EP3851191A1 - Plunger lift pipette, data processing apparatus and system and method for operating a plunger-lift pipette - Google Patents

Abstract

The invention relates to a method, a computer program and a system for operating a hand-held, computer-controlled piston-operated pipette and a corresponding piston-operated pipette, as well as a data processing device interacting with this, whereby a sequence of pre-wetting of the pipette tip enables precise pipetting of liquids with a higher vapor pressure than water is made possible.

Description

The invention relates to a method, a computer program and a system for operating a hand-held, computer-controlled piston-operated pipette and a corresponding piston-operated pipette and a data processing device that interacts with this.

Such hand-held piston pipettes are commonly used in medical, biological, biochemical, chemical and other laboratories. They are used in the laboratory to transport and transfer fluid samples with small volumes, especially for precise dosing of the samples. With piston-operated pipettes, for example, liquid samples are sucked into pipette tips by means of negative pressure, stored there, and released again at the destination. An electrically operated hand-held piston-operated pipette can often be controlled by at least one pipetting program in order to carry out at least one type of pipetting process in an automated manner.

Pipetting devices in the general sense include, for example, hand-held pipettes and dispensers. Hand-held pipettes are designed for one-handed use by human users. But there are also laboratory machines with robotized gripping arms, the gripping tools of which simulate the activities of a human hand for operating a hand-held pipette and which are set up for handling and operating a hand-held pipette.

A pipette is understood to mean a device in which a sample to be pipetted can be sucked into a pipetting container connected to the pipette by means of a movement device which is assigned to the device and which can in particular have a piston. In the case of a piston-operated pipette, also referred to as an "air cushion pipette", the piston is assigned to the device. Between the pipetted sample arranged in the pipette tip and the end of the piston there is an air cushion which is expanded when the sample is taken up in the pipette tip, causing the sample to be vacuumed is sucked into the pipette tip. A dispenser is understood to mean a device in which a volume to be pipetted can be sucked into a pipetting container connected to the dispenser by means of a movement device, which can in particular have a piston, the movement device being at least partially assigned to the pipetting container, for example by the piston is arranged in the pipetting container. With the dispenser, the end of the piston is very close to the sample to be pipetted or in contact with it, which is why the dispenser is also known as a positive displacement pipette.

In the case of a pipetting device, the amount of sample released by a single actuation can correspond to the amount of sample sucked into the device. However, it can also be provided that a quantity of sample received corresponding to several delivery quantities is delivered again in steps. In addition, a distinction is made between single-channel pipetting devices and multi-channel pipetting devices, with single-channel pipetting devices containing only a single delivery / receiving channel and multi-channel pipetting devices containing multiple delivery / receiving channels, which in particular allow the parallel delivery or receiving of multiple samples. Pipetting devices can in particular be hand-operated, i.e. imply a driving of the movement device generated by the user, and / or can in particular be operated electronically. Even in the case of manual operation of the movement device, a pipetting device can be an electric pipetting device, for example by electrically setting the current output volume or at least one other operating parameter. The pipetting devices described in the context of the present invention are hand-held, computer-controlled piston-operated pipettes with an electric piston drive, also referred to as hand-held, electronic pipettes.

An example of a hand-held, electronic pipette of the prior art is the Eppendorf Xplorer® and Xplorer® plus from Eppendorf AG, Germany, Hamburg; Examples of hand-held, electronic dispensers are the Multipette® E3 and Multipette® E3x from Eppendorf AG, Germany, Hamburg.

Electric pipetting devices offer numerous advantages over non-electric ones Pipetting devices, since a large number of functions can be implemented in a simple manner. In particular, in the case of electrical pipetting devices, the implementation of specific, program-controlled pipetting processes can be simplified by automating or partially automating them. Typical operating parameters for controlling such pipetting processes by means of appropriate pipetting programs relate to the volume when sucking in or dispensing liquid, its sequence and repetitions, and possibly its time parameters in the time distribution of these processes. An electrical pipetting device can be designed to be operated in one operating mode or several operating modes. An operating mode can provide that a set with one or more operating parameters of the pipetting device, which influence or control a pipetting process of the pipetting device, is automatically queried, set and / or applied.

In practice, piston-operated pipettes are often used to pipette aqueous samples, in which water forms the basis of the liquid sample. After the aqueous liquid has been sucked into the pipette tip, there is an essentially constant air pressure in the air space (the area of the so-called “air cushion”) between the inside of the pipette tip and the end of the piston. Changes in air pressure can occur in particular when the temperature of the liquid changes, since the vapor pressure is temperature-dependent. Unless otherwise stated, a room temperature condition is assumed below. In this case, the vapor pressure of water and thus of the pipetted sample is also essentially constant immediately after the aqueous sample has been sucked into the pipette tip. The vapor pressure is the pressure that is established when a vapor with the associated liquid phase is in thermodynamic equilibrium in a closed system.

In contrast to aqueous samples, the problem with liquids with a higher vapor pressure arises that the sample drips off after being drawn into the pipette tip for the first time. This is due to the fact that with these liquids the vapor in the mentioned air space with the liquid sucked in is not yet in thermodynamic equilibrium after the first sucking in, rather the pressure rises after the first suction during a period of time until the thermodynamic equilibrium is reached only at a significantly higher vapor pressure than with water, which leads to the liquid sample dripping off.

In the experiments on which the invention is based, liquids with a higher vapor pressure were divided into three classes which differ in their vapor pressure. The solvent ethanol falls into the first class, methanol into the second class, and acetone into the third class. All three classes are liquids that have a significantly higher vapor pressure than water, with acetone having the highest vapor pressure.

The liquids mentioned with a higher vapor pressure are more difficult to pipette than water because of the problems of dripping mentioned.

The invention is based on the object of specifying a method, a system and a computer program or a piston-operated pipette with which liquids with a higher vapor pressure than water can be conveniently and precisely pipetted.

The invention solves this problem by the method according to claim 1, the hand-held piston-operated pipette according to claim 12, the system according to claim 15, the computer program according to claim 16 and the data processing device according to claim 17. Preferred embodiments are in particular the subjects of the dependent claims.

The method according to the invention is a method for operating a hand-held, computer-controlled piston-operated pipette, which is used for the computer-controlled implementation of a pipetting process with a liquid sample, in particular for automatic pre-wetting of the inside of a pipette tip, which is arranged on the working cone of the piston-operated pipette, having the computer-controlled steps: • Providing a function n_vb (x) which specifies a number n_vb of one or more pre-wetting steps as a function of a variable x characterizing the pipetting process, • detecting the at least one parameter value of the variable x characterizing the pipetting process; • Determining the number n_vb of pre-wetting steps assigned to the variable x from the function n_vb (x); • Execution of a pre-wetting step or a sequence of the number n_vb of several pre-wetting steps, where n_vb> 0 and where a pre-wetting step in each case includes that an electrically driven piston movement is carried out by the piston-operated pipette in order to take up a sample volume in the pipette tip, and then an inverse piston movement is carried out is to dispense the sample volume contained in the pipette tip at least partially or completely again from the pipette tip.

The function n_vb (x) assigns a value n_vb to the values of a one- or multi-dimensional variable x. The value range of the function n_vb (x) contains at least two different values.

The variable x can be one-dimensional, i.e. contain only one parameter, e.g. a volume. The variable x can be multidimensional, i.e. it can contain several parameters, e.g. type of liquid and volume. The possibility of selecting different values n_vb as a function of the variable x means that an individual number of pre-wetting steps can be selected for different pipetting conditions. In this way, it is possible in particular to minimize the time expenditure resulting from the pre-wetting steps, which is necessary in order to be able to carry out the desired pipetting processes precisely with a liquid having a higher vapor pressure than water, even without the liquid dripping off. As a yardstick for a temporal optimization, for example, the number of pre-wetting steps should prevent dripping of the pipette tip filled with the liquid for a period of time Δt measured from the complete absorption of the sample into the pipette tip.

The invention is based on the observation that the time until the thermodynamic equilibrium that can be set by the pre-wetting steps is reached in the space between the liquid and the piston in the case of a liquid taken up in the pipette tip can depend on a wide variety of factors. If you take this into account factors or parameters that are easy to determine, one obtains an optimal pipetting strategy for the liquid sample in question.

When a pipette tip is prewetted, the liquid interface that is formed in the loaded pipette tip between the liquid and the volume of air above the liquid is increased. After the liquid has been sucked into the pipette tip, this liquid interface is initially formed by the meniscus, the surface of which, if the pipette tip is held vertically, will have a slightly larger area than the circular cross-section at the level of the meniscus through the conical or cylindrical interior of the vessel formed by the pipette tip Pipette tip. If the liquid is almost completely dispensed from the pipette tip, a liquid film remains on the inside of the pipette tip, which - as a first approximation - corresponds to the previously maximally wetted inner surface of the pipette tip. Since this wetting area is significantly larger than the meniscus, the liquid that evaporates per time is also correspondingly larger - until the liquid film has completely evaporated. The vapor pressure required in the air volume for equilibrium can develop more quickly as a result. An equilibrium between gravitational force and the negative pressure present in the air space is immediately present after the necessary pre-wetting steps have been carried out, so that dripping is prevented at least for the test period Δt under consideration. Corresponding measurements that can be carried out easily and reproducibly for all liquids, pipette tips and device types of piston-operated pipettes are explained in connection with the figures.

The function n_vb (x) preferably optimizes a number n_vb of one or more pre-wetting steps depending on a variable x characterizing the pipetting process in such a way that the air pressure achieved in the air cushion between the liquid sample and the stationary piston of the piston-operated pipette by means of the pre-wetting is sufficiently constant, to prevent the sample to be sucked into the pipette tip during the pipetting process from dripping out. The air pressure is assumed to be sufficiently constant in particular if dripping is prevented under standard conditions for a period of time Δt. Time periods suitable for manual pipetting are, for example, preferably in each case, Δt = 10 seconds, Δt = 15 s, Δt = 20 s, Δt = 25 s, Δt = 30 s, Δt = 40 s, Δt = 50 s, Δt = 60 s. The standard conditions include a situation at room temperature, the piston-operated pipette should be stored vibration-free and motionless from the time the volume V of the sample to be pipetted is drawn into the pipette tip, e.g. by placing the piston-operated pipette in one Pipette stand, with the pipette tip in particular being mounted vertically, that is to say parallel to the force of gravity. The time from the end of aspiration until a first drop of liquid drips off the lower end of the pipette tip is recorded.

