….
Much of this progress to date has been made possible because of the success of our matching grant earlier this year. It is still the case that the three-year plan is ambitious and will take significantly longer than three years to implement if additional funding is not obtained. We are cautiously optimistic about our chances for securing the necessary funding, because we’re improving our reputation for fiscal management; adhering to the financial controls that were set in place late last year; showing consistent progress on projects; and basically, sticking to the business at hand.
We still have a lot of work to do, but we have a good staff that is fully capable of handling the load. We’re pleased with the progress that has recently occurred, and we intend to keep the momentum going. Developing the plan has helped hone our focus on the things that matter, and everyone on the staff has great ideas on how to continue improving our procedures.
Needless to say, we’re excited about the current direction Alcor is headed, though we’re fully aware that there is still a tremendous amount to do. We hope you’ll stay tuned and see how this all develops.
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.
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.
(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.
(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.
(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.
(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
(An extensive invited survey article on the field of nanomedicine.)
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.