The instrument will provide faster analysis for medical and other biological research.
Historically, no matter what form a biological sample started out in, it had to be converted to graphite before being analyzed in an accelerator. The traditional AMS technology required operation by experts in disciplines far removed from medical fields, unforgiving special chemistries to prepare samples for analysis and extensive time required for that sample preparation - all factors that have impacted its utility for clinical researchers.
However, in recent years, Lab investments have allowed researchers to develop an interface that would handle liquid samples and bypass the graphitization process. The new bioAMS instrument will couple with this transformational technological development to rapidly and cheaply perform biomedical human subject tracer studies and body burden assessment addressing important questions in nutrition, toxicology, pharmacology, drug development and comparative medicine.
The instrument also will support LLNL's biological detection and medical countermeasures programs. Examples of applications include dating of cancer stem cells, developing individualized patient therapies and rapid testing of new therapeutics against infectious agents.
"AMS fills a special niche in the biomedical field because it can measure very low concentrations of drugs with extreme accuracy, and that's important for helping to understand how biology works. However, its real utility hasn't been fully utilized because of a variety of difficulties," said Ken Turteltaub, principal investigator (PI) of the NIH award and leader of the Lab's bioAMS efforts. "This new technology really moves AMS to the next level."
"In addition," said Ted Ognibene, co-PI of the NIH award, "the new instrument will shrink the standard sample size from half a milligram down to sub microgram levels. This drastically reduced sample size will allow researchers to better match the biological requirements of the experiment with the analytical capabilities of the instrument and open new fields of scientific inquiry that were previously closed with the graphitization approach."
These technological advances were driven by the specific needs of the biomedical community, according to Graham Bench, director of the Center for Accelerator Mass Spectrometry (CAMS). LLNL's National Resource for Biomedical Accelerator Mass Spectrometry works with more than 60 entities around the world on various studies.
"We've held workshops in the past two years for some of our major collaborators, and the number one technological request has been a more user-friendly front end to the instrumentation. They get valuable data out of the AMS, but the sample preparation process is a rather cumbersome step," Bench said. "We've listened to their requests in developing this instrument, because the end game is that they will be able to harness the technology much more effectively."
The new instrument will be the first AMS system at LLNL not housed in CAMS. Rather, it will be deliberately sited in the Lab's bioAMS experimental suite as part of the effort to move the technology out of expert accelerator laboratories into more routine biomedical laboratory settings. LLNL researchers will work to develop and validate the instrument with the goal of deploying the technology to general clinical laboratories in approximately five years.
LLNL's expertise in developing these types of technologies is why the instrument is sited at the Lab, Bench said.
"Livermore invented the field of biomedical AMS, we hold the patents, we are the world leaders," he said. "People come to us for advice and regard what we do as the gold standard for bioAMS. We've always had a reputation of being technologically innovative and they are relying on us to deliver on that yet again."
LLNL's culture of interdisciplinary work is key in maintaining that reputation for technological innovation, Turteltaub added. For example, the bioAMS instrument required researchers with backgrounds in physics, chemistry, biology and biomedical sciences to work closely together. "I don't think this would have happened in an academic or other environment because we truly do things in an interdisciplinary fashion," he said. "This required people with different backgrounds working side-by-side every day. Not collaborating once a week or month, but literally sharing space. This is an institution where the culture is to work right at the edge of what we know, beyond state-of-the-art."
This is only one example of the partnerships needed to create and advance this technology. On a larger scale, support from the National Institutes of Health, National Center for Research Resources, the pharmaceutical industry and academic community were leveraged with Laboratory funding and support from LLNL's Global Security Principal Directorate, Physical and Life Sciences Directorate and Science and Technology office to make this instrument a reality.