The type of liquid, i.e. in particular the vapor pressure of the liquid to be specified under standard conditions, turned out to be an important factor in determining the number n_vb of pre-wetting. For ethanol this vapor pressure is 58 hPa, for methanol 129 hPa and for acetone 246 hPa. The liquid type can be described by a parameter ID_LM which chemically identifies the main liquid component of the liquid sample to be pipetted.

In the case of mixtures of liquids with a known vapor pressure, the mixing ratio can be used as a factor in determining the number n_vb of pre-wetting. If a liquid is used that does not tend to drip off, in particular due to a low vapor pressure, e.g. water, as a diluent for a liquid with a higher vapor pressure, then the dilution can also be used as a factor in determining the number n_vb of pre-wetting, in particular by naming the Amount, volume or weight fraction of the diluent contained in the liquid sample to be pipetted, identifiable by a parameter ID_VM.

Another important factor in determining the number n_vb of pre-wetting turned out to be the filling level in a pipette tip, based on the nominal volume (nominal maximum filling) of the pipette tip, which can be viewed, for example, at 100%, 50 and 10% of the nominal volume. Similarly, the volume V taken up in the pipette tip during a pipetting process is an important factor in determining the number n_vb of pre-wetting.

The device type of the piston-operated pipette turned out to be a further important factor in determining the number n_vb of pre-wetting. This can be explained, among other things, by the fact that the volume of the air space between the outlet of a working cone and the piston of the piston-operated pipette differs from device to device. Said air space makes a significant contribution to the entire air space between the liquid and the end of the piston, in which a vapor pressure has to be established in order to form an equilibrium. A parameter ID_GT which identifies the device type of the piston-operated pipette performing the pipetting process can therefore also be used as a factor or parameter. Equivalent to such a parameter is a set of known piston-operated pipettes, each of which has a specific device type with a specific nominal volume (e.g. the pipette set: 10 µl pipette, 100 µl pipette, 300 µl pipette, 1000 µl pipette, 1200 µl pipette) Pipette, 5 ml pipette, 10 ml pipette), the use of a parameter V_nom, which contains the nominal volume of the pipette and thus uniquely identifies the pipette.

The type of pipette tip is also a parameter that can be used to determine the number n_vb of pre-wetting. On the one hand, the wettability can vary due to the material of the pipette tip. On the other hand, the pipette tips have different inner surface sizes, which determine the setting of the vapor pressure, as well as varying nominal volumes and air space volumes above the liquid. A parameter ID_ST which identifies the pipette tip used in the pipetting process can therefore also be used as a factor or parameter.

Another parameter that can be used to determine the number n_vb of pre-wetting can be the speed v_K at which the piston of the piston-stroke pipette is moved when the at least one pre-wetting step is carried out. In this context, however, it is particularly preferred to use the maximum speed that can be set for a specific piston-operated pipette, since this directly determines the period of time required to carry out the at least one pre-wetting step, which is to be minimized.

Since the vapor pressure, and thus also the number n_vb of pre-wetting also of Environmental parameters p_u depends, this can also be used as a factor. A relevant parameter for determining the number n_vb of pre-wetting is the temperature T of the vicinity of the piston-operated pipette or the liquid sample to be pipetted during the pipetting process, and / or an air pressure or vapor pressure P of the environment of the piston-operated pipette that is present for the pipetting process.

The function n_vb (x) assigns a value n_vb to the values of a one- or multi-dimensional variable x. The value range of the function n_vb (x) contains at least two different values. A function n_vb (x) which is valid in practice for a wide variety of pipetting situations contains a large number of different assignments of a value n_vb to the components or parameters of a multidimensional variable x, the value range then contains a large number of different values of the number n_vb. The assignments can be in the form of a data assignment table, which can represent the function n_vb (x). The function can contain the data assignment table in order to assign a number n_vb to the variable x.

• einen den Hauptflüssigkeitsbestandteil der zu pipettierenden flüssigen Probe chemisch identifizierenden Parameter ID_LM,
• einen den Gerätetyp der Kolbenhubpipette identifizierenden Parameter ID_GT oder V_nom,
• mindestens ein oder zwei unterschiedliche Füllstände FV_nom, oder genau zwei oder genau drei unterschiedliche Füllstände FV_nom der zur Kolbenhubpipette passenden Pipettenspitze, insbesondere Füllstände FV_nom bei 10%, 50% und/oder 100% des Nennvolumens.

Diese Kombination x=(ID_LM; ID_GT oder V_nom; FV_nom) erwies sich in der Praxis als geeignet, um für fast alle Pipettiersituationen geeignete Anzahl n_vb von Vorbenutzungen anzugeben. Insbesondere lässt sich für zu pipettierende bzw. in die Pipettenspitze aufzunehmende Flüssigkeitsprobenvolumina, die nicht den Werten FV_nom entsprechen, die geeignete Anzahl aus einem Algorithmus bzw. einer Näherungsgleichung angeben, die sich aus den Wertepaaren (n_vb; FV_nom) ermitteln lässt. Als eine geeignete Näherungsgleichung erwies sich hierbei insbesondere eine Gerade oder eine Kombination aus zwei Geradenabschnitten. Dies wird nachfolgend noch erläutert.The variable x preferably contains the following combination of parameters:

• a parameter ID_LM that chemically identifies the main liquid component of the liquid sample to be pipetted,
• a parameter ID_GT or V_nom that identifies the device type of the piston-operated pipette,
• at least one or two different filling levels FV_nom, or exactly two or exactly three different filling levels FV_nom of the pipette tip matching the piston-operated pipette, in particular filling levels FV_nom at 10%, 50% and / or 100% of the nominal volume.

This combination x = (ID_LM; ID_GT or V_nom; FV_nom) turned out to be suitable in practice for specifying a suitable number n_vb of prior uses for almost all pipetting situations. In particular, for liquid sample volumes to be pipetted or taken up in the pipette tip that do not correspond to the values FV_nom, the suitable number can be specified from an algorithm or an approximation equation that can be determined from the value pairs (n_vb; FV_nom). As a suitable one The approximation equation turned out to be a straight line or a combination of two straight line sections. This is explained below.

In practice, it has also proven to be advantageous, even if this is not technically imperative, to limit the number n_vb of pre-wetting steps to a maximum number n_max. The number n_max = 99, n_max = 50 proves to be particularly useful; n_max = 20; n_max = 10. With such values, you can work optimally with most liquids, with a focus either on maximizing the dripping security or on minimizing the time span used for pre-wetting (time optimization). If a sample to be pipetted does not drip under certain parameters of x, the function n_vb (x) assigns the value N_vb = 0 (zero) to the corresponding parameters x in practice; no pre-wetting is necessary there. The invention includes that the function n_vb (x) contains at least one value n_vb> 0, which is assigned to at least one variable, that is to say parameter combination x.

Due to the desired time optimization, it also turned out to be advantageous to use the maximum speed v_K_max of the piston movement. In the experiments on which the invention is based, the maximum piston speed for piston-operated pipettes with a nominal volume of V_nom = 10 µl, 100 µl, 300 µl, 1000 µl was v_K_max = V_nom / 1.8 s, with V_nom = 1200 µl, v_K_max = V_nom / 2 , 0 s, at V_nom = 5 ml, 10 ml is v_K_max = 5.2 s.

The function n_vb (x) can also partially or completely contain at least one calculation algorithm or be represented by this in order to assign the number n_vb to the variable x. Such an algorithmic assignment is particularly suitable for determining further values by interpolation or extrapolation on the basis of known, since experimentally determined, value assignments of n_vb (x). For example, some of the parameters of the variable x can be determined experimentally, and for a selected parameter xi, that is a component of x, the algorithm can be used to make an assignment that assigns the desired values n_vb (xi) to a variation of xi. In particular, in the case of a device type that has been determined in particular beforehand a piston-operated pipette, in particular with a previously determined pipette tip type and in particular a previously determined liquid type, a series of value assignments n_vb (xi) can be made via an algorithm, with xi in particular being the volume V to be pipetted during a planned pipetting process, in particular to be aspirated into the pipette tip.

In a preferred embodiment, the variable x contains the parameter value V of the volume of the pipetting volume V to be aspirated into the pipette tip during the pipetting process or is formed by this parameter value V, the function n_vb (V), in particular depending on the solvent of the sample aspirated during the pipetting process, is described as a linear relationship between n_vb and V, i.e. n_vb = a ^∗ V + b. Where a and b are real numbers. The range of the pipettable volumes V is preferably divided into two sections, in each of which a characteristic parameter set a, b applies, so that in the first section V1 to V2 of possible volumes the relationship n_vb = a1 ^* V + b1 and in the second section V2 up to V3 of possible volumes the relation n_vb = a2 ^∗ V + b2 holds, and in particular a1 <> a2 and b1 <> b2. In experiments, this representation leads to a sufficiently precise description of the optimal number n_vb of pre-wetting as a function of the pipetting volume V.

The method according to the invention is in particular a method for automatically pre-wetting the inside of a pipette tip which is arranged on the working cone of the piston-operated pipette, having the computer-controlled steps mentioned in the claim. Since the pre-wetting causes the implementation of a precise pipetting step, the method according to the invention is in particular a method for carrying out a computer-controlled pipetting process by means of a hand-held, computer-controlled piston-stroke pipette, having the steps of the method according to the invention for automatic pre-wetting, and having the step that, following the execution of the Sequence of the number n (n> = 1) of one or more pre-wetting steps, the following computer-controlled step is carried out automatically: aspirating a sample volume V of the liquid sample into the pipette tip and in particular holding this sample volume V of the liquid sample in the pipette tip, in particular for an indefinite period of time or a certain period of time Δt.

