Industry 4.0—the fourth industrial revolution—denotes an era when many traditional manufacturing processes are becoming ever more automated, and using complex machine-to-machine interactions to introduce more efficiencies, better communications, and self-monitoring and diagnostics. Industry 4.0 has made its way to production of test results in clinical laboratories. Clinical chemistry, with its integrated analyzer systems, always has been a lab automation pioneer, although this mainly was limited to analytical units and standalone devices. Now, solutions that link several analytical platforms are building steam.

While automation doesn’t necessarily comprise all parts of the analytical process, total laboratory automation (TLA) combines into an integrated system full automatization of preanalytics, analytics, and postanalytics, such that specimens are processed, tested, and even stored with minimal user intervention. Labs worldwide are exploring or deploying varying degrees of TLA. 

In this first of a two-part examination of TLA, I explore the components of TLA, many of which have been implemented in my own lab at Inselspital – Bern University Hospital in Switzerland. TLA has four essential sub-processes: transport of samples to laboratories; preanalytical processing; transport of samples to analytical instruments and intermediate storage; and sample disposal.

From Bedside to Lab

In hospitals, automated sample transport to laboratories offers undeniable opportunities to improve processes and sample quality. Several technical solutions exist, including electrically operated small conveyor systems, pneumatic tube systems with collection containers, and transport of individual tubes.

TLA also doesn’t require unpacking sample containers. When a laboratory’s sample receiving department is operated 24/7 anyway, this might not be a problem, but existing staffing levels combined with incoming emergency samples—especially at night—can delay turnaround times if lab team members are not notified properly. For particularly sensitive samples, ultra-rapid sample transport can be problematic, so carefully evaluating acceleration forces acting on samples is essential.

Sample Checks

In TLA, preanalytical modules identify samples, sort out unsuitable or non-processable tubes, and mark specimens “arrived” in the laboratory information management system (LIMS). Ideally, the bar code on each sample facilitates this process. If the corresponding analyses have been requested electronically beforehand, a comparison between the LIMS and corresponding requests occurs immediately. This checks whether the material and corresponding patient are both correct, whether the quantity of tubes is sufficient for the planned analyses, and whether the time between blood collection and planned centrifugation is sufficient.

Otherwise, sample tubes can be moved to a waiting position. A further step checks the correct material coding. For example, if the bar code codes serum, the cap color of the tube must match. If necessary, TLA will perform a fill level check using the tube weight.

A Smart Path for Samples

After sample checks, a TLA routing engine assesses the sample path for each tube based on the list of requested analyses. The routing engine uses a comprehensive data table of all analyses that contains information about analyte, sample material, preanalytical requirements like centrifugation or aliquoting, minimum sample amount, analyzer, and priority ranking. Much of a TLA’s efficiency comes from smart sample paths based on this information.

Centrifugation, Decapping, Aliquoting

Centrifugation can be a time-limiting step, as centrifuges usually work with batches of samples. With TLA, however, operators can program a maximum waiting time and the centrifuge should start, even if it is not fully loaded. In the meantime, newly arriving samples will be redirected to another centrifuge.

In my experience, aligning centrifugation times for different analyses, such as clinical chemistry and coagulation testing, offers advantages. Whenever this is not practical, it might be reasonable to perform the first preanalytical steps manually and then introduce to the TLA already centrifuged samples. Since many analyzers can’t handle capped samples (depending on the vendor and system), samples are frequently transported in a decapped state. This is why most TLA systems include decapping stations. Open sample transportation, however, should be reduced to the necessary minimum to avoid sample vaporization, spills, or contamination.

TLA systems usually work sequentially by driving each sample from one analyzer to the next, rendering aliquoting modules optional for most systems. The number of aliquots can and should be reduced, as this supports patient blood management and reduces costs by saving aliquoting vials and storage space. Nevertheless, TLA-driven aliquoting works well when samples need to be transported to another laboratory or stored for biobanking.

Samples to Analyzers and Storage

After preparing samples preanalytically, TLA routing engines guide samples on tracks to attached analyzers that pipette samples directly out of tubes halted on a track. Alternatively, interface modules pick up samples and place them on vendor-specific racks, which are then inserted into analyzers. The latter require space and technical efforts, so labs would need to balance the benefit of automating the loading process against the necessary efforts. For less frequent analyses, specific TLA modules collect and provide the samples in specific racks connected with automated alarms, so staff members know when samples are ready to be picked up.

After the analysis, the TLA collects samples again and depending on their stability stores them in a refrigerated automated sample storage module. If new tests are requested on a stored sample, the TLA automatically puts the sample back on the track. TLA storage systems are self-organizing, and once fully loaded, the oldest samples can be sequentially discarded. An intermediate storage avoids traffic jams on the track and keeps samples accessible for reflex testing.

Part 2—to be published in the January/February 2021 issue of CLN—will explore what TLA can and can’t do, and prerequisites for and considerations in installing TLA systems.

Alexander B. Leichtle, MD, is associate professor at the University Institute of Clinical Chemistry and Directorate of Teaching and Research at Inselspital – Bern University Hospital in Bern, Switzerland. +Email: [email protected]