PHARMA LAB · PL-03-010

Automated liquid handling: system selection and requirements

Choose automation around the actual workflow. Connect requirements, configuration and testing without relying on a plate-wide average alone.
Automated liquid handling platform with a transparent protective enclosure, multichannel head and plates on the deck.

An automated system can repeat a sequence very consistently even when it is unsuitable for the sample. Selection starts by asking which transfers, controls and records the system must provide in the actual laboratory, including situations where something does not go as planned.

The user requirements specification, or URS, turns that question into verifiable conditions. It is neither a catalogue of features nor a generic request for a “GMP-certified” instrument.

Define samples, liquids and the workflow

Describe matrices, viscosity, volatility, foaming, particles and analyte sensitivity. Specify actual minimum and maximum volumes, sample availability, aliquots, dilutions, mixing and destinations. A nominal transfer range is insufficient: the system must aspirate from the intended vessel without drawing air, leaving excessive residue or changing the preparation.

Map the path from sample identification to a usable result: loading, transfers, waiting periods, any reading step and unloading. Define sample numbers and variability, full or partial plates, allowable duration and manual interventions. Robotic movement time alone does not represent overall throughput. If stability limits sequence duration, this becomes a selection requirement.

Assess the complete installed configuration

Compare independent channels and fixed-pitch heads against the positions that must be reached. Identify tips, vessels, geometries, adapters, deck capacity, residual volumes and space for reagents and waste. Include the readers, mixers, sensors and interfaces actually needed. An accessory recognised by the software may still require the correct geometry definition and positioning.

The scope of ISO 23783-1:2022 considers the complete automated system with its essential components and installed tips. Selection therefore concerns the combination used. Assess cleaning access, spill handling and protection from moving parts; do not plan tests that require interlocks to be bypassed.

Define and control liquid classes

A liquid class is an identified set of parameters for handling a liquid in a particular configuration and volume range. It may include aspiration and dispensing speeds, delays, immersion depth, air gaps, contact mode and corrections. A name such as “water” does not establish suitability for a different matrix.

Primary research on gravimetric optimisation of a fixed-tip system demonstrates dependence on settings and the liquid studied; its values are not a transferable recipe. In your system, retain the class identifier and version, tip, range and rationale for changes. If surrogate liquids are used, document their representativeness. Changing a correction requires subsequent verification, not simply saving the file.

Examine channels, positions and contamination

Define the systematic error and dispersion compatible with the method. Assess channels, positions and sequence stages separately: an acceptable overall average can hide a problematic channel. Consider small volumes, low source levels, first and last dispenses and relevant waiting periods. Testing must address identified risks with justified replicates and criteria.

ISO 23783-2 covers volumetric measurement procedures; part 3 concerns data organisation, evaluation and reporting. A gravimetric or photometric measurement itself needs known conditions, references and limitations. The 2026 study by Reddi and colleagues addresses photometric verification in a specific configuration; it does not certify every platform.

For carryover between samples, design a representative sequence with suitable controls and enough sensitivity to detect an effect relevant to the analysis. Changing tips reduces one transfer pathway but does not exclude contamination from surfaces, splashes or handling.

Specify software, identity and records

Associate the sample, source vessel, destination position, method and script version. Establish who can create, modify, approve and execute programs, and how imported files, errors and partial results are handled. A “sequence completed” message does not demonstrate that every transfer was valid.

For relevant GMP activities, Annex 11 links validation and data controls to risk. Define access, retention, retrievability and audit trails for relevant changes, with appropriate review. Test interruptions and data restoration as well: having a backup does not demonstrate the ability to restore it. Assess other jurisdictions’ scope and requirements separately; do not infer them from the presence of a data port.

Connect URS, selection tests and qualification

The following original matrix is a starting point to complete with application-specific responsibilities and criteria. Each requirement needs a verifiable outcome before it can be considered met.

Concise URS: requirement, test scenario and evidence
RequirementRepresentative scenarioExpected evidence
Transfer small volumes in the intended matricesRange boundaries, selected liquids and tipsData by channel and volume, deviation, dispersion and measurement limitations
Handle partial platesOccupied and empty positions in authorised configurationsSource-to-destination map and absence of unintended transfers
Control carryoverA sample and control sequence that makes carryover detectableResults against the analytical criterion and test sensitivity
Recognise an incorrect loadA simulated error under safe, authorised conditionsDetection, blocking or documented handling according to the requirement
Manage an interruptionA controlled stop during a test sequenceComplete, incomplete and uncertain positions identifiable; justified restart
Retain configuration and dataScript revision and retrieval of an archived recordVersions, authorisations and reconstruction of the work performed

In the applicable GMP context, Annex 15 provides the qualification framework. Connect requirements with design, installation, functions and performance in intended use; approve deviations and conclusions. Supplier documents can contribute, but their coverage needs assessment. Volumetric calibration does not replace demonstration of the transferred analytical workflow.

Transfer the method and maintain a controlled state

Simulated case, without experimental results: a manual protocol is automated using smaller volumes and different matrices. The initial water test passes. Before release, matrix transfer, mixing, stability during waits, contamination and sample-position correspondence still need demonstration. Comparison with the manual method uses criteria defined before execution; a similar average is insufficient. One liquid class might suit only some samples.

Train operators in loading, initial checks, anomalies and restart limitations. Retain the executed version, configuration and interventions. After a failure, do not restart blindly: identify completed and uncertain transfers. Changes to tips, vessels, the head, software or scripts require impact assessment and relevant testing before return to use.

Explore channel consistency, programs and interruptions and tip compatibility, or return to the Liquid Handling & Sample Preparation hub.

For the related steps, see: GMP sample preparation: workflow, traceability and controls.

Sources and applicability

ISO 23783, parts 1–3:2022: official catalogue entries consulted, not full texts. Cited studies: specific findings without generalising their settings or intervals. EU GMP Annex 11, 2011 revision, and Annex 15, 2015: versions listed in the official index checked on 30 September 2026, within the relevant human medicinal product GMP context. The draft Annex 11 revision is not treated as an effective requirement.

Technical content for informed decisions; it does not replace the approved procedure, applicable requirements or the instrument manual.

Continue exploring