Total Laboratory Automation (TLA) in Clinical Microbiology

Laboratory automation is a new and essential subject for clinical microbiologists. Though clinical chemistry laboratories adopted full laboratory automation over 20 years ago, diagnostic microbiology laboratories remained a manual and labor-intensive discipline until recently, owing to its inherent complexities.

Total laboratory automation (TLA) is a system that automates culture-based testing in the clinical microbiology laboratory. TLA in microbiology aims to refine quality, reduce the turnaround time, better manage an increasing number of samples, compensate for the reduction in skilled human resources, and be more economically practical. TLA in microbiology is evolving quickly. Currently, two companies provide different solutions for TLA in microbiology: BD-Kiestra and bioMérieux & Copan (WASPLab).

If the sample volumes are constantly increasing in your laboratory and you are always hiring new staff to meet the increased demand of the workforce. However, if you are not getting qualified staff, maybe it’s time to think about laboratory automation and maximize the productivity of your existing workforce.

Main Benefits of Total Laboratory Automation (TLA)

Major benefits of TLA are improved efficiency, consistency across the board, and standardization of test methods thus improving the overall quality and safety of laboratory testing.

1. Efficiency: In a manual microbiology lab, technologists/technicians spend a large part of their daily work hours doing repeated works that can be automated, such as sorting the plates, moving the plates, streaking the plates, and performing AST (antibiotic susceptibility test). With automation, the laboratory can process higher loads of specimens without increasing staff. Some of the duties, like reading cultural plates, and further working up in the culture plates, require the specific expertise of the personnel. They can focus on those particular duties if machines do the work of moving the plate around, not doing manual streaking and sorting of plates.
2. Benefits due to uninterrupted incubation period: In traditional microbiology workflow, plated culture plates spend an average of 3 hours outside the incubator depending on their journey in the lab (for reading colonies, gram staining, biochemical testing, etc.).  The incubator doors also open and closed many times. Both of these events affect the growth and recovery of microorganisms, especially the fastidious ones.
   In the TLA system, plates are incubated without interruption in an optimal atmosphere at an optimal temperature throughout the journey. As the plates are viewed as enlarged images on high-resolution monitors using multiple different lighting conditions, different types of colonies including small colonies won’t be missed. Many laboratories implementing TLA reported an exponential increase in the recovery of pathogens such as Staphylococcus saprophyticus, and Neisseria gonorrhoeae in urine samples.
3. Reduction in turnaround time (TAT). Due to uninterrupted incubation, all types of pathogens grow more quickly in the TLA system. This helps in median reduction of time to final results leading to patient care benefits. Infections such as sepsis and meningitis can be treated hours earlier with the right antibiotics. Decreased length of stay, decreased morbidity and mortality, and decreased costs are obvious benefits for the patient due to a reduction in TAT.
4. Quality: It cut down various types of human errors (such as errors during labeling of the plates) and increases the accuracy of the test results.
5. Uniform streaking: There is a lot of variation in streaking patterns between different technologists. This affects the number of colony-forming units.  In TLA, spreading the specimen across the plate is done in a very uniform manner.
6. Accelerates teaching program: TLA can help to accelerate the teaching program if the TLA implementing lab or hospital is also running a medical/technical school. Students can observe and compare thousands of digitally imaged and archived culture plates and also can go back in time and see how the colonies looked initially. A plethora of available information will aid in the teaching/learning process.

BD-Kiestra

The BD-Kiestra is a conveyer-connected system for the processing of both liquid and non-liquid samples.

BD Kiestra TLA system comprises the following work steps/modules:

1. SorterA (media storage with a capacity of up to 48 different media types and distribution)
2. BarcodA (barcoding),
3. InoqulA (specimen processing and inoculation): BD uses rolling-bead technology for streaking the sample. It is claimed that it generates 3-5 times more isolated colonies than loop-based methods and reduces sub-culturing.
4. The two-way ProceedA conveyor system links together these modules. ProceedA delivers barcoded plates from Sorter A/BarcodA modules to InoqulA for fully automated (FA) or semiautomated (SA) inoculation or to workbenches for manual inoculation of specific specimens or for subculture of growing microbial colonies. The ProceedA conveyor system connects InoqulA and ErgonomicA workbenches to ReadA compact incubators for plate incubation and imaging. Plates that require downstream follow-up work such as ID and/or AST are directly delivered via the ProceedA conveyor system to workbenches.
5. ReadA (normal atmosphere and CO2 incubators with digital imaging system): Each incubator has a capacity of 1,152 plates. The plates are stored individually in the incubator.
6. ErgonomicA: BD Kiestra’s TLA has integrated workbenches.

MALDI-TOF (MS) can also be integrated with the Kiestra TLA concept for the identification of organisms. Automated susceptibility tests and expansion with molecular diagnostics equipment (BD-Max) are in the planning stage.

