Three Current Trends in Automated Liquid Handling for Clinical Applications

Three trends in design and engineering have led to liquid handling innovations for the clinical lab

Multiplexing

Immunoassays, as a technology, have a dominant presence in clinical lab diagnostics. Traditionally, enzyme linked immunoassays or ELISAs have presented challenges for clinical adoption, due to the number of liquid exchanges and imaging optimization steps, among other complexities. Well-to-well and plate-to-plate precision has presented limitations as well, holding ELISA and other complex immunoassays back from more widespread adoption and approval for clinical chemistry workflows.

Repeatability and reproducibility are different but not mutually exclusive parameters of an experimental method workflow. Repeatability is a measure of the similarity of results performed on the same day with the same methods and batch reagents – expressed as standard deviation. Reproducibility is a measure of the similarity of results performed on different reagents preparations using exclusive experimental setups – expressed as coefficient of variation or %CV. Both are measures of precision and each are tests of a methods robustness, reliability, and competence to produce an actionable result. ELISAs and other complex immunoassays have traditionally been challenged by these measures, partly due to the multiple steps requiring pipetting and liquid exchange.

New technologies are focused on automation of the method to allow not only better precision, but higher-throughput and multiplexing abilities.

• Companies specializing in testing kits, antibodies, and reagents have increased the precision and quality of results generated from ELISAs and other immunoassays.
• Automation has increased performance further by minimizing manual pipetting and liquid exchange errors.
• Reactions and detection can be now be performed in 96 or 384 plates, interrogating multiple analytes in each well.
• The detection signals are now collected and analyzed by digital algorithms enabling high-throughput multiplexed processing with high accuracy and precision.

These multiplex immunoassay technologies may be a prelude of what is to come in more routine and widespread clinical diagnostics.

Microfluidics

Another trend that is gaining momentum is the use of microfluidic technologies for clinical applications. Such areas primarily involve point of care diagnostics, although a growing number of companies are focused in the areas of design fabrication for custom applications as well.

Microfluidics, as a technology, address major pain points in the typical diagnostic workflow.

• Increases in sensor or detector sensitivity means that smaller volumes are required, allowing cost savings in materials and waste disposal.
• Increased analytical performance equates to savings in time and operator costs.
• Miniaturization of testing chambers translates to smaller space requirements, making point of care applications feasible and advantageous.

These benefits have been harnessed in immunoassay applications including ELISA where reagents use and time-to-result are critical. Applications where traditional lateral flow devices are common are now being enhanced by microfluidics as well. Molecular detection by techniques such as isothermal assay is now better realized by multi-channel and modular optical features.

Sustainability

An area that is often overlooked but is becoming more and more important in lab operations is the concept of sustainability. Reagent and consumables usage have traditionally been closely linked with liquid handling methods and applications. Advances in multiplexing and microfluidics and other refinements have helped reduce waste and foster the practice of sustainability. Certain consumables, however, are a necessity for automated liquid handling systems and other high-throughput devices – and as such, no obvious way around their use exists.

An emerging trend is focusing on minimizing the throughput of consumables such as pipetting tips by washing and regenerating their useful life. Plastic pipette tips are traditionally disposed of after a single use and incinerated with biohazard waste. It is clear, well beyond the lab, that single use plastics present a problem for our environment, not to mention the expenses associated with production and disposal.

Although a tall order, a successful platform for liquid handling tips recycling and reuse may involve several key metrics.

• The washing system must be efficient and able to accommodate tips in a number of formats specific to various liquid handling platforms from which they come.
• The washing system must have sufficient quality control and precision to ensure that each batch of tips exhibit the same performance as an entire lot needed for a given application.
• Moreover, extensive validation must be performed on tip types, applications, and user labs, in order to confirm that indeed the recycled tips perform as well as new, across the full spectrum of laboratory operations and locations.

Summary

The three trends above are moving the automated liquid handling industry forward. The application of these advancements to better and more refined clinical diagnostics is a reality that is approaching with accelerating speed. It will continue to be interesting to see what new technologies appear along the way towards the future of clinical lab medicine.

Updated July 2022

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