Automating the Clinical Lab

Automated systems—big and small—are changing the face of clinical laboratories  

By Steve Halasey 

Take a walk through any exhibit hall featuring clinical laboratory instruments, and it will be hard to miss the strong emphasis on automated systems. While new lab techs may still be trained to perform tests manually, most labs have moved forcefully to eliminate manual processes wherever possible. 

The reasons for the shift are manifold, including reduced staffing and budgets as well as the inherent inefficiencies of manual processing when automated solutions are available. 

Fortunately, manufacturers of in vitro diagnostic instruments and assays have been right on target when it comes to assessing and meeting the needs of today’s clinical labs. Below, we take a look at several of the ways that automation is helping to support clinical labs, with a few unscientifically selected examples from some of the major players in the field. 

Before and After 

For most clinical laboratories, the notion of automating processes starts small, with a need to streamline the everyday activities that are consuming so much staff time and energy. Beyond the realm of automated instruments that carry out the analytical phase of testing, a host of companies are engaged in developing solutions for both preanalytical and postanalytical processes, including bar coding, inventory, decapping, recapping, transport, storage, and more. 

But if any single process typifies the activities of a clinical lab, it would have to be pipetting—the essential method for moving liquid samples and reagents where they need to be in order to carry out testing. And naturally, a number of companies have created tools to help automate this task.

Integra Biosciences, Zizers, Switzerland, and Hudson, NH, is a global provider of high-quality laboratory tools for liquid handling and media preparation. The company is committed to creating innovative solutions that fulfil the needs of its customers in the medical and life sciences research, diagnostics, and quality control sectors. At the University of Zurich, researchers are using the company’s Viaflo 96/384 multichannel electronic pipette to streamline the experimental workflow of studies on Pseudomonas aeruginosa, a bacterium that commonly infects individuals with lung conditions, such as cystic fibrosis. 

“We recently completed an evolutionary experiment on Pseudomonas, to understand how a specific siderophore—a molecule which binds and transports iron in microorganisms—assists its ability to infect other organisms, and how environmental conditions affect the production of this compound,” says Alexandre Figueiredo, a PhD student in the department of plant and microbial biology. “The media for culturing different populations needed changing frequently, and so we required a system to make this workflow more efficient. I opted for the Viaflo 96/384 after seeing my colleagues using it successfully for high-throughput screening applications. 

“We used the Viaflo 96/384 for filling plates with sterilized media, conducting serial transfers, diluting cell populations, and transferring cultures to fresh media every 2 days throughout the 7-month experiment,” adds Figueiredo. “The ability to perform simultaneous pipetting of up to 96 or 384 samples saved us so much time; it only took 1 to 2 hours to do everything, compared to 6 to 8 hours manually. We also used the automated mixing feature, which saved further time, increasing our efficiency, and, importantly, standardized our method, because manual mixing procedures are never as reproducible.”

With all this attention being paid to pipetting, it was only a matter of time before suppliers began to fret about the potential for environmental damage caused by so much plastic waste. Grenova LLC, Richmond, Va, has taken on this challenge by developing a technology that enables labs to wash, sterilize, and reuse each pipette tip an average of 25 times. 

Since 2015, according to the company, labs have used its system to wash and reuse more than 62 million pipette tips, preventing 170,000 pounds of recyclable plastic from entering the environment and redistributing associated costs totaling more than $4.3 million. 

Considering that roughly 30% of a laboratory’s consumables budget is allocated to pipette tips, reuse allows for a reduction of up to 96% in annual spending. 

Self-Standing 

Not every instrument supplier aspires to automate the entire lab universe. Often, it’s a significant contribution just to automate well a process or group of tests that would otherwise be difficult or time-consuming to perform manually. 

In the middle of last year, Arlington Scientific Inc, Springville, Utah, received FDA premarket notification (510(k)) clearance for its ASI Evolution automated RPR syphilis analyzer—the first fully automated nontreponemal syphilis system for diagnostic testing and blood donor screening to receive agency clearance for marketing in the United States. 