The provision of the function n_vb (x), which specifies a number n_vb of one or more pre-wetting steps as a function of a variable x characterizing the pipetting process, can be implemented in different ways in terms of device technology:
An external data processing device is preferably provided, which in particular has a data interface device, in particular a user interface device (for example a touchscreen) and in particular an electronic control device. One piston stroke pipette or several piston stroke pipettes can be provided, with each piston stroke pipette being able to have an electronic control device. The control devices of the external data processing device and the piston-operated pipette can each be set up to exchange data with one another via a wired or preferably wireless data connection.

The data connection can in particular be a remote data connection which preferably uses a radio network, in particular WLAN. For this purpose, the external data processing device and the piston-operated pipette preferably each have a radio device for data exchange, in particular a radio module, e.g. a WLAN network adapter.

The control device of the external data processing device is preferably set up to use the data interface device, in particular the user interface device, to record at least one or all of the named parameters of the variable x, in particular one or more of the parameters ID_LM, ID_VM, ID_GT, ID_ST, v_K, pu, T or P The data interface device can be set up to acquire some or all of the parameters mentioned via the data connection, in particular remote data connection, for example WLAN, with another external data processing device, which can be a PC, smartphone or tablet computer, for example. The control device and / or the data interface device can be set up to retrieve parameters, in particular those of the variables x, partially or all from a data memory, in particular to record a data memory of the external data processing device.

The user interface device preferably includes at least one input device, e.g. a keyboard, a computer mouse device, a microphone for voice control, a camera for gesture detection, and / or a touchscreen, via which a user can make inputs on the external data processing device, and preferably includes at least one output device, e.g. a screen, loudspeaker through which the user can receive information from the external data processing device. A touch screen can serve as a combined input and output device. The variable x can, however, also be recorded by the control device of the external data processing device via a further data connection between the external data processing device and a further external data processing device, in particular a computer, tablet computer or smartphone.

The control device of the external data processing device or the external data processing device and / or the piston-operated pipette or its control device preferably has a data memory on which the function n_vb (x) is or can be stored.

The control device of the external data processing device or the control device of the piston-operated pipette is preferably set up or programmed to determine the value of the number n_vb of prewetting steps from the at least one or all of the named parameters of the variable x using the function n_vb (x). The external data processing device can in particular use control software, in particular stored in a data memory, which controls the functions of the external data processing device, in particular the function for detecting the variable x, the function for determining the value n_vb from the function n_vb (x) and / or the function of exchanging data with a piston-operated pipette, in particular to transmit at least one value, preferably the previously determined value n_vb, to the piston-operated pipette or its control device.

In particular, if the function n_vb (x) is stored in the piston-operated pipette and is evaluated by the control device of the piston-operated pipette, the external data processing device is not essential for carrying out the invention. It is possible that the control device of the external data processing device is set up or programmed to detect the parameters of the variables x all or in part by means of the data interface device and to transmit them to the control device of the piston-operated pipette by means of the data connection. The control device of the piston-operated pipette can be set up to use the parameters of the variable x recorded in this way to determine the assigned value n_vb from the function n_vb (x), with the function n_vb (x) in particular being able to be stored in a data memory of the piston-operated pipette.

The control device of the external data processing device is preferably set up or programmed to receive a response signal, in particular response data, from the control device of the piston-operated pipette after the transfer of at least the value n_vb or the transfer of parameters of the variable x to the control device of the piston-operated pipette. By receiving this response signal, the control device of the external data processing device is preferably set up to register the successful transmission of the parameters sent and / or to register a transmission error. Information containing the success or failure of the transmission can be output to the user via the user interface device of the external data processing device,

The control device of the piston-operated pipette is preferably set up or programmed to transmit a response signal, in particular response data, from the control device of the external data processing device to the control device of the external data processing device after the acquisition of at least the value n_vb or the acquisition of parameters of the variable x.

The control device of the at least one piston-operated pipette preferably detects the value n_vb via the data connection and, in particular, saves it temporarily in a data memory of the piston-operated pipette. It is also preferred that the control device the at least one piston stroke pipette in addition to the value n_vb via the data link also records further values, in particular the liquid volume V to be pipetted in the desired pipetting process and / or a speed v_K of the piston speed (s) to be used during the pipetting process, and saves these values, in particular temporarily in a data memory of the piston-operated pipette. In this way, all values that are required for the automated implementation of a one-step or multi-step pipetting process can be transmitted from the external data processing device to the piston-operated pipette, which in particular uses these values to carry out the named pipetting process.

The external data processing device is preferably a handheld computer. The external data processing device is not part of the hand-held piston-operated pipette and is therefore referred to as "external". It preferably has a housing in which the further components of the external data processing device are contained, in particular: the control device, a data interface device, in particular a user interface device, in particular a screen, in particular a touchscreen, or an input device for user input, a data interface, in particular a radio device for data exchange, and / or a power supply connection and / or a battery.

The hand-held piston-operated pipette according to the invention for the computer-controlled execution of a pipetting process with a liquid sample has: an electronic control device, a piston chamber and a piston movable therein, an electric piston drive for moving the piston, in particular an electric motor, a working cone to which a pipette tip can be attached . The control device is set up to control the piston drive and to execute a pipetting program that comprises the following steps: Execution of a sequence of the number n_vb of one or more pre-wetting steps, wherein a pre-wetting step in each case includes in particular that the piston-operated pipette performs an electrically driven piston movement is to take up a sample volume in the pipette tip, and then an inverse piston movement is carried out in order to dispense the sample volume at least partially or completely from the pipette tip, • following the at least one pre-wetting step: carrying out a pipetting process, including the aspiration of a sample volume V of the liquid sample into the pipette tip and in particular holding this sample volume V of the liquid sample in the pipette tip, in particular for an indefinite period of time or a certain period of time Δt.

The control device of the hand-held piston-operated pipette according to the invention is preferably set up to receive the value of the pipetting volume V to be aspirated into the pipette tip during the pipetting process and / or the value n_vb via a data connection from an external data processing device, and which has a data memory in which the value V and / or the value n_vb can be stored.

The piston-stroke pipette can be a single-channel pipette or a multi-channel pipette. Single-channel pipettes contain only a single dispensing / receiving channel or only a single working cone, and multi-channel pipettes contain several dispensing / receiving channels or working cones, which in particular allow the parallel dispensing or receiving of several samples.

The invention also relates to a system for the automatic pre-wetting of the inside of a pipette tip, which is arranged on the working cone of a hand-held, computer-controlled piston-operated pipette, which is used for the computer-controlled implementation of a pipetting process with a liquid sample, having at least one hand-held piston-operated pipette according to the invention, an external data processing device that has a User interface device (e.g. touch screen) and an electronic control device, the control devices of the external data processing device and the piston-operated pipette being set up to exchange data with one another via a data connection, preferably a remote data connection, e.g. WLAN, the control device of the external data processing device being set up by means of the User interface device to detect a variable x, in particular the parameter value V of the volume of the in the pipetting process in the pipette space itze to be aspirated pipetting volume V, a parameter ID_LM identifying the solvent of the liquid sample to be pipetted, a device type for the pipetting process parameters ID_GT or V_nom identifying the piston-stroke pipette performing the pipette tip type, and / or in particular a parameter ID_ST that identifies the pipette tip type of the pipette tip used in the pipetting process, the system in particular having at least one data memory containing the function n_vb (x), via which the control device selects the at least one or all of the named parameters of the variable x determine the value of the number n_vb of pre-wetting steps, and the system is set up to use the function n_vb (x) to determine the value of the number n_vb of pre-wetting steps from the at least one or all of the named parameters of the variable x to determine, wherein the control device of the at least one piston stroke pipette is set up to detect the number n_vb of pre-wetting steps, in particular via a data connection with the external data processing device. The piston-operated pipette is preferably a device operated independently of the mains and in particular has a rechargeable battery as an energy source for the electrical functions of the piston-operated pipette.

• eine Datenschnittstelleneinrichtung, insbesondere Benutzerschnittstelleneinrichtung, z.B. Touchscreen, und
• eine elektronische Steuereinrichtung,
• wobei die Steuereinrichtung des Datenverarbeitungsgeräts dazu eingerichtet, insbesondere programmiert ist - also ein dazu geeignetes Computerprogramm aufweist, insbesondere das erfindungsgemäße Computerprogramm - über eine Datenverbindung, z.B. eine Datenfernverbindung, z.B. WLAN, Daten mit der Steuereinrichtung einer Kolbenhubpipette auszutauschen, insbesondere der erfindungsgemäßen Kolbenhubpipette, die der computergesteuerten Durchführung eines Pipettiervorgangs mit einer flüssigen Probe dient,
• wobei die Steuereinrichtung des Datenverarbeitungsgeräts eingerichtet ist, insbesondere programmiert ist, mittels der Datenschnittstelleneinrichtung eine Variable x zu erfassen, insbesondere den Parameterwert V des Volumens des in dem Pipettiervorgang in die Pipettenspitze anzusaugenden Pipettiervolumens V, einen das Lösungsmittel der zu pipettierenden flüssigen Probe identifizierenden Parameter ID_LM, einen den Gerätetyp der den Pipettiervorgang durchführenden Kolbenhubpipette identifizierenden Parameter ID_GT, und/oder einen den Pipettenspitzentyp der im Pipettiervorgang verwendeten Pipettenspitze identifizierenden Parameter ID_ST, und
• wobei die Steuereinrichtung des Datenverarbeitungsgeräts dazu eingerichtet ist, insbesondere programmiert ist, aus dem mindestens einen oder allen der genannten Parameter der Variablen x den Wert der Anzahl n_vb der Vorbenetzungsschritte zu ermitteln und für die Datenverarbeitung durch die Steuereinrichtung der Kolbenhubpipette bereitszustellen und/oder über die Datenverbindung an die Kolbenhubpipette zu übertragen. Das Datenverarbeitungsgerät, insbesondere dessen Steuereinrichtung, kann einen Datenspeicher aufweisen, der die Funktion n_vb(x) enthält, über die die Steuereinrichtung aus dem mindestens einen oder allen der genannten Parameter der Variablen x den Wert der Anzahl n_vb der Vorbenetzungsschritte ermittelt. Dieser Datenspeicher kann aber auch auf einem weiteren Datenverarbeitungsgerät außerhalb des Datenverarbeitungsgeräts angeordnet sein, und die Parameter der Variablen x bzw. der daraus ermittelte Wert n_vb können über die Datenschnittstelleneinrichtung, die z.B. eine drahtlose oder drahtgebundene Datenverbindung realisieren kann, zwischen der Steuereinrichtung des Datenverarbeitungsgeräts und dem weiteren Datenverarbeitungsgerät ausgetauscht werden.

