Most mid-career laboratory medicine professionals find it hard not to recall the days when DNA had to be extracted manually and polyacrylamide gels were mixed by hand without also reflecting on how fast things have changed. “You had to have a PhD and 20 years of experience before you could perform a nucleic acid amplification test, and now I can put it in the hands of a nurse or a patient care technician,” said Frederick S. Nolte, PhD, D(ABMM), F(AAM), director of clinical laboratories at The Medical University of South Carolina in Charleston.
Automation has come so far, in fact, that it is poised to disrupt the very structure of molecular diagnostics laboratories. New molecular automation systems are capable of connecting directly to clinical chemistry and immunoassay lines, potentially moving high-volume testing out of molecular diagnostics entirely.
“We have a vision to allow customers to move routine molecular testing to the most high-production environment and that’s in the core laboratory,” said Bryan Moore, PhD, director of marketing for molecular diagnostics at Roche. “It is a concept that is revolutionary, I would say, to consider doing molecular testing outside of an expert molecular lab.”
Moving nucleic acid testing out of molecular laboratories presents a unique challenge, not just in automation but also in controlling the risk for contamination. A little bit of hepatitis C virus (HCV) RNA carried from one specimen to another won’t make a difference in an immunoanalyzer, but would be a problem with molecular tests because their sensitivity is so high.
Nolte has explored this issue in depth. His laboratory uses Abbott’s m2000 system for molecular testing and also Abbott’s automation line. He wondered if he could take a single sample from HCV serological testing and also use it to perform molecular confirmatory testing.
His lab’s Abbott immunoanalyzer uses a single probe for every specimen, and even though it’s washed 10 times between specimens, Nolte suspected there was a risk that some nucleic acid could be left behind between samples. He conducted a study alternating HCV-positive samples with negative samples and found a very low level of cross-contamination in about 5% of samples. His lab went ahead with the new single-sample routine, but if the RNA result is below a certain threshold the staff asks for a new specimen.
These are the kind of issues unique to molecular testing that companies need to consider when designing automation systems, Nolte noted. “It’s really a different environment. The capacity of the technology—the really tremendous analytical sensitivity—makes it challenging to deploy in a core laboratory setting and make sure that you’re not generating false-positive results,” he said.
According to Moore, the onus is on in vitro diagnostics manufacturers to consider and to engineer their systems to prevent all forms of possible contamination. “You’ve got to figure out how to make it part of the instrument versus depending on expert techs to bleach and manage it on their own,” he said. “It’s shifting where contamination is managed, from a person to the automation.”
Roche’s Cobas 6800, with the right connection modules, already uses a single sample for serology and molecular testing, according to Moore. It also uses information technology to control the testing workflow and incorporates intelligent rules for reflex testing. “It’s a large piece of equipment, but we’ve consolidated multiple rooms of a molecular lab and even a refrigerator onto a single instrument,” he said.
Labs Face Tough Choices
Belinda Yen-Lieberman, PhD, who works as contract staff on clinical and molecular virology at the Cleveland Clinic in Ohio, said she is excited about what molecular point-of-care testing can do for patient care, but she is hesitant when it comes to the newest generation of “big box” automation.
Cleveland Clinic’s molecular laboratory uses Roche’s Cobas AmpliPrep and Cobas TaqMan, as well as the Hologic Panther system and instruments by BD, Qiagen, Siemens, and others. While Yen-Lieberman and her staff have looked at larger automated systems, they have decided they’re not ready for that level of consolidation. One instrument her team looked at was also very large—bigger than her office—and would cost as much as $1 million to set up, she noted, assuming the lab would need to buy a second instrument for coverage during maintenance or repairs.
With that said, Yen-Lieberman acknowledged that molecular testing will inevitably integrate with chemistry testing in the coming years and that automation will continue to improve the ability of the lab to do more with fewer people. “I do worry about retaining good, loyal technicians and making sure they are not bored,” she said. It takes hard work to keep her staff engaged, through continuing education and new opportunities to learn, because they want to do more than push a green button, she added.
At the same time, automation also allows laboratory staff to do more interesting work, such as next-generation sequencing, noted Karissa Culbreath, PhD, D(ABMM), scientific director of infectious disease at TriCore Reference Laboratories in Albuquerque, New Mexico. “We can do more because now I’m able to free up my extremely talented molecular scientists and molecular technologists to work on the next wave of clinical infectious disease tests,” she said.
Culbreath’s infectious disease laboratory, which performs about 75,000 to 80,000 tests per month, recently installed the Roche Cobas 6800. She, too, was hesitant to give up the variety of smaller automation systems and instruments. “It’s kind of been our claim to fame,” she said. “We often use many vendors for our instrumentation in clinical microbiology.”
Yet when Culbreath sought advice from her colleagues in chemistry and hematology who have already been through a transition in automation, she realized that they, too, had to make that choice and figure out a way to make it work. “It’s uncharted territory for a lot of clinical microbiology labs, but we can lean on the experiences from others in the lab to figure out how to make the system work for us,” Culbreath said. “When we break down those silos, that’s actually when I’ve been able to make the best decisions. Automation is not new, it's just new to clinical microbiology.
Managing the Coming Change
Consolidation is happening quickly now that manufacturers have created open channels to allow automated laboratory-developed tests and new features such as random-access testing, according to Gregory J. Tsongalis, PhD, HCLD, CC, director of the laboratory for clinical genomics and advanced technology at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. “I think the more consolidation we can have with automation, the better off we’re going to be,” he said.
Tsongalis isn’t worried about molecular testing moving out of molecular and infectious disease laboratories. “We’re anticipating that in a few years, all of our high- volume tests will be done in the chemistry lab,” he said. “I don’t have any issues around it because I think the expertise and the clinical utility in the test still resides with me and not with the directors of the other lab, even though the test is performed there. I think that’s one of the things that people need to start thinking about—getting over that it really doesn’t matter where the testing gets done, it matters who is interpreting those results.”
Molecular tests are increasingly available at the point-of-care, and soon a new wave of disruptive technology probably will bring them directly to consumers at home or in pharmacies, Tsongalis added. “I see my role and the role of clinical laboratory directors becoming more about data management, data mining, and interpretation versus the traditional role of performing lab tests,” Tsongalis said. “When you start democratizing lab testing, you start generating really big datasets.”
This represents a lot of change in a field where, not too long ago, lab scientists carried their manually extracted nucleic acids to hoods and carefully measured a microliter into Master Mix with so much focus that nobody could talk, Yen-Lieberman said. Now they hire non-degreed technologists to load samples into little blue cups and send them off on a conveyor belt.
Meanwhile, companies are now developing molecular instruments that almost anyone can use that offer test results in 20-30 minutes, Yen-Lieberman said, and companies are creating automation solutions with clever features, such as Bio-Rad’s strategy of anticipating add-on requests. Automation is improving satisfaction for patients, doctors, and laboratory professionals, Yen-Lieberman added. “Molecular automation will only continue to advance.”
Julie Kirkwood is a freelance journalist who lives in Rochester, New York. +EMAIL: [email protected]