According to Arlington Scientific, the ASI Evolution was designed as a low-cost analyzer for automating syphilis testing, increasing efficiency and output, and effectively reducing staff hours in the lab. The instrument interprets the results of 190 samples per hour, while delivering consistent, dependable, and objective results. A study found that the ASI Evolution reduced hands-on time by 92% when compared to a manual RPR test. With intuitive software, a single operator can run multiple analyzers simultaneously, freeing up time for other laboratory tasks. 

“We have always been focused on enhancing the quality and speed of diagnosing infectious diseases,” says Ben Card, president and CEO of Arlington Scientific. “In 2010 we created the technology for a semiautomated analyzer designed for the objective interpretation of ASI’s RPR card test. We further developed a fully automated nontreponemal analyzer, taking the knowledge learned and applying it to an automated platform.” 

The ASI Evolution enables laboratories to use the nontreponemal screening algorithm traditionally recommended by the Centers for Disease Control and Prevention with a fully automated assay, removing the need for a high-cost and complicated reverse algorithm. Screening with a treponemal test was previously introduced only because nontreponemal testing was not yet automated. Treponemal screening costs more, creates extra steps, and complicates the testing process. 

“The industry has needed a fully automated nontreponemal analyzer to efficiently use the traditional screening algorithm,” says David Binks, COO of Arlington Scientific. “The ASI Evolution delivers this standardization to the interpretation of syphilis testing, by removing the subjective visual reading and manual steps of RPR card tests.” 

Modularity

While self-standing systems play an important role in helping labs to automate specific processes and types of testing, automated systems also come in modular packages designed to work in sync with one another. As the consolidation of laboratory facilities across provider networks continues to reshape the sector, modular systems are a natural response that accommodates current needs while enabling capabilities for future growth. According to Beckman Coulter, Brea, Calif, new demands for automation take a number of different forms: 

• Demand for automation solutions that can manage high volumes of routine network testing while simultaneously maintaining the ability to quickly process stat samples from the emergency department or intensive care units. 
• Increased focus on preanalytical sample quality detection, as an increasing percentage of samples come from other sites within the network. 
• Modular design to enable capability for future growth. 
• Ability to manage diverse tube types to accommodate new tube types from acquired or independent facilities and practices.

Last August Beckman Coulter launched its DxM MicroScan WalkAway system, an automated diagnostic solution for bacterial identification and antibiotic susceptibility testing for microbiology laboratories. The system uses direct minimum inhibitory concentrations (MIC) for detection of antimicrobial resistance, offering confidence in results through gold-standard accuracy and the broadest first-time reporting. The system is designed to support microbiology laboratories that seek to optimize patient care, while reducing the risks, costs, and operational burdens of emerging antimicrobial resistance. 

“The DxM MicroScan WalkAway system gives our clinical laboratory partners the ability to identify emerging resistance with the highest levels of accuracy, ensuring optimal patient care,” says Joseph Repp, senior vice president and general manager of microbiology at Beckman Coulter. “Laboratories can have utmost confidence in the performance of our technology, which has been given number-one ratings by ServiceTrak for software ease of use and technical application support.” 

The DxM MicroScan WalkAway keeps laboratories at the forefront of bacterial identification and susceptibility testing with proven detection of emerging resistance to the toughest pathogens. At the same time, the system’s delivery of first-time gold-standard MIC accuracy helps laboratories achieve their operational goals by reducing costs associated with confirmatory—or offline—testing. Added workflow enhancements include a new fluid-level sensing technology for added assurance, easy-to-view external LED indicators that show status at a glance, quick bottle release that simplifies reagent maintenance, and integrated reliability improvements that maximize uptime. 

The DxM MicroScan WalkAway system is part of the company’s full line of microbiology solutions designed to guide critical patient decisions through proven accuracy. Automation and standardization of all core aspects of specimen testing creates workflow efficiencies for the laboratory, while reliable solutions deliver trusted results. 

Automating Molecular

The field of molecular diagnostics still sometimes feels like the new kid on the block, with the potential for unexpected discoveries and advances that are continuing to develop at a rapid pace. Today, such advances often come in the form of novel applications of next-generation sequencing (NGS), which is gradually making its way from research laboratories to everyday use in clinical settings. But the development of automated molecular analyzers over the past decade hints at the outlines of a field that is also maturing rapidly, sometimes displacing older methods of diagnosis, and other times developing entirely new approaches where none previously existed. 