The invention also relates to a data processing device, which is in particular said external data processing device, having:

• a data interface device, in particular a user interface device, for example a touchscreen, and
• an electronic control device,
• wherein the control device of the data processing device is set up, in particular programmed - that is, has a suitable computer program, in particular the computer program according to the invention - to exchange data with the control device of a piston-operated pipette, in particular the piston-operated pipette according to the invention, via a data connection, e.g. a remote data connection, e.g. WLAN computer-controlled execution of a pipetting process with a liquid sample is used,
• wherein the control device of the data processing device is set up, in particular programmed, to detect a variable x by means of the data interface device, in particular the parameter value V of the volume of the pipetting volume V to be aspirated into the pipette tip during the pipetting process, a parameter ID_LM identifying the solvent of the liquid sample to be pipetted, one the device type the parameter ID_GT identifying the piston stroke pipette performing the pipetting process, and / or a parameter ID_ST identifying the pipette tip type of the pipette tip used in the pipetting process, and
• The control device of the data processing device is set up, in particular programmed, to determine the value of the number n_vb of prewetting steps from the at least one or all of the named parameters of the variable x and to make it available for data processing by the control device of the piston-operated pipette and / or via the data connection to be transferred to the piston-operated pipette. The data processing device, in particular its control device, can have a data memory which contains the function n_vb (x), via which the control device determines the value of the number n_vb of the prewetting steps from the at least one or all of the named parameters of the variable x. This data memory can, however, also be arranged on another data processing device outside the data processing device, and the parameters of the variable x or the value n_vb determined therefrom can be between the control device of the data processing device and the data interface device, which can, for example, implement a wireless or wired data connection further data processing device are exchanged.

The invention also relates to a computer program, in particular a computer program for operating a hand-held, computer-controlled piston-operated pipette, which is used for the computer-controlled implementation of a pipetting process with a liquid sample, in particular for automatic pre-wetting of the inside of a pipette tip that is arranged on the working cone of the piston-operated pipette, the computer program Includes commands which, when the computer program is executed by the central processor, of at least one electrical control device of the piston-operated pipette or an external data processing device, cause this central processor to carry out the following steps: • Detecting the at least one parameter value of the variable x characterizing the pipetting process; • Access to a data memory in which a function n_vb (x) is stored which specifies a number n_vb of one or more pre-wetting steps as a function of a variable x characterizing the pipetting process, • Determination of the variable x assigned to the variable x Number n_vb of pre-wetting steps from the function n_vb (x); Providing at least the value n_vb so that it can be used by the control device of a piston-operated pipette in order to carry out at least one pre-wetting step of the number n_vb; optional: • Execution of a pre-wetting step or a sequence of the number n_vb of several pre-wetting steps, wherein a pre-wetting step in each case includes that an electrically driven piston movement is carried out by the piston stroke pipette in order to take up a sample volume in the pipette tip, and then an inverse piston movement is carried out in order to dispensing the sample volume at least partially or completely from the pipette tip; • optional: following the at least one pre-wetting step: carrying out a pipetting process, including sucking a sample volume V of the liquid sample into the pipette tip and in particular holding this sample volume V of the liquid sample in the pipette tip, in particular for an indefinite period of time or a specific one Time span Δt of in particular 30 seconds.

The piston-operated pipette or an external data processing device preferably have a storage device. This preferably has a data memory, in particular a hardware data memory, in particular a non-volatile data memory, in particular an EPROM or FLASH memory. It can also have a volatile data memory.

The hand-held piston-operated pipette according to the invention, in particular its control device, is preferably designed to use at least one operating parameter for carrying out at least one pipetting process, which is used to control a pipetting process.

The electrical control device of the piston-operated pipette or of an external data processing device, also referred to for short as a control device or control device, preferably has a data processing device which, in particular, has at least one central processor (CPU). The control device preferably has a microcontroller. The control device preferably has at least one memory device or a data memory for storing data, in particular of operating parameters and / or one or more computer programs or computer program codes.

The control device preferably contains at least one control software or a control program that uses this at least one operating parameter to automatically carry out at least one function of the pipetting process or a part of the pipetting process or the pipetting process, in particular to carry out the at least one pre-wetting step, in particular using the for the Pipetting process selected parameter n_vb, which forms an operating parameter. The control software or the control program is executed in particular by the data processing device of the control device, in particular by a CPU of the data processing device. The control software or the control program is in particular stored in a memory device of the device. This memory device is preferably a non-volatile memory.

The hand-held piston-operated pipette according to the invention is preferably designed to be used to carry out at least one pipetting process in accordance with at least one operating mode (ID_OM) of the pipetting device. In an operating mode, one operating parameter (operating parameter set) is preferably provided in each case, which is used to control a pipetting process that is carried out in this operating mode.

A pipetting process typically provides that, according to a pipetting program, a certain amount of sample is taken from a start container into a pipetting container connected to the piston-operated pipette, in particular a pipette tip, and / or dispensed into a target container, in particular dispensed in a metered manner. A pipetting process can preferably be controlled by at least one, preferably several, or a set of operating parameters with which the named pipetting process or a function or component thereof can be influenced in the desired manner.

Operating parameters for controlling a pipetting process relate or quantify preferably the volume to be pipetted, during the step of aspirating the sample into a pipetting container connected to the piston-operated pipette or during the step of dispensing the sample from this pipetting container, possibly the sequence and repetitions of these steps, and possibly the time Parameters in the temporal distribution of these processes, in particular also the change in such processes over time, in particular the speed and / or acceleration of the aspiration or dispensing of the sample.

These operating parameters are preferably at least partially and preferably completely selected and / or entered by the user, in particular via the at least one operating element of the user interface device of a piston-operated pipette or an external data processing device.

The pipetting process is preferably clearly defined by the operating parameter set. This operating parameter set is preferably at least partially and preferably completely selected and / or entered by the user, in particular via the operating device of the piston-operated pipette or the external data processing device.

However, it is possible that a pipetting process is not clearly defined by the operating parameter set. It is also possible and preferred that at least one operating parameter is not specified by the user, but is specified, for example, by the pipetting device, in that it is stored there, for example, as previously known. The pipetting device can be designed to automatically determine at least one operating parameter.

The piston-operated pipette or an external data processing device can have a sensor device, for example a sensor for detecting an environmental parameter, in particular the temperature, the humidity or the pressure, the motor current used for the piston drive of the piston-operated pipette. The motor current can in particular be used to determine the viscosity of the pipetted liquid, and thus to identify the liquid or to determine ID_LM. The sensor device can also be designed to carry out a measurement with which the type of a pipetting container connected to the pipetting device, in particular the maximum filling volume of the pipetting container, in particular a pipette tip, can be determined. The piston-operated pipette or an external data processing device can be designed to automatically determine at least one operating parameter, in particular a parameter used to determine the variable x, as a function of the measured value of the sensor device. As a result, the optimization of the pipetting parameters required for precise pipetting can be further improved.

Operating modes and the operating parameters that are preferably assigned to them are described below, each of which is preferably provided for the pipetting device:
An operating parameter is preferably provided with which a pipetting volume to be pipetted is defined. An operating parameter can be provided with which a suction volume to be drawn in during a suction step is defined and / or an operating parameter can be provided with which a discharge volume to be dispensed during a dispensing step is defined.

Preferably, at least one operating parameter is provided with which the number of immediately or indirectly successive pipetting volumes is determined, preferably at least one operating parameter with which the number of suction steps and / or dispensing steps and, in each case, preferably also the respectively associated pipetting volumes associated pipetting speeds and / or accelerations, and / or the respective associated time intervals between the steps is determined.

One operating mode preferably relates to the "dispensing" (DIS) of a sample. Associated operating parameters are in each case preferably: the volume of the individual sample, relating to the pipetting volume during one of several dispensing steps; the number of delivery steps; the speed at which the sample (s) are picked up; the speed when submitting the sample (s). The dispensing function is particularly suitable for quickly filling a microtiter plate with a reagent liquid and can be used, for example, to carry out an ELISA.

One operating mode preferably relates to the "automatic dispensing" (ADS) of a sample. Associated operating parameters are in each case preferably: the volume of the individual sample, relating to the pipetting volume during one of several dispensing steps; the number of delivery steps; the duration of the time interval according to which the dispensing steps are automatically carried out one after the other at constant time intervals - the time interval can define these time intervals or, for example, the delay between the end and the start of successive dispensing steps; the speed at which the sample (s) are picked up; the speed at which the sample (s) are dispensed. This dispensing function is even more convenient for filling a microtiter plate, as the user does not have to repeatedly trigger a dispensing step by pressing a button, for example, but rather the dispensing is time-controlled after starting the automatic dispensing. Like any other operating program in an operating mode, automatic dispensing can take place on condition that the corresponding program takes place at least when an actuating element is operated continuously, e.g. when a key is continuously pressed. This is advantageous, for example, in the case of long dispensing series or reactions in which precise observation of a time window is required. The automatic dispensing function is even more convenient for filling a microtiter plate, as the user does not have to initiate a single dispensing step himself, but this is done automatically, which can be used, for example, to carry out an ELISA.

One operating mode preferably relates to the “pipetting” (pip) of a sample. Associated operating parameters are in each case preferably: the volume of the sample to be pipetted; the speed at which the sample is taken up; the speed at which the sample is dispensed.

