CEO SUMMARY: Laboratory automation continues to develop in unexpected new directions. Recently, ARUP Laboratories and Motoman, Inc., collaborated to develop an automated thawing and mixing solution that integrates with ARUP’s existing automated line and replaces manual processes. Put into operation earlier this year, the automated work cell has improved the standardization of specimen preparation, directly contributing to a better quality test result.
LABORATORY AUTOMATION CONTINUES to make leaps forward, but not in the way envisioned by the pioneers who developed the first TLA (total lab automation) systems 20 years ago. Lab automation is evolving in a task-targeted manner, as illustrated by the latest breakthrough now in operation at ARUP Laboratories in Salt Lake City, Utah.
Earlier this year, ARUP installed two highly customized workcells that fully auto- mate thawing and mixing. Running side by side, each workcell processes 1,000 specimens an hour. The first one was installed in February, the second in September.
These workcells were a design solution to meet ARUP”s unique needs. As one of the nation’s major sources of esoteric and reference testing, its mix of specimen types and test menu require different work flow solutions to maximize quality, service, and operational efficiency. Recognizing the benefits that would result from automated thawing and mixing, Charles Hawker, Ph.D., Scientific Director for Automation and Special Projects at ARUP worked with Motoman, Inc., of West Carrollton, Ohio, to create an automated system. Motoman designs and builds robotic systems. It has customized robot solutions for a number of clinical laboratories in recent years. Since 2004, Motoman has provided robotic solutions to ARUP.
Specific Work Flow Need
“The development of this automated workcell evolved over time to meet a specific need in our laboratory,” Hawker explained. “As an esoteric and reference lab, our conveyor system transports and sorts specimens—just as other hospitals and labs do for sorting and processing specimens. In most settings, these conveyor systems connect equipment such as centrifuges, aliquotters, cappers/decappers, and sorting machines. They then transport specimens to analyzers.
“However, our large volume of esoteric and reference tests make it challenging to automate work flow in ways that support our needs,” continued Hawker. “As a reference lab, we get a substantial portion of our referrals as secondary specimens, compared with a primary lab that gets front-line specimens. Our assays are more complex and esoteric. Typically, we do our tests on platforms because these tests cannot be performed on analyzers connected to track systems.
“ARUP has another work flow requirement unique to a reference lab,” stated Hawker. “We receive a large proportion of frozen specimens that must be thawed before processing. These specimens must be thawed and mixed before they can go on the analyzers in our high volume laboratory. That is why we wanted an an automated solution for thawing and mixing.
“Half the specimens we receive must be thawed and all specimens must be mixed,” noted Hawker. “Having a well-mixed specimen to deliver to an analyzer is a standard process in every laboratory.
“It was about two years ago that we launched design and development efforts with Motoman,” he added. “The first design concept was abandoned because we didn’t think it would blow enough room temperature air at each tube to thaw the tubes quickly and uniformly.
“That was the point when we engaged the College of Engineering at the University of Utah,” Hawker added. “The university owns ARUP. and engineering has collaborated with us regularly. One of our ideas was to design a nozzle that would aim air directly at individual tubes to speed thawing and make the process more uniform than blowing air across an entire rack of tubes.
“The first design from Motoman had a general flow of air blowing linearly down the deck so the air would pass all of the tubes,” he explained. “But with this design, the air did not blow directly at each individual tube. That’s when we decided to use the individual nozzle design. Terry Ring, Ph.D., a professor in the Department of Chemical and Fuels Engineering, designed high-velocity brass nozzles, which proved to be a successful solution. Using this design positioned each specimen in front of one of these nozzles for thawing.”
Achieving Uniform Quality
The goal of the design team was to achieve uniform quality in specimen processing. “It is important to know that the goal in developing this customized automation solution was to enhance the existing work flow and support a high quality of thawing and mixing,” observed Hawker. “Our primary objective was not labor savings or a rapid return on investment (ROI). We wanted to use an automation solution that would produce uniform specimen quality and support existing work flow through our laboratory.
“Prior to this automation, the manual process involved putting blocks of 100 specimens on a benchtop and aiming a household electric fan at them for 60 or 90 minutes. That’s a common method of thawing specimens in esoteric and reference labs. With a fan, there is some certainty that all the specimens are thawed before mixing. However, there is no absolute guarantee that each tube will be thawed thoroughly because each tube is not individually inspected after the manual thawing process.
Complete Thawing Required
“Then, to mix specimens, a lab technician would put a piece of cardboard or similar material over the top of a block of specimens and mix them by inversion back and forth 10 or 12 times,” Hawker said. “Anecdotally, we knew that on rare occasions a client would call and say our results were not what he or she expected on a particular patient. They would ask us to repeat the test.
“We would repeat the test and get the results that matched the physician’s expectations,” he continued. “From this experience, we thought perhaps the explanation was that we had not completely thawed that specimen or mixed it well. In such situations, when the analyzer took a sample from the top of that specimen tube that was either not completely thawed nor completely mixed, it might get more water and not enough actual specimen, including the analytes, proteins, and the other serum constituents that are needed for a good test result.
“When a specimen is thawed, a layer is created based on the density of the elements in the serum,” Hawker added. “The proteins are on the bottom, and the top part is watery. That is why all tubes must be mixed before testing. But because thawing and mixing was a manual process, it was beyond our control to guarantee that we would never have an unmixed specimen Now, our automated thawing and mixing solution gives us confidence that every specimen is completely thawed and adequately mixed.