In keeping with the needs of advanced molecular research and diagnostics laboratories, many companies have taken on the challenges of creating tools to automate complex tasks and streamline workflows. PerkinElmer, Waltham, Mass, has been among the most active players in this field. The company offers solutions spanning the genomics workflow, including nucleic acid extraction, liquid handling, sample preparation, DNA/RNA quantitation, library preparation, data analysis, and applications expertise.

“PerkinElmer’s applied genomics group is helping eliminate the challenges associated with genomic sample prep by providing labs with complete, single-source solutions encompassing everything from sample to solution,” says Arvind Kothandaraman, director of the NGS product portfolio at PerkinElmer. “NGS adoption is in full swing, but sample preparation remains a bottleneck for most labs. PerkinElmer is simplifying sample preparation by leveraging our core competency in automation and expertise in chemistry to provide a seamless upstream workflow solution for NGS users.” 

Last May, PerkinElmer launched its NextFlex unique dual index barcodes, the latest addition to its NextFlex family of library preparation solutions. NextFlex unique dual index barcodes are 192 barcoded adapters that provide unmatched data security in sequencing applications for use on Illumina platforms. 

The research use only system is specifically designed to mitigate index hopping and spread of signal, a known phenomenon associated with multiplexing that affects NGS technologies. Instruments utilizing a patterned flow cell and exclusion amplification technology experience increased levels of sample misassignment as a result. The NextFlex adapters address the important issue of sample misidentification, thereby enabling assurance of data integrity. By allowing researchers to pool multiple libraries in a single flow cell lane, multiplexing with the NextFlex barcoded adapters also significantly increases processing capacity, while reducing costs. 

“The NextFlex unique dual index barcodes are designed to increase sensitivity and flexibility, thereby allowing users to accurately differentiate between samples and maximize the use of an NGS run,” says Kothandaraman. “We take pride in enabling researchers to make scientific breakthroughs by providing innovative tools for their NGS workflow.” 

PerkinElmer has also been active in developing finished instruments for molecular diagnostics. Last August, the company announced a collaboration with Agena Bioscience, San Diego, to combine its LabChip GX Touch nucleic acid analyzer for quality assessment and quantitation of DNA in the upfront workflow of Agena’s MassArray system, a highly sensitive, mass spectrometry-based platform for high-throughput genetic analysis. The companies have focused on targeting circulating tumor DNA in oncology liquid biopsy, where the combined systems support a low-cost, yet highly robust, single-day sample-to-results workflow for laboratories. 

“We found the speed of Agena’s MassArray workflow and the sensitivity of their UltraSeek liquid biopsy assay to be an ideal pairing with the rapid quality assessment using our LabChip GX Touch system,” says Mark Dupal, PerkinElmer’s global portfolio manager of automation and microfluidics, applied genomics. 

PerkinElmer’s LabChip GX Touch nucleic acid analyzer provides accurate electrophoretic visual quality assessment and quantitation down to 25 pg/µL for DNA in as little as 30 seconds with flexible sample throughput options including 96-well and 384-well. The analyzer provides a streamlined upfront process for Agena’s 96- and 384-chip systems and the UltraSeek chemistry for liquid biopsy. 

“The LabChip GX Touch system gives our customers a new option to analyze DNA quality that is consistent with the overall value proposition that we offer,” says Mickie Henshall, vice president of marketing at Agena Bioscience. 

In evaluations performed by Agena’s scientific affairs team, the LabChip system ensured that sufficient DNA was present in the sample to achieve the sensitivity capabilities of the UltraSeek chemistry while efficiently identifying samples compromised by preanalytical variables that could result in false negative results. 

“Controlling preanalytical variables is an important component of delivering robust reproducible liquid biopsy analysis,” says Darryl Irwin, senior director of scientific affairs at Agena Bioscience. “The combination of LabChip GX Touch nucleic acid analyzer’s sample qualification with UltraSeek assay’s highly sensitive, multiplexed chemistry delivers a powerful liquid biopsy sample-to-result solution.” 