One operating mode preferably relates to the “pipetting with subsequent mixing” (P / Mix) of a sample. Associated operating parameters are in each case preferably: the volume the sample to be aspirated and / or the sample to be dispensed; the mixing volume; the number of mixing cycles; the speed at which the sample is taken up; the speed at which the sample is dispensed. The "Pipetting with subsequent mixing" function is recommended, for example, for pipetting very small volumes. If a dosing volume <10 µL is selected, it is advisable to rinse this into the respective reaction liquid. This is possible by automatically starting a mixing movement after the liquid has been dispensed. The mixing volume and the mixing cycles are defined beforehand. One application for this operating mode is, for example, the delivery of a liquid that is more difficult to dose than water due to its physical properties, the residues of which in the pipetting container, in particular the pipette tip, are then rinsed with the aid of the liquid already provided from the pipetting container or the pipette tip. Another application would be the immediate mixing of the dispensed liquid with the supplied liquid. This operating mode is advantageous, for example, when adding DNA to a mixed PCR solution.

An operating mode preferably relates to the “multiple uptake” of a sample, also referred to as “reverse dispensing” or “ASP” for aspirating. Associated operating parameters are in each case preferably: the volume of the sample (s) to be aspirated; the number of samples; the speed when recording; the speed of delivery. The function is used for multiple uptake of a quantity of liquid and delivery of the total quantity. In this case, multiple filling of the pipetting container in one process is not provided. The speed is the same for all samples. In the embodiment, the following preferably happens: starting from the basic position, the pipetting device takes up a partial volume by actuating the first type of operating device. After the last partial volume has been taken up, the pipetting device preferably outputs a warning message, which must preferably be confirmed by the user actuating the second type of operating device. The next time the second type of operating device is actuated, the total volume is released again. For actuation of the first or second type, the operating device preferably has at least two operating buttons, one for inputting a “first type” operating signal to the control device and one for inputting a “second type” operating signal to the control device. The operating device can in particular have a rocker that is pivotable in particular about an axis perpendicular to the longitudinal axis of the pipetting device, between a first signal trigger position ("rocker up") for actuation of the first type and a second signal trigger position ("rocker down") for actuation of the second type.

An operating mode preferably relates to the “diluting” (Dil) of a sample, also referred to as “dilution”. Associated operating parameters are in each case preferably: the sample volume; the air bubble volume; the diluent volume; the speed of recording; the speed of delivery. The maximum diluent volume = nominal volume - (sample + air bubble)). This function is used to take up a sample and a diluent with separation by an air bubble and dispense the total amount. The speed is the same for all partial volumes. In the execution, the following preferably happens: starting from the basic position, the pipetting device first takes up the diluent volume, then the air bubble and finally the sample. Each recording is preferably triggered separately by actuating the operating device of the first type. Then the total amount is dispensed in one go.

One operating mode preferably relates to the “sequential dispensing” (SeqD) of samples. Associated operating parameters are in each case preferably: number of samples (preferably up to a fixed predetermined maximum number Nmax of preferably 5 <= Nmax <= 15, preferably Nmax = 10); Individual volume of the individual samples; Recording speed; Speed of delivery. This function is used for the sequential dispensing of Nmax freely selectable volumes; in this case, multiple filling of the pipetting container is preferably not provided. The speed is the same for all samples. The number of samples is preferably the leading parameter for entering the individual volumes. When entering the volumes, the pipette must always check whether the maximum volume of the pipetting devices is not exceeded; if necessary, a warning message is output. After all parameters have been entered, the pipetting device takes up the total volume after actuating the first type of operating device and decreases an individual volume after actuating the second type of operating device. All further processes preferably behave like normal dispensing.

One operating mode preferably relates to the “sequential pipetting” (SeqP) of samples. Associated operating parameters are in each case preferably: number of samples (preferably up to a fixed predetermined maximum number Nmax of preferably 5 <= Nmax <= 15, preferably Nmax = 10); Individual volume of the individual samples; Recording speed; Speed of delivery. This function is used to pipette a maximum of Nmax freely selectable volumes that are programmed before the start and their sequence is fixed. The speed is preferably the same for all samples in order to enable simple operation of this operating mode. However, the speed can also be set differently. The sequence of the function corresponds to the sequence of pipetting. The previously entered volumes are processed in the programmed sequence. After delivery, a decision is made by actuating an actuating element, e.g. pressing a button, whether the next sample should be taken or a "blowout" before the next, i.e. a complete, safe blowing out of the sample still contained in the pipetting container by means of an overstroke, and / or whether the pipetting container is to be changed.

One operating mode preferably relates to the "reverse pipetting" (rPip) of samples. Associated operating parameters are in each case preferably: the volume of the individual sample; the speed of recording; the speed of delivery; Activation of the counter. With this "rPip" function, more than the volume to be dosed is taken up. This is achieved in that the piston is moved down before the liquid is taken up, namely by actuation of the second type, ie, for example by pressing a button or "rocker down", to the lower position of a blowout, i.e. an overstroke of the piston, which over the position of the piston goes beyond a pipetting stroke. When the volume uptake starts, the pipetting device picks up the volume of the blowout and the set volume. In order to remove the play in the drive in the delivery direction, the pipetting device performs an additional stroke which is immediately delivered again. This is similar to dispensing, but preferably takes place with automatic delivery of the discard stroke at maximum speed.

In the execution of the "rPip" operating mode, the following preferably occurs: the The piston of the pipetting device automatically moves to the blowout and remains in the lower position. Secondly, the first type of operating device is actuated: the piston moves upwards by the blowout path and by the stroke for the pipetting volume. Thirdly, the second type of operating device is actuated: the piston moves down the stroke for the pipetting volume and stops before the blowout. Fourth, two actuations of the second type of operating device take place: the piston performs the blowout and remains in the lower position. As an alternative to "fourth", the first type of operating device is actuated: the piston moves up the pipetting stroke. The "rPip" mode is particularly suitable for pipetting plasma, sera and other liquids with a high protein content. The "Pipetting" mode is particularly suitable for aqueous solutions. The "rPip" mode is particularly suitable for solutions containing wetting agents, in order to minimize foam formation when dispensing into the target vessel. The liquid is absorbed in particular with an overstroke (blowout volume). The overstroke here typically does not belong to the delivery volume and is preferably not delivered into the target vessel. In particular, if the same sample is used again, the overstroke can remain in the tip. If a different liquid is used, the overstroke and / or preferably the pipetting container is preferably discarded.

A control program for carrying out the desired pipetting process is preferably controlled by an operating parameter set. The control program can each be in the form of electrical circuits of the control device and / or be in the form of an executable program code which is suitable for controlling a control device which can be controlled by a program code and is preferably programmable.

The piston-operated pipette or an external data processing device is preferably designed to automatically check the parameter values entered by the user and to compare them with a permitted range of the respective operating parameter. If the parameter value entered by the user is outside the permissible range, the entry is either not accepted or set to a default value, which can be, for example, the minimum value or the maximum value or the last value entered can.

The piston-operated pipette and / or an external data processing device is preferably operated independently of the mains. In particular, the respective device can be provided with a rechargeable voltage source, for example one or more batteries. For this case, the device can have a charging interface connected to the chargeable voltage source.

Pipette tips are, in particular, single-use products and are preferably made of plastic. Depending on the maximum volume of liquid required, different pipette tips are used with the piston-operated pipette. Typical nominal volumes of commercially available pipette tips are e.g. 10 µL, 20 µL, 100 µL, 200 µL, 300 µL, 1000 µL, 1250 µL, 2500 µL, 5 mL, 10 mL (µL: microliter; mL: milliliter). A pipette tip generally has a conical container which is elongated along a longitudinal axis and which has a liquid exchange opening at the lower end and which has a conical and tubular end section which is open at the top at the upper end. The liquid is sucked into the pipette tip via a negative pressure in the interior of the pipette tip. The interior of the pipette tip is in a pipetting position, also referred to as the plug-on position, in which the pipette tip is connected to the connecting section of the piston-operated pipette, usually by being pushed on, fluidically connected to the pipetting channel of the piston-operated pipette, which is electrically movable via a piston chamber in the shape of a hollow cylinder Cylinder piston of the piston stroke pipette with which negative / positive pressure is applied.

The invention relates to a method, a hand-held piston-operated pipette, a data processing device interacting therewith, a system and a computer program. The possible and preferred configurations of each of these objects result from the description of all configurations of the respective other objects, in particular configuration options for the hand-held piston-operated pipette result from the description of the method, the - in particular external - data processing device, the system and the computer program.

• Fig. 1 zeigt in einer perspektivischen Schrägansicht schematisch ein Ausführungsbeispiel einer erfindungsgemäßen Kolbenhubpipette.
• Fig. 2 zeigt in einer perspektivischen Schrägansicht schematisch ein Ausführungsbeispiel eines externen Datenverarbeitungsgeräts, das zur Implementierung des erfindungsgemäßen Verfahrens verwendbar ist.
• Fig. 3 zeigt in einer perspektivischen Schrägansicht schematisch ein Ausführungsbeispiel eines Systems, das zur Implementierung des erfindungsgemäßen Verfahrens verwendbar ist.
• Fig. 4 zeigt exemplarisch eine Anzeigenseite zur Erfassung von Benutzerparametern und Wiedergabe von Informationen, die im Display des externen Datenverarbeitungsgeräts aus Fig. 2 anzeigbar ist.
• Fig. 5 zeigt schematisch den Ablauf des erfindungsgemäßen Verfahrens in einem Ausführungsbeispiel.
• Fig. 6 zeigt ein Diagramm mit der algorithmischen Darstellung der Anzahl n_vb von Vorbenetzungsschritten in Abhängigkeit vom Volumen V, wobei diese Funktion v_vb(V) im erfindungsgemäßen Verfahren gemäß einem Ausführungsbeispiel verwendbar ist.