WASPLab

The WASPLab (bioMérieux & Copan) is modular construction and connects the individual machines through a conveyer-connected system. The system processes smear, sputum, stool, and liquid samples. The WASPLab is composed of;

1. Specimen processing with the WASP (Walk Away Specimen Processor for specimen processing and inoculation)
2. A one-way conveyor system, and
3. Incubation in aerobic and carbon dioxide (CO2) atmospheres, and digital imaging. An incubator has a capacity of 800 to 1,760 plates with a single-plate location.

Preparation is being made to incorporate identification using MALDI-TOF (MS) and automated susceptibility testing into the WASP Lab system.

Digital Imaging

Digital imaging with a high-resolution camera system is one of the central components of TLA. The laboratory can determine at what intervals the culture plates are photographed. The plates can be viewed and labeled on-screen for further processing such as microbial identification or antimicrobial susceptibility testing.

Digital imaging software is designed to simulate and improve the visual assessment of organism growth. Each system can take pictures of plates with several exposures and at various angles. With the incorporation of digital imaging and the automation of MALDI-TOF (MS) identification, the percentage of plates needing manual processing can be greatly reduced.

Digital processing facilitates early detection of organism growth and shortens the time of identification. Decision-making can be automated for certain criteria, e.g., growth or no growth. In addition, all samples from one patient, e.g., urine, sputum, and multidrug-resistant organism screening, can be evaluated simultaneously with computer-assisted processing. Lastly, images can be archived and later used for training or for QC programs.

Limitations of Total Laboratory Automation (TLA)

Not for all types of samples

Generally, automation systems are most efficient in handling liquid specimens such as urine specimens. Specimens needing special processing methods, such as organ or tissue biopsies, are not easily accommodated by an automatic system. However, the possibilities for automatic processing can be expanded considerably through the use of liquid-based specimen transport systems. This effectively converts a very high volume specimen, the swab, into a liquid specimen that can be easily managed with an automated processor.

It may not be for labs of all sizes

The initial investment for the implementation of TLA is very high. Small laboratories may not be able to allocate the needed budget for initial setup. Enhanced expenditure for supplies, space requirements, and infrastructure constraints may not outweigh the benefits of automation for small laboratories.

The higher the complexity of the system the greater the risk of system failure.

Consequences if the system fails

The use of a central automated system may represent a major challenge for clinical microbiology laboratories if that system fails. Support and maintenance contracts are essential and manufacturers should be able to quickly fix technical failures within a couple of hours. The unavailability of spare parts and technical experts to fix issues may render the laboratory facility dysfunctional. To maintain a laboratory activity in case of major failure, the lab should retain a minimal backup laboratory setup such as conventional incubators and test systems.

Dependency on machines

TLA increases the chance of skilled human resources relying upon devices for minute work. The dependency results in the loss of the acquired skills of the conventional method in the long run. It creates problems during downtime as the processing of urgent samples will require shifting to traditional methods. The lack of efficiency in processing critical samples may jeopardize the patients’ health. 

References and further readings

1. Croxatto A, Prod’hom G, Faverjon F, Rochais Y, Greub G. Laboratory automation in clinical bacteriology: what system to choose? Clin Microbiol Infect. 2016 Mar;22(3):217-35. doi: 10.1016/j.cmi.2015.09.030. Epub 2016 Jan 20. PMID: 26806135.
2. Croxatto A, Dijkstra K, Prod’hom G, Greub G. Comparison of Inoculation with the InoqulA and WASP Automated Systems with Manual Inoculation. J Clin Microbiol. 2015 Jul;53(7):2298-307. doi: 10.1128/JCM.03076-14. Epub 2015 May 13. PMID: 25972424; PMCID: PMC4473203.
3. Lippi, Giuseppe and Da Rin, Giorgio. “Advantages and limitations of total laboratory automation: a personal overview” Clinical Chemistry and Laboratory Medicine (CCLM), vol. 57, no. 6, 2019, pp. 802-811. https://doi.org/10.1515/cclm-2018-1323
4. Lainhart W, Burnham CA. Enhanced Recovery of Fastidious Organisms from Urine Culture in the Setting of Total Laboratory Automation. J Clin Microbiol. 2018;56(8):e00546-18. Published 2018 Jul 26. doi:10.1128/JCM.00546-18
5. Zhang W, Wu S, Deng J, et al. Total Laboratory Automation and Three Shifts Reduce Turnaround Time of Cerebrospinal Fluid Culture Results in the Chinese Clinical Microbiology Laboratory. Front Cell Infect Microbiol. 2021;11:765504. Published 2021 Dec 2. doi:10.3389/fcimb.2021.765504