Also typical of such advanced molecular technologies is the BD Max system by BD, Franklin Lakes, NJ, a fully integrated and automated molecular diagnostics platform that performs nucleic acid extraction and amplification via real-time polymerase chain reaction (PCR). The system can multiplex up to 24 samples across multiple test applications and provides test results for most assays in less than 3 hours. Using BD Max products, laboratories can test for a range of conditions, including women’s health and sexually transmitted infections, enteric conditions, and healthcare-associated infections. 

With such an advanced platform in hand, the next challenge for molecular diagnostics manufacturers is menu expansion. Last October, BD added to its European test menu with the launch of a CE-marked molecular test for detecting tuberculosis and multidrug-resistant tuberculosis. The BD Max MDR-TB panel enables clinicians to simultaneously detect bacteria that cause tuberculosis and determine whether the bacteria contain mutations associated with resistance to two important first-line drugs, isoniazid and rifampicin. 

“We continue to focus on improving the diagnosis of tuberculosis so that we can provide clinicians with the best tools for identifying effective treatments for their patients,” says Nikos Pavlidis, vice president and general manager for molecular diagnostics and women’s health at BD Diagnostic Systems. “This new test is a big step forward for clinical practice, as antimicrobial resistance has made this identification more complex.” 

BD struck again last December, with the FDA 510(k) clearance of its BD Max enteric viral panel, a molecular diagnostic test for the direct qualitative detection and differentiation of enteric viral pathogens that cause viral gastroenteritis. The BD Max suite of molecular tests for the detection of gastrointestinal bacteria, parasites, or viral pathogens enables clinicians to perform targeted testing for patients based upon their symptoms and health history or exposure. The enteric viral panel is designed for targeted detection of the viral cause of infectious diarrhea symptoms in all care settings and can detect adenovirus, human astrovirus, norovirus, rotavirus, and sapovirus. Running on the BD Max automated molecular system, the enteric panels can return results in less than 3.5 hours, dramatically shortening time to results over traditional test methods. 

“We continue to expand our menu of unique, clinically relevant, molecular diagnostics panels to aid in diagnosis of a range of infectious diseases,” says Pavlidis. “We also offer panels for diagnosis of hospital-acquired infections, including Clostridium difficile and methicillin-resistant Staphylococcus aureus, as well as vaginal infections, common sexually transmitted infections, and group B streptococcal disease.” 

Qiagen NV, Hilden, Germany, and Germantown, Md, is also a major player in advancing the automation of molecular technologies. At the beginning of January, the company launched QIAcube Connect, the next generation of its widely used QIAcube instrument. 

QIAcube Connect offers greatly enhanced ease of use and efficiency in enabling any research laboratory to automate the first steps of molecular research workflows using Qiagen’s gold-standard spin column technologies for DNA, RNA, and protein sample processing. It also offers important new digitization capabilities and full connectivity—in particular via a tablet that enables researchers to stay connected with their instrument. 

Automation with QIAcube Connect ensures full standardization in purification of multiple sample types and frees researchers from repetitive and costly manual processing. 

“QIAcube Connect delivers a new level of excellence in complete automation for nucleic acid extraction and purification,” says Thomas Schweins, PhD, senior vice president of Qiagen’s life science business area. “With its enhanced digital capabilities and connectivity, QIAcube Connect offers a new level of utility and efficiency. The use of our gold-standard Qiagen technologies allows researchers to experience great confidence in the valuable insights they gain from their biological samples. Many research labs, however, are challenged by the increasing complexity of sample types and protocols. QIAcube Connect is an innovative solution that addresses these challenges through best-in-class automation, and will enable laboratories to become more efficient.” 

Among the key features and benefits of the system: 

• Automation of proven Qiagen spin columns. QIAcube Connect fully automates the lysis, bind, wash, and elute steps of Qiagen spin columns for DNA, RNA. and protein sample processing. Automation of the spin columns assures streamlined processes, as well as the benefits of enhanced reproducibility with reduced human error and less hands-on time. 
• Dynamic processing capabilities across an extensive range of protocols. QIAcube Connect is fully compatible with a range of Qiagen sample technologies, and can be used to automate more than 80 Qiagen kits with over 3,000 proven protocols. 
• Enhanced digitization and full connectivity. QIAcube Connect offers an enhanced user interface that provides a new dimension of utility. Full connectivity allows researchers to stay connected with their instrument, which enables quick response times, protocol review, and the ability to remotely monitor runs. 
• Highest safety standards. QIAcube Connect has been designed to ensure the highest safety standards for researchers. Fully automated worktable decontamination is built-in. Protocol controls and managed user access ensure data protection. Digital as well as barcode-enabled sample tracking and pre-run checks guarantee confidence in results. 