Further preferred refinements of the method according to the invention, the hand-held piston-operated pipette, the data processing device interacting therewith, the system and the computer program emerge from the following description of the exemplary embodiments in conjunction with the figures and their description. The same components of the exemplary embodiments are essentially identified by the same reference symbols, unless otherwise described or if the context does not indicate otherwise. Show it:

• Fig. 1 shows in a perspective oblique view schematically an embodiment of a piston stroke pipette according to the invention.
• Fig. 2 shows, in a perspective oblique view, schematically an exemplary embodiment of an external data processing device which can be used to implement the method according to the invention.
• Fig. 3 shows, in a perspective oblique view, schematically an exemplary embodiment of a system which can be used to implement the method according to the invention.
• Fig. 4 shows an example of a display page for capturing user parameters and reproducing information from the display of the external data processing device Fig. 2 can be displayed.
• Fig. 5 shows schematically the sequence of the method according to the invention in one embodiment.
• Fig. 6 shows a diagram with the algorithmic representation of the number n_vb of pre-wetting steps as a function of the volume V, this function v_vb (V) can be used in the method according to the invention according to an exemplary embodiment.

Fig. 1 shows the hand-held electric piston stroke pipette 1, the pipette 1, in a perspective view. In the case of the pipette 1, the stroke of the piston is electrically driven. The actuation of the stroke in the different operating modes of the pipette is carried out electrically controlled by an electrical control device 17 with a connected storage device 18, inside the pipette 1. The control device 17 can have a radio module in order to communicate with an external data processing device 2.1 (see FIG Fig. 2 ) carry out a data exchange.

The operating parameters and other settings of the pipette can be controlled by the user via the user interface device or operating device and the display of the pipette. Several electrically controlled pipetting programs are stored in the pipette, a pipetting program preferably being assigned to each operating mode. A pipetting program can be clearly defined by a set of operating parameters. Once set, the pipetting program can be triggered by the user and is started automatically by the pipette. The pipetting program includes, in particular, that the method 100 according to the invention for prewetting the pipette tip 10 is carried out. If the parameter ID_LM <> 0, at least one step for prewetting is carried out, if the parameter ID_LM = 0, no step for prewetting is carried out. Instead of the value 0, any other default value can also be agreed. The value ID_LM = 0 can in particular identify water as the main liquid component of the sample to be piped.

The pipette 1 has a base body 2, which has a lower shaft section 3 and an upper section 4, which in particular has the display 5 and operating elements. The shaft section 3 extends parallel to the longitudinal axis A of the pipetting device, while the upper section 4 is arranged inclined with respect to the axis A and extends parallel to the axis B. Due to the inclined arrangement of the upper section 4, the display 5 can be used particularly ergonomically.

The pipette 1 has a grip area 7 with the holding tab 6, which when the user holds the pipette 1 as intended is supported on the user's index finger, while the grip area 7 lies in the palm of the hand of the user. With The thumb can especially reach the ejection button 8, by pressing it downwards along the axis A, the spring-mounted ejection sleeve 9 is moved downwards and the pipette tip 10 is thrown off the connecting cone 11 of the pipetting device on which it is attached. The ejection mechanism can also be driven electronically. The pipette 1 has a metallic contact projection 19 on each of the side surfaces of the upper section 4, which is used to charge the integrated accumulator which forms the energy store of the electric pipette.

The operating device (12; 13; 14a; 14b) has a selection wheel 12, a rocker 13 and a first operating button 14a and a second operating button 14b.

The disk-like selection wheel 12 is rotatably mounted on the base body 2, in particular parallel to the essentially planar front side of the upper section 4. A device for detecting the position of the selection wheel 12 is provided, which in the present case has a Hall sensor with which the relative position of the selection wheel 12 with respect to the base body is measured without contact. The selection wheel 12 has a number of detents which correspond to the number of adjustable positions of the selection wheel. In particular, the locking is such that a marking 12a for designating the set position of the selection wheel 12 can be aligned with the marking 15, which is fixedly arranged on the base body 2 on the front side of the upper section 4.

The color display 5 serves as a central information element for the user. In particular, the various operating modes of the pipette 1 are displayed there and the parameter values of the operating parameters are displayed. In each of the two areas 5a and 5b, information is displayed that tells the user which function on the currently displayed display page is linked to the first control button 14a or the second control button 14b, if a function is also linked to it on the respective display page is. Each of the operating buttons is thus designed as an operating element with a variable function and, in combination with its displayed function, is referred to as a "softkey". This is explained below.

The pipetting device is preferably designed to switch between the various functions of a softkey when a specific operating mode of the pipette 1 is set. This can be achieved, for example, by double-clicking the softkey or pressing the softkey longer for a minimum period of, for example, 2 seconds.

For each operating mode of the pipette 1, a display page, which is shown on the display, is provided with an operating mode-specific layout. An advertisement page can also be provided for the definition of at least one pre-wetting step. If adjustable operating parameters or other changeable entries are provided on the display page, these can be marked using the rocker switch 13 and in particular selected using the control button 14a, in which case the control button 14a has the "selection" function and is in the display at position 5a Text "Choose" is displayed. The parameter values of an operating parameter are changed or a selection or an entry is changed by actuating the rocker switch 13.

The rocker 13 is arranged on the base body so as to be pivotable about a pivot axis arranged perpendicular to the longitudinal axis A. If the user presses the upper area 13a, a first function of the rocker 13 is activated; if the user presses the lower area 13b, a second function of the rocker 13 is activated. The rocker is mounted in such a way that no function is triggered if it is not actuated. The rocker 13 is used in particular in a manual operating mode of the pipette to suck the sample to be pipetted into the pipette tip 10 as long as the upper area 13a is pressed by the user and also serves to dispense the sample from the pipette tip 10 as long as the lower area 13b is used by the user is pressed.

The pipette 1 can be operated in various operating modes, which have already been explained in detail above. A first number of operating modes can be set directly using the selection dial 12, a second number of operating modes can be set using a display page labeled "Special" or "Spc" with several selectable entries, each entry describing an operating mode. Via the selection dial An operating mode can also be set in which the at least one pre-wetting step is defined, in particular n_vb or x is defined.

The pipette 1 has a memory device with a data memory in which suitable memory areas are provided for at least one operating parameter or parameter of the variable x and the value n_vb. In other embodiments of the pipette, the data memory can also contain the complete function function n_vb (x) or the data area relevant for the pipette with regard to the relevant parameter ID_GT.

Fig. 2 shows the external data processing device 21, which is a portable hand-held computer, with a touch screen 22, a power cable connection 23 for operating the computer 21 and a USB connection 24. The electrical control device 25 has a data processing device to execute a control program (operating system) that controls the functions of the computer 21, in particular the display of the display content, such as the display page in Fig. 4 , the data exchange with the pipette 1 via a radio module contained in the control device, a WLAN network adapter. The control device 25 has a data memory in which the function n_vb (x) is stored here. This is formed from a data assignment table consisting of data and data correlations, and at least one data algorithm in order to interpolate or extrapolate further assignments n_vb (x) from known assignments n_vb (x). The determination of the content of the function n_vb (x) is shown below as an example. The computer is set up to determine the parameters of the variable x through user input, to determine the assigned value n_vb from the parameter values of the variable x from the function n_vb (x), and the value n_vb to the extent that other parameters x serving as operating parameters are via the WLAN - Network adapter to transmit wirelessly to the pipette 1.

Fig. 3 shows the system 200, which the pipette 1 and the external data processing device 21 have, which exchange data via a radio link 201, 250 ′, 250 ″ or via a network 250, in particular via WLAN.

• 41 Informations- und Eingabefeld zur Eingabe des Parameters V
• 42 Informations- und Eingabefeld zur Eingabe des Parameters v_k
• 43 Informations- und Eingabefeld zur Eingabe des Parameters p betreffend eine weitere Eigenschaft eines Pipettiervorgangs
• 44 Informations- und Eingabefeld zur Eingabe des Parameters ID_OM zur Auswahl des Betriebsmodus bzw. Pipettiermodus der Pipette
• 45 Informations- und Eingabefeld zur Eingabe des Parameters ID_ST betreffend den Pipettenspitzentyp
• 46 Informations- und Eingabefeld zur Eingabe des Parameters ID_LM betreffend den im Pipettiervorgang verwendeten Flüssigkeitstyp der Probe
• 47 Anzeigebereich zur Anzeige insbesondere von dem in Abhängigkeit der anderen Parameter x ermittelten Anzahl n_vb
• 48 Eingabefeld zum Starten der Übertragung der Daten, insbesondere n_vb, an die mit dem Computer 21 in Datenverbindung stehende Pipette 1
• 49 Eingabefeld zum Abbrechen der Eingaben

Fig. 4 shows a display page 40 for display in the touchscreen display 22 of the portable computer 21, which is used as an input device for entering parameters of the variables x or operating parameters of the pipette 1:
Show in it:

• 41 Information and input field for entering the parameter V
• 42 Information and input field for entering the parameter v_k
• 43 Information and input field for entering the parameter p relating to another property of a pipetting process
• 44 Information and input field for entering the ID_OM parameter to select the operating mode or pipetting mode of the pipette
• 45 Information and input field for entering the ID_ST parameter relating to the type of pipette tip
• 46 Information and input field for entering the ID_LM parameter relating to the type of liquid in the sample used in the pipetting process
• 47 Display area for displaying, in particular, the number n_vb determined as a function of the other parameters x
• 48 input field for starting the transmission of the data, in particular n_vb, to the pipette 1 which is in data connection with the computer 21
• 49 Input field for canceling the entries