“Standardization is the key,” he noted. “It would be difficult for us to quantify the improvement in standardization. But we expect a decline in client calls to repeat any test results, as happened with manual thawing and mixing. Our automated mixing and thawing system now eliminates any chance of such errors, which is one reason we developed this machine.
“Each of our four main delivery tracks in our automation system transports a maximum of 2,000 specimens per hour,” he said. “One of these four tracks serves our highest volume laboratory section–the Automated Core Laboratory–the section for which we wished to implement automated thawing and mixing. In February, we installed the first thawing and mixing workcell, with the capacity to thaw and mix 1,000 specimens per hour. At that time, this was adequate to handle the peak flows on the automated testing line.
“By the beginning of the summer, ongoing growth in specimen volume justified the installation of a second automated thawing and mixing system,” he continued. “That unit was installed in September. With our two automated thawing and mixing systems running, we can handle considerable additional volume on our automated line now.
“Today, there’s no question that lab staff are happy to have these two thawing and mixing units running side by side,” he concluded. “They know the outcome is consistent thawing and mixing of specimens. Also, the machines have reduced the manual labor that formerly was spent thawing and mixing on the benchtop. And, we have removed the fans from the processing area.”
Craig Rubenstein, the sales manager for Motoman’s Lifesciences division, commented, “To our knowledge, this process has never been automated in such a flexible way. This flexible approach allows a lab to choose its own parameters, such as the length of time that a specimen is exposed to the air for thawing or the number of mix cycles performed on each tube before being returned to the conveyor. The lab can change these parameters as needed.
Guarantee Of Consistency
“For labs, the level of consistency it provides guarantees that every specimen is thawed and mixed according to a predetermined set of parameters,” Rubenstein added. “When it’s done manually, there are no guarantees of consistency, and labs accept that there is a wide range in variety of results. That is a significant development for the lab industry.”
THE DARK REPORT Observes that what ARUP and Motoman have developed is like the Holy Grail for esoteric and reference labs: a way to automate labor-intensive processes. This machine undoubtedly will lead to other, more sophisticated machines, thus leading to improvements in efficiency at all levels of processing in these labs.
Lessons Learned About Thawing, Mixing of Specimens Are Important for All Labs
WHEN DEVELOPING THE INNOVATIVE workcell with Motoman, Inc., ARUP Laboratories learned two critical factors about thawing and mixing specimens, said Charles Hawker, Ph.D., Scientific Director for Automation and Special Projects at ARUP.
“For clinical labs, this information about freezing and mixing specimens is critical,” he said. “First, everyone knows that when a specimen freezes, it expands. If the tube is too full, critical parts of the sample can be lost. Most lab technicians think they lose only a portion of the specimen, but the reality is different. Important components of the specimen are concentrated in the solutes that are lost. That’s because, as the tube starts to freeze, water molecules freeze first, pushing the solutes toward the center and out the top. For most testing purposes, we’ve determined that the specimen is ruined.
“We wanted to determine how full a tube could be and still go through the machine and be mixed effectively,” continued Hawker. “In our experiments, we overfilled and underfilled tubes. Then we measured thaw times and whether the samples were getting adequately mixed. As part of these studies, we did chemistry and albumin tests on these tubes. We consider the results to be important and want to share them with other laboratories.
“Labs are overpouring tubes all the time and freezing them for shipment,” he said. “They need to know the risk associated with freezing an overfilled tube. Even though this result was published in the 1970s, we wanted to share this information because there’s been a complete turnover of staff in laboratories since then.
“The second observation involved mixing,” he added. “As laboratorians, we are taught to mix specimens by inverting a tube 10 or 20 times. We wanted to know the minimum number of mixes the robot would need to mix the sample adequately. To our surprise, we learned only two mixes are required!
“We don’t recommend that laboratories change their mixing procedures, however,” he advised, “because a human doing the mixing is not necessarily mimicking how the robot does the mixing. The robot is timed to a specific speed and goes to a precise angle as it raises and lowers the tube for mixing.”
Steps in Automated Thawing and Mixing
WITH A THROUGHPUT OF 1,000 SPECIMENS per hour, the automated thawing/mixing workcell developed by ARUP Laboratories and Motoman, Inc., has a six- axis, robotic arm that gathers samples as they travel across an automated transport and sorting system.
For thawing, the robot places specimens in front of high-velocity, brass nozzles. The array of 760 nozzles blow room-temperature air at two liters per minute at each specimen. Air enters the standardized tube carriers (STCs) through a slit normally used to read bar codes. Each specimen is thawed from all sides in as little as 20 minutes. There are no detrimental effects on any analytes to be tested.
During mixing, the robot can hold 10 specimens at once and uses pneumatic, pressure-pin cylinders that clamp tightly on the tube caps, preventing leakage. It then rotates the samples through a 270-degree pattern, designed to thoroughly mix the specimens without air bubbles. After mixing, the transport returns the specimens to a sorter where they are arranged for testing to be performed.
To ensure that no aerosolized, infectious-viral particles could enter the laboratory’s air supply if a specimen spilled, an exhaust hood uses four high efficiency particulate air (HEPA) filters to displace air from the workcell at a rate that is approximately double the rate of air dispersed through the nozzles.