There are numerous medical, biological, chemical and pharmaceutical devices which involve the handling and use of liquids. Thus, for example, there are automated liquid handling systems for carrying out medical, biological, physical and chemical investigations or to carry out processes in these fields.
Nowadays, most of the automated liquid handling systems are so-called computer-controlled handling systems.
A typical computer-controlled handling system comprises a work area (worktable) for the placement of vessels, a motorized pipetting robot and a controller (usually a processor-based controller). The pipetting robot comprises at least one pipette for aspirating and dispensing liquid samples. Usually, each such pipette is connected by way of flow to a triggerable pump via an individual liquid conduit. The controller is connected by way of circuitry to the pipetting robot and/or the pumps. By implementing a sequential program which is executed in the controller, the pipetting robot can be moved to a specific position in order to execute a specific action there. Thus for example, a pipette can be lowered into a vessel in order to suck up a liquid there or to dispense a liquid.
The individual processes which are carried out in a handling system are mostly subdivided into handling groups. There are the following substeps for example: picking up a pipette, rinsing of a pipette, ejecting a pipette, aspirating, dispensing or mixing a liquid by using a pipette, and the dispensing of a liquid using a pipette.
One example for such a handling system of the present applicant is known on the market under the name of Freedom EVO®.
Such handling systems can be more or less complex. There is a tendency toward quasi standardisation of individual substeps and entire processes in order to better control and perform the individual processes.
The user is guided and supported by a graphic user interface when defining a process. In this connection, this is known as the preparation of a script. Such scripts can be implemented directly by a computer and can be carried out in the handling system, or they can be saved for later use. The substeps of an aspiration process and a dispensing process have mostly been determined in a rigid way as so-called standard actions.
A user interface (graphic user interface, GUI) is known for example from the U.S. Pat. No. 5,841,959, which allows the user to define individual standard actions which are subsequently carried out in a handling system. The user can determine as standard actions for example the aspiration and dispensing as well as the upward and downward movements of a pipette. This is done on the basis of icons which are brought on a screen to the desired chronological sequence. The U.S. Pat. No. 5,841,959 also provides the changing/adjustment of the parameters of individual standard actions.
There is a demand for better handling of repetitive sequences and also for better responding in a flexible way to different sample liquids and reagents and their different physical properties. This is especially relevant in connection with larger test series or examinations.
That is why in modern computer-controlled handling systems so-called liquid classes are used. A liquid class defines the parameters which are to be used on the part of the controller during pipetting of a specific liquid. The word liquid class is a designation which is used here, although other companies use other names for the definition of liquid-specific parameters in a handling system. Current liquid classes are partly subdivided into so-called subclasses. There can be for example a respective subclass for the pipetting volume ranges 3 to 5 μL, 15 to 500 μL, 500 to 1000 μL. Each of these subclasses typically has separate settings. This can lead to the consequence that in the first subclass for example for the range of 3 to 15 μL a different precision correction (a different calibration method) is used than in the next subclass with the range of 15 to 500 μL. In the case of a pipetting volume of 14.9 μL a different correction will be applied than in the case of a pipetting volume of 15.1 μL. This leads to inconsistencies for the precision corrections at the boundaries of the volume ranges.
In one liquid class, the parameters for handling a specific liquid can be defined, e.g. movement velocities of the syringes, accelerations, precision corrections, and/or the parameters for the detection of the liquid level (liquid level detection, LLD), e.g. sensitivity, immersion depth, and/or the parameters of the movements of the pipetting robot such as speeds, accelerations.
For minor adjustments to a liquid class, a given liquid class must be adjusted by the user, which is usually linked to the copying of an existing class, the changing and storing under a different name. This can lead to a confusingly large variety of slightly different liquid classes which are stored in a handling system. Confusion and problems can therefore not be excluded.
Each liquid which is to be used to handling system needs a respective liquid class and parameter in order to ensure the precision and reproducibility of the pipetting of this liquid.
Current handling systems are already supplied with a number of the standard defaults in form of principal liquid classes (e.g. for water, blood serum, ethanol etc) and with standard actions. A liquid class can have numerous parameters (partly more than 30 parameters) which can be adjusted by the user if required. Liquid classes of known handling systems allow a differentiation or selection according to the type of the used pipette such as coated steel cannulas, disposable tips of different volumes, and the pipetting volume to be pipetted. Furthermore, the parameters (such as the aspiration speed) for the aspiration and the parameters (such as the dispensing speed) for the dispensing can be defined within the liquid classes. Often it is possible to provide details on a calibration method which is relevant for the precision of the pipetting process.
Each of the liquid classes thus comprises a number of parameters which are all static, wherein other static parameters are predetermined for a first liquid volume of 3 to 15 μL than for a greater liquid volume 15 to 500 μL for example, as already mentioned above.
The predetermination of the individual parameters is partly very time-consuming, complex and susceptible to errors. There are many correlations and regularities which need to be considered. This concerns among other things the type of liquid, the liquid volume (known as pipetting volume) to be pipetted, the type of pipette, the overall configuration of the handling system and other influencing variables.
In the end, it is necessary that handling systems require a definition of the individual substeps in order to enable precise operation. The definition of the individual substeps however depends on aspects such as the properties of the liquid (viscosity, surface tension, density, vapour pressure), the current hardware configuration, the limits of said hardware, the requirements of the individual process step and ambient influences (pressure, temperature etc).