• Schritt 101: Bereitstellen einer Funktion n_vb(x) im Datenspeicher des externen Computers 21, die eine Anzahl n_vb von einem oder mehreren Vorbenetzungsschritten n_vb in Abhängigkeit von einer den Pipettiervorgang charakterisierenden Variablen x angibt.
• Schritt 102: Erfassen des mindestens einen Parameterwertes (V; ID_LM) der den Pipettiervorgang charakterisierenden Variablen x über den Touchscreen 22, an dem der Benutzer diese Werte eingibt bzw. auswählt;
• Schritt 103: Ermitteln der der Variablen x zugeordneten Anzahl n_vb von Vorbenetzungsschritten aus der Funktion n_vb(x) durch die Steuereinrichtung 25 des externen Computers 21; die Steuereinrichtung 25 weist einen WLAN-Netzwerkadapter aus und ist hier dazu eingerichtet, automatisch die in Reichweite der Funkverbindung gefundenen WLAN-Netzwerkadapter geeigneter Kolbenhubpipetten, insbesondere den der Kolbenhubpipette 1, zu finden, insbesondere deren Identifikationsparameter ID_GT zu bestimmen, insbesondere in Abhängigkeit von ID_GT und den vom Benutzer festgelegten Werten von x (V, ID_LM) den -oder die- zutreffenden Werte n_vb aus der Funktion n_vb(x) zu ermitteln, wobei beachtet wird, dass nur die zum Pipettieren des gewünschten Probenvolumens V geeigneten Pipetten berücksichtigt werden, eine Datenverbindung zu diesen gefundenen WLAN-Netzwerkadaptern herzustellen und insbesondere die zutreffenden Werte n_vb, insbesondere auch V und andere Parameter, wie beispielsweise in Fig. 4 beschrieben, in Abhängigkeit von ID_GT an die jeweils betreffende Kolbenhubpipette ID_GT zu übertragen, insbesondere an die Kolbenhubpipette 1. Der Computer 21 überträgt in diesem Fall somit automatisch an alle in Reichweite befindlichen Pipetten die gewünschten Parameter, ohne dass der Benutzer die Pipette bei der Bedienung des Computers 21 gesondert auswählen muss. Es werden am Computer 21 vorzugsweise alle für den gewünschten Pipettiervorgang erforderlichen Betriebsparameter der Pipette 1 ermittelt und an die Pipette übertragen, so dass der Benutzer die Eingabeeinrichtung der Pipette 1 nicht nutzen muss, um den Pipettiervorgang zuzüglich vorgeschalteten Vorbenetzungsschritten sofort zu starten.
• Schritt 104: nachdem der Benutzer den automatischen Pipettiervorgang an der Pipette 1 durch Knopfdruck bzw. Eingabe gestartet hat: Ausführen einer Sequenz der Anzahl n_vb von Vorbenetzungsschritten in der Pipette 1, die diesen Wert und insbesondere auch V vom Computer 21 über das WLAN erfasst hat, wobei n_vb > 0 und wobei ein Vorbenetzungsschritt jeweils beinhaltet, dass von der Kolbenhubpipette eine elektrisch getriebene Kolbenbewegung durchgeführt wird, um ein Probenvolumen der Flüssigkeit mit der ID_LM in die Pipettenspitze aufzunehmen, und anschließend eine inverse Kolbenbewegung durchgeführt wird, um das in der Pipettenspitze enthaltene Probenvolumen vollständig wieder abzugeben. Indem für das Ansaugen während der Vorbenetzungsschritte nur das Volumen V (und nicht das komplette Nennvolumen der Pipette bzw. Pipettenspitze) verwendet wird, wird sichergestellt, dass die entsprechende Flüssigkeitsmenge auch zur Verfügung steht. Mit Auswahl von V legt der Benutzer fest, dass diese Menge verfügbar ist.
• Schritt 105: Ansaugen des Volumens V der flüssigen Probe (ID_LM) in die Pipettenspitze 10 und Halten dieser Flüssigkeitsmenge V für eine geeignete Zeitspanne Δt in der Pipettenspitze 10, insbesondere um die Probe in ein Zielgefäß abzugeben bzw. schrittweise in mehrere Zielgefäße abzugeben, bzw. den jeweils gewünschten Pipettiervorgang durchzuführen.

Fig. 5 shows an embodiment of the method 100 according to the invention. The method 100 is used to operate a hand-held, computer-controlled piston-operated pipette 1, which is used for the computer-controlled implementation of a pipetting process with a liquid sample, in particular for automatic pre-wetting of the inside of a pipette tip 10, which is attached to the working cone 11 of the piston-operated pipette 1 is arranged, having the computer-controlled steps:

• Step 101: Providing a function n_vb (x) in the data memory of the external computer 21 which specifies a number n_vb of one or more pre-wetting steps n_vb as a function of a variable x characterizing the pipetting process.
• Step 102: Acquisition of the at least one parameter value (V; ID_LM) of the variables x characterizing the pipetting process via the touchscreen 22, on which the user enters or selects these values;
• Step 103: Determination of the number n_vb of pre-wetting steps assigned to the variable x from the function n_vb (x) by the control device 25 of the external computer 21; the control device 25 has a WLAN network adapter and is set up here to automatically find the WLAN network adapter of suitable piston-operated pipettes, in particular that of piston-operated pipette 1, found within range of the radio link, in particular to determine their identification parameters ID_GT, in particular as a function of ID_GT and the values of x (V, ID_LM) specified by the user to determine the -or the- applicable values n_vb from the function n_vb (x), whereby it is ensured that only the pipettes suitable for pipetting the desired sample volume V are taken into account, a data connection for these WLAN network adapters found and in particular the applicable values n_vb, in particular also V and other parameters, such as in Fig. 4 described, depending on ID_GT to be transferred to the respective piston stroke pipette ID_GT, in particular to the piston stroke pipette 1. In this case, the computer 21 automatically transfers the desired parameters to all pipettes within range without the user having to open the pipette when operating the Computers 21 must select separately. All operating parameters of the pipette 1 required for the desired pipetting process are preferably determined on the computer 21 and transmitted to the pipette so that the user does not have to use the input device of the pipette 1 to immediately start the pipetting process plus upstream pre-wetting steps.
• Step 104: after the user has started the automatic pipetting process on the pipette 1 by pressing a button or entering: Execution of a sequence of the number n_vb of pre-wetting steps in the pipette 1, which has recorded this value and in particular also V from the computer 21 via the WLAN, where n_vb> 0 and where a pre-wetting step in each case includes that an electrically driven piston movement is carried out by the piston stroke pipette in order to mix a sample volume of the liquid with the ID_LM in the pipette tip, and then an inverse piston movement is carried out in order to completely dispense the sample volume contained in the pipette tip. Since only the volume V (and not the complete nominal volume of the pipette or pipette tip) is used for aspiration during the pre-wetting steps, it is ensured that the corresponding amount of liquid is also available. By selecting V, the user specifies that this amount is available.
• Step 105: Sucking in the volume V of the liquid sample (ID_LM) into the pipette tip 10 and holding this amount of liquid V for a suitable period of time Δt in the pipette tip 10, in particular in order to dispense the sample into a target vessel or to dispense it gradually into several target vessels, or carry out the required pipetting process.

Fig. 6 shows an algorithmic function n_vb (V) in which the number n_vb of pre-wetting (here: “prewetting steps”) is specified as a function of the desired volume V. The function has a first straight line section which specifies the volume values V between 10% and 50% of the nominal volume V_nom of the relevant pipette (ID_GT) for the relevant liquid (ID_LM), and a second straight line section which the volume values V between 50% and 100 % of the nominal volume V_nom of the pipette in question (ID_GT) for the liquid in question (ID_LM). This interpolation of values n_vb (V) has proven to be suitable in practice to also determine the values n_vb (V) not previously determined experimentally with sufficient accuracy. The algorithmic function n_vb (V) and other similar functions are part of the function n_vb (x) or supplement it.

Determination of the function n vb (x)

The following procedure is suitable to determine the function n_vb (x).

• Dampfdruck der Flüssigkeit
• Volumen des Luftpolsters der verwendeten Pipette
• Prozentualer Füllstand der Pipettenspitze
• Geschwindigkeit der Vorbenetzungsschritte

In order to prevent the organic solvents from dripping out of the pipette tip 10, the pipette tips used were partially prewetted several times. It shows that the required number of pre-wetting steps (the pre-wetting time) of a pipette depends on various factors of the variable x:

• Vapor pressure of the liquid
• Volume of the air cushion of the pipette used
• Percentage fill level of the pipette tip
• Speed of the pre-wetting steps

In each case 100%, 50% and 10% of the nominal volume were tested with each volume variant of the piston-operated pipette Xplorer® plus, Eppendorf AG, Germany. The necessary number n_vb of pre-wetting steps was determined until the pipette showed no dripping behavior for δt = 30 seconds. This minimum number n_vb of pre-wetting steps was counted in order to calculate an algorithmic function that predicts how many steps are required to pipette a certain volume and a certain liquid. Gravimetric tests were also performed as a control.

Based on the data obtained, linear functions could be formed for all tested pipettes (fill level 10% -50% and 50% to 100%), which describes the relationship between the fill level FV_nom of the pipette tip and the number of pre-wetting steps n_vb. The resulting liquid classes can be used to pipette any type of liquid with a higher vapor pressure than water and in particular lower vapor pressure than 250 hPa using at least one pre-wetting step.

For the organic solvents ethanol, methanol and acetone, the minimum number of pre-wetting steps n_vb could be determined for the tested pipette variants. The data can be used to calculate the relationship between the filling level of the pipette tip and the number of pre-wetting steps. Three liquids in pure form were selected for investigation: Vapor pressure [hPa] Ethanol 58 Methanol 129 acetone 246

These liquids were tested with 100%, 50% and 10% of the nominal volume with each volume variant of the "Xplorer Plus" pipette. In order to be able to pipette these liquids, a certain number of pre-wetting steps must be carried out so that the liquid does not drip out of the pipette tip for at least 30 seconds (Δt).

This minimum number of pre-wetting steps was counted in order to calculate a function n_vb (V) which predicts how many steps are required to pipette a certain volume V and a certain liquid.

The smaller the selected volume V or FV_nom to be pipetted, the more pre-wetting steps have to be carried out. The duration of the pre-wetting phase increases accordingly.

In all pipettes with a nominal volume of more than 100 µl, with a setting of 10% of the nominal volume, the dripping of the liquids could not be prevented for more than 30 seconds even after 99 pre-wetting steps.

Between the pre-wetting steps considered, from 100% to 50% and from 50% to 10%, linear functions can be formed which, in a sufficient approximation, determine the sufficient pre-wetting steps for these areas. The axis intercept and gradient of the functions for all volume variants can be taken from the following evaluation. These functions can then be used to create the desired fluid classes.

Apparently there is no difference between single-channel and the corresponding multi-channel pipettes. For future tests to determine pre-wetting steps, it is likely that not all variants of a pipette have to be tested individually. Of different variants with the same air cushion volume only needs to be tested one at a time.

The higher the selected speed, the shorter the pre-wetting time. For this reason, speed level 8 is selected for all pre-wetting steps.

