Precision and accuracy in liquid handling

Part 2: How to evaluate and optimise liquid handling performance in depth

A key process in laboratory automation is the handling of liquids and samples. The objective performance evaluation and optimisation of automated liquid handling systems is extremely important for laboratory technicians as well as manufacturers of liquid handling technology.

In the first part of the article, the difference between the performance parameters precision and accuracy and its significance was explained. The second part takes a closer look at these two performance indicators.

Expert mode: Evaluating precision and accuracy in intra-run, inter-run and tip-to-tip dimensions

To enable fast and effective identification of sources of error, manufacturers and operators of liquid handling systems need an even more systematic and differentiated assessment of performance parameters.

This can be achieved by breaking down liquid handling, for instance on microplates, into the following very basic processes:

Three possible subsets of a data set including L × M × N measurements:

1) One dispensing channel dispenses a run of N aliquots for the intra-run experiments.

2) One dispensing channel dispenses M runs of N individual volumes of liquid per run for the evaluation of inter-run performance.

3) L dispensing channels dispense one run each of N individual liquid volumes for tip-to-tip experiments.

The characterisation of the dispensing performance within the four levels (1) intra-run, (2) inter-run, (3) tip-to-tip and (4) load-to-load performance enables a systematic, detailed and above all differentiated analysis of precision, accuracy and possible sources of error. (1) Intra-run measurements primarily provide information about the basic precision and accuracy of a single dispensing channel of a liquid handler that dispenses aliquots in a continuous run. Errors incorporated by pause times or using different tips are excluded from this analysis. (2) Inter-run measurements reveal errors due to pause time effects and evaluate the reproducibility or stability of a system. The delay time between any two runs for the purpose of characterisation can be adjusted to the anticipated pause times of the respective application, ranging from a few seconds to hours or days. (3) Tip-to-tip measurements evaluate error sources due to variations in the dispensing channel (e.g. different cartridges, nozzle variations, tubing variances, different pressure levels for different dispensing channels, etc.). (4) Load-to-load measurements assess sources of error due to loading operations using, for example, a cartridge or a disposable tip.