NEW YORK (GenomeWeb) – Having gained traction for its reagents in the research-use-only and laboratory-developed test markets, SISCAPA Assay Technologies is now looking to expand further into clinical markets.
According to Founder and CEO Leigh Anderson, the company is currently in the process of working out a partnership that will help it develop its reagents and assays for in vitro diagnostic applications.
"The reagents that we provide currently are strictly research use only," he told GenomeWeb. "The next stage is to put these together into regulated kits that could be submitted to [the US Food and Drug Administration] and used then very broadly in diagnostic laboratories."
That stage, Anderson said, will be handled through the partner the company is currently establishing. He didn't name the partner or potential partners.
SISCAPA — short for stable isotope standards and capture by anti-peptide antibodies — combines antibody-based peptide enrichment with mass spectrometry, increasing the sensitivity of mass spec instruments, which by themselves are often not sensitive enough to detect low-abundance proteins in complex samples. Additionally, by providing the mass spec with a cleaner sample enriched for the targets of interest, SISCAPA can reduce LC and instrument cycle times, upping assay throughput.
Mass spec is an attractive alternative to ELISAs for clinical protein biomarker detection because its multiplexing capabilities make it potentially less expensive. Additionally, mass spec assays often have better specificity than immunoassays, providing a higher level of confidence that the analyte measured is, in fact, the assay target.
Anderson launched SAT in 2011 to commercialize the technology, which he invented. Since its launch, the company, which currently has eight employees, has focused primarily on the pharma and CRO markets where it provides the assays as a research tool.
SAT has always intended to move into the clinical space, though, and with mass spec gaining clinical acceptance more quickly than he once expected, this move is coming "sooner rather than later,"Anderson said.
"It has become commercially viable a little earlier than expected," he said. "We have seen a lot of progress of mass spec toward acceptance in the clinical laboratory, and so that is something that we are pushing really hard."
SAT has moved its technology into the clinic in a limited way to date. For instance, Mayo Medical Laboratories offers mass spec-based serum thyroglobulin testing using SISCAPA technology.
Thyroglobulin is a prime example of a test that can benefit from a mass spec-based assay. Clinicians tracked the analyte in thyroid cancer patients to detect recurrence of the disease after surgery. Traditionally, this has been done with ELISAs or radioimmunoassays, but roughly 20 percent of patients develop autoantibodies against thyroglobulin that make it difficult to accurately measure levels of the protein with such tests.
For this reason, clinical labs including Mayo and Quest Diagnostics have turned to mass spec for thyroglobulin testing in the case of autoantibody interference.
Converting other similarly troublesome immunoassays to mass spec assays is a primary aim of SISCAPA's clinical push, Anderson said, citing IGF1 as another example.
He added that the company also hopes to drive a broader shift toward mass spec assays by developing over the next several years a SISCAPA assay menu covering essentially all clinically used protein markers currently measured in blood.
Anderson acknowledged that this second goal was something of a heavier lift, noting that "if [existing] assays look like they are working, it takes some doing to get people to switch [to mass spec]."
However, he said, the hope is that mass spec's cost and technical advantages will eventually lead clinical labs to transition over to the format even for immunoassays currently deemed suitable.
"There is a point at which [due to the cost advantages provided by multiplexing] the mass spec assay is going to be significantly less expensive than the immunoassay, and that is the point at which you can expect to see a transition over to running a broad menu on the mass spec," he said.
"The second thing is the galaxy of general technical advantages," he added. "You can multiplex easily; there are no issues about specificity. And those advantages are scientific and persuasive, but they really become super compelling once it is also less expensive."
Anderson said that he and his SAT colleagues had calculated that mass spec could begin providing cost savings compared to immunoassays at multiplex levels as low as two or three analytes.
In response to an inquiry from GenomeWeb regarding the potential benefits of mass spec not only for troublesome immunoassays but for protein tests more broadly, Nigel Clarke, senior science director for applied technology at Quest Diagnostics, wrote that the company looks "forward to continuing to push the bounds of mass spec's potential to deliver actionable health insights," though he did not comment on whether he expected the technology to be implemented as broadly as SAT hopes.
Clarke did note the challenge of clinical mass spec test development, saying that "while we believe strongly in the value of these technologies for many clinical applications, tests on mass spec can require a higher degree of skill both to develop and perform."
In its initial focus on analytes ill-suited to immunoassays, SAT is moving in a similar direction as companies like Nuclea Biotechnologies, which earlier this month discussed with GenomeWeb its plans to develop mass spec assays for analytes for which existing assays have poor performance.
Nuclea COO Mary Lopez was more circumspect, however, regarding the potential of mass spec to gain ground where there are already well-performing immunoassays.
"Not every test needs to be run on a mass spec — some tests you can do just as well with an ELISA," Lopez noted. "A mass spec really shines when you need to be able to measure different forms of the protein and so you need that selectivity the mass spec can give you," she added, citing as an example an insulin, proinsulin, and c-peptide test Nuclea has under development.
In addition to developing IVD-ready assays, SAT continues to pursue development of dried blood spot-based assays, which provide a potentially less expensive, more convenient alternative to conventional blood samples.
Dried blood spots typically consist of microliter volumes of blood spotted and dried on filter paper. They can be stored and shipped without refrigeration and analyzed by a variety of methods including immunoassays and mass spectrometry.
Because of their durability and ease of shipping, blood spots are an attractive form of sample collection for long-term, longitudinal monitoring of patients, an application that SAT is exploring in several areas, Anderson said.
Among these projects is an ongoing collaboration with the Brazilian Olympic Committee to analyze proteins in athletes for training and coaching purposes. The company is currently looking at dried blood spots collected from Brazilian athletes at the Pan American games ongoing in Toronto.
"In our catalog we have a number of assays to proteins that have interesting athletic implications," Anderson said, adding that "there are changes in the plasma proteome as a function of training and in the course of intense athletic competition that could be meaningful to the coaching staff."
"This is the sort of initial demonstration of this approach, being run right now," he said, noting that already dried blood spot samples are being sent to SAT's facility in Victoria, British Columbia, where researchers are generating results and returning data.
The company's more traditional clinical dried blood spot projects include work on cardiovascular markers where it is collaborating with researchers including Cedars-Sinai Medical Center's Jennifer Van Eyk.
It is also interested in exploring dried blood spot samples to track the progression of infections.
"We have been able to measure enough different components of the infection response pathway to [be able to] look at the course of infection and how to differentiate serious from non-serious infections, for example," Anderson said. "I think that will take a little more work to demonstrate the exact value of, but it is something we are very interested in going forward."