Total Lab Automation 

But perhaps your lab is ready to take the plunge into total lab automation. Recognizing that technology can play a critical role in addressing the challenges faced by clinical labs, Siemens Healthineers, Tarrytown, NY, brought to market the Atellica solution immunoassay and clinical chemistry analyzers for in vitro diagnostic testing. 

“Laboratories are facing major challenges: staffing shortages, budget constraints, and consolidation with other laboratories as health systems grow—while the number of samples they’re expected to run is increasing rapidly,” says Andy Olen, senior vice president of laboratory diagnostics for North America at Siemens Healthineers. “The Atellica solution was engineered with advancements never before seen in the clinical laboratory to address testing challenges with greater speed and efficiency to improve productivity so physicians can have their patients’ results faster.”

The Atellica solution produces results for the most common tests run in the laboratory: pregnancy tests, blood glucose, electrolytes, hormones, lipids, and many more. Laboratory staff are able to spend less time maintaining the analyzers as a result of their built-in quality control features that are important for delivering accurate results. 

The system enables healthcare facilities to achieve better outcomes at lower costs by transforming care delivery in the laboratory. With the flexibility to combine up to 10 components into more than 300 customizable configurations, to operate either as a standalone system or connected to Aptio automation, and to integrate seamlessly with other disciplines in a total laboratory solution, the Atellica solution offers scalability for long-term growth. 

The Atellica solution is a significant innovation for laboratories that frequently run emergency samples such as those used for cardiac emergencies. Laboratories will often dedicate both staff and instruments to priority samples to expedite results. Staff can now process patient samples by priority order with technology that transports each sample individually so that emergency samples can cut to the front of the line. Dedicated equipment and staff to process emergency samples quickly are no longer necessary. 

Atellica’s patented, bidirectional, magnetic sample-transport technology and multi-camera vision system for intelligent sample routing provide independent control over every sample, whether routine or stat. The immunoassay analyzer uses a dual incubation ring design, rigorous temperature and humidity controls of the reaction environment, powerful magnets for relevant particle separation, and robust washing protocols to deliver high throughput, while contributing to rapid and high-precision results. 

As in the case of molecular diagnostic platforms, menu expansion is a serious goal for the developers of total lab automation systems. In December, FDA granted premarket approval for 12 new assays to be performed on the Atellica solution. 

The infectious disease tests new to the system include HIV (HIV Ag/Ab Combo and HIV 1/O/2 Enhanced) and Hepatitis B and C (Anti-HBs 2, HBsAg II, HBsII Confirmatory, HBc IgM, HBc Total, HBeAg, and HCV). The new assays provide physicians with testing options for hepatitis screening, diagnosis, and monitoring. 

Each of the PMA submissions required extensive supplemental data and performance studies to demonstrate reliable performance on the Atellica solution. This accomplishment signifies the overall strength of the Siemens Healthineers assay menu. 

“These 12 PMA assays, combined with recently released high-sensitivity troponin I and procalcitonin assays, provide a comprehensive menu on the Atellica solution,” says Deepak Nath, PhD, president of laboratory diagnostics at Siemens Healthineers. “Laboratories seeking a broad menu supporting the needs of their clinicians and patients can now find it on the Atellica solution.” 

And the company isn’t done. Later this year, Siemens will unveil an integrated sample management suite for the Atellica solution to further enhance the sample management features already available. While development of the suite is still under way, Siemens sources say they expect it will provide new options to customize solutions for standalone, nonautomated Atellica solution configurations, including integrated decapping, a next-generation vision system, and integrated sealing. 

Conclusion

Manufacturers of systems used in clinical laboratories have whole-heartedly adopted automation—big and small—as the solution to many challenges faced by labs. But even a passing glimpse at the areas under development indicates that more advances in automation are certainly on the way. Laboratories seeking to right-size their technologies to their current and future workloads should have no difficulty finding systems with the right capabilities. 

Steve Halasey is chief editor of CLP.