The tests were carried out with the Xplorer Plus® and with the volume variants mentioned in the evaluation. The "pipetting and mixing" mode was used for more than one pre-wetting step. This allows the user-related time between submission and submission to be reduced. The "Pipetting" mode was selected for fewer pre-wetting steps.

During the test, the time was stopped until the first drop came off the pipette tip. If the time was below Δt = 30 seconds, the pre-wetting steps were increased until this value was reached (up to a maximum of 99 steps). All results of this series of tests can be found in the evaluation.

Implementation process

If several liquids were tested, the one with the lowest vapor pressure was started. This enabled the tester to orientate himself on the previous one with regard to the pre-wetting steps when testing the next liquid. The results were entered in a table according to the following scheme: pipette Volume fraction Required pre-wetting steps Liquid / vapor pressure 100% 50% 10%

Setup of the experimental procedure: A charging stand was placed on an elevation so that the pipette including the pipette tip could be hung over the beaker filled with the liquid. A stopwatch was also provided. The entire test was carried out at speed "8". During the first run, the liquid was taken up at 100% of the nominal volume and, without a pre-wetting step, it was checked whether the pipette began to drip after 30 seconds. If this was not the case, the value "0" was entered. Otherwise, the pre-wetting steps were gradually increased until the time of 30 seconds was observed or until the maximum value of 99 pre-wetting steps was reached. The values were entered accordingly. This procedure was used accordingly at 50% and then at 10% of the nominal volume. In the first pass in each case, the number of pre-wetting steps from the previous volume fraction could be started. After pre-wetting, the pipette was hung on an elevated charging stand and the stopwatch was started.

100 µl Pipette Volumenanteil Benötigte Vorbenetzungsschritte Achsenabschnitt b Steigung a Ausgewähltes Volumen V Steps berechnet Ethanol 58 hPa 100 % 1 3 -0,02 100 1 50 % 2 10 % 4 4,5 -0,05 10 4 The linear functions can be determined as in the following example of the 100µl pipette: Calculation of the axis intercept 100% to 50%; and 50% to 10%: $$\mathrm{Pre-wetting\; steps\; calculated}:=\mathrm{pitch}\left(\mathrm{a}\right)*\mathrm{w}\ddot{\mathrm{u}}\mathrm{nsches\; volume}\left(\mathrm{V}\right)+\mathrm{<figure-callout\; id="100"\; label="Intercept\; b"\; filenames="imgf0004.png"\; state="\{\{state\}\}">Intercept</figure-callout>}\left(\mathrm{b}\right)\left(\mathrm{}\right)$$

100 µl pipette Volume fraction Required pre-wetting steps Intercept b Slope a Selected volume V Steps calculated Ethanol 58 hPa 100% 1 3 -0.02 100 1 50% 2 10% 4th 4.5 -0.05 10 4th

The second linear function was determined accordingly with the values from 50% to 10%. The calculated pre-wetting steps serve as a control. The intercept and slope are the required values.

Achsenabschnitt Steigung Ausgewähltes Volumen Schritte berechnet Volumenanteil Time 0 0 100 0 1 0,0 0 0 10 0 0,1 0 0 0 100 0 1 0,0 0 0 10 0 0,1 0 0 0 100 0 1 0,0 0 0 10 0 0,1 0 Achsenabschnitt Steigung Ausgewähltes Volumen Schritte berechnet Volumenanteil Time 3 -0,02 100 1 1 1,8 4,5 -0,05 10 4 0,1 0,72 26 -0,24 100 2 1 3,6 21,5 -0,15 10 20 0,1 3,6 16 -0,14 100 2 1 3,6 85,25 -1,525 10 70 0,1 12,6 Results of the test series for the 10µl pipette and the 100µl pipette of a pipette set in the form of a data assignment table of the function n_vb (x): pipette 10 µl Volume fraction [%] Steps required Time speed Speed time at 100% multiplier Ethanol 58 hPa 100 0 0 8th 1.8 1 50 0 0 8th 1.8 0.5 10 0 0 8th 1.8 0.1 Acetone 246 hPa 100 0 0 8th 1.8 1 50 0 0 8th 1.8 0.5 10 0 0 8th 1.8 0.1 Methanol 129 hPa 100 0 0 8th 1.8 1 50 0 0 8th 1.8 0.5 10 0 0 8th 1.8 0.1 100 µl Volume fraction [%] Steps required Time speed Speed time at 100% multiplier Ethanol 58 hPa 100 1 1.8 8th 1.8 1 50 2 1.8 8th 1.8 0.5 10 4th 0.72 8th 1.8 0.1 Acetone 246 hPa 100 2 3.6 8th 1.8 1 50 14th 12.6 8th 1.8 0.5 10 20th 3.6 8th 1.8 0.1 Methanol 129 hPa 100 2 3.6 8th 1.8 1 50 9 8.1 8th 1.8 0.5 10 70 12.6 8th 1.8 0.1 $$\mathrm{Axis\; section}+\mathrm{pitch}*\mathrm{Selected}\ddot{\mathrm{a}}\mathrm{half\; volume}=\mathrm{Calculated\; steps}$$

Intercept pitch Selected volume Steps calculated Volume fraction Time 0 0 100 0 1 0.0 0 0 10 0 0.1 0 0 0 100 0 1 0.0 0 0 10 0 0.1 0 0 0 100 0 1 0.0 0 0 10 0 0.1 0 Intercept pitch Selected volume Steps calculated Volume fraction Time 3 -0.02 100 1 1 1.8 4.5 -0.05 10 4th 0.1 0.72 26th -0.24 100 2 1 3.6 21.5 -0.15 10 20th 0.1 3.6 16 -0.14 100 2 1 3.6 85.25 -1.525 10 70 0.1 12.6

Claims (17)

Method (100) for operating a hand-held, computer-controlled piston-operated pipette (1), which is used for computer-controlled execution of a pipetting process with a liquid sample, in particular for automatic pre-wetting of the inside of a pipette tip (10) which is arranged on the working cone (11) of the piston-operated pipette, having the computerized steps: • Provision of a function n_vb (x) which specifies a number n_vb of one or more pre-wetting steps as a function of a variable x characterizing the pipetting process, (101) • Detecting the at least one parameter value of the variable x characterizing the pipetting process; (102) • Determination of the number n_vb of pre-wetting steps assigned to the variable x from the function n_vb (x); (103) • Execution of a sequence of the number n_vb of pre-wetting steps, (104)
where n_vb> 0 and where a pre-wetting step in each case includes that an electrically driven piston movement is carried out by the piston-operated pipette in order to take up a sample volume in the pipette tip, and then an inverse piston movement is carried out in order to at least partially or completely restore the sample volume contained in the pipette tip submit. Method according to claim 1, wherein the variable x contains the parameter value V of the volume of the pipetting volume V to be aspirated into the pipette tip in the pipetting process or is formed by this parameter value V. The method according to claim 1 or 2, wherein the variable x is at least one of Contains parameter values of the following parameters or is formed by them, or by parameters that can be determined from the following parameters: a parameter ID_LM that chemically identifies the main liquid component of the liquid sample to be pipetted, a parameter ID_VM that identifies the diluent contained in the liquid sample to be pipetted, a parameter ID_GT that identifies the device type of the piston-operated pipette performing the pipetting process, a parameter V_nom that identifies the device type of the piston-operated pipette performing the pipetting process via its nominal volume, a parameter ID_ST that identifies the pipette tip type of the pipette tip used in the pipetting process, a speed v_K of at least during this pipetting process a piston movement of the piston stroke pipette carried out in a pre-wetting step, a temperature T of the surroundings of the piston stroke pipe which is present for the pipetting process tte or the liquid sample to be pipetted in the pipetting process, an air pressure or vapor pressure P in the vicinity of the piston-operated pipette during the pipetting process. Method according to one of Claims 1 to 3, wherein the function n_vb (x) contains at least one calculation algorithm to assign the number n_vb to the variable x and / or contains a data assignment table to assign the number n_vb to the variable x. Method according to one of claims 1 to 4, wherein the function n_vb (x) optimizes a number n_vb of one or more pre-wetting steps depending on a variable x characterizing the pipetting process in such a way that the air cushion between the liquid sample and the immobile piston of the piston-operated pipette the air pressure achieved by means of the pre-wetting is sufficiently constant to prevent dripping of the sample to be sucked into the pipette tip during the pipetting process. Method according to one of Claims 1 to 5, the variable x being the parameter value V of the volume to be aspirated into the pipette tip in the pipetting process Pipetting volume V or is formed by this parameter value V, and the function n_vb (V), in particular as a function of the solvent of the sample sucked in during the pipetting process, is described as a linear relationship between n_vb and V, i.e. n_vb = a * V + b, a and b are real numbers, the range of the pipettable volumes V preferably being divided into two sections, in each of which a characteristic parameter set a, b applies, so that in the first section V1 to V2 of possible volumes the relationship n_vb = a1 * V + b1 and in the second section V2 to V3 of possible volumes the relationship n_vb = a2 * V + b2 applies, and in particular a1 <> a2 and b1 <> b2. A method for carrying out a computer-controlled pipetting process by means of a hand-held, computer-controlled piston-operated pipette, having the method according to one of the preceding claims, and having the step that, following the execution of the sequence of the number n of one or more pre-wetting steps, the following computer-controlled step is automatically carried out: Sucking in a sample volume V of the liquid sample into the pipette tip and in particular holding this sample volume V of the liquid sample in the pipette tip, in particular for an indefinite period of time or a certain period of time. (205) Method according to one of the preceding claims, wherein an external data processing device is provided which has a user interface device (e.g. touchscreen) and an electronic control device, and wherein the piston stroke pipette is provided or several piston stroke pipettes are provided, one piston stroke pipette each having an electronic control device, the Control devices of the external data processing device and the piston-operated pipette are set up to exchange data with one another via a data connection (e.g. a remote data connection, e.g. WLAN),
wherein the control device of the external data processing device is set up to use the user interface device to detect at least one or all of the named parameters of the variable x, in particular the parameter value V of the volume of the pipetting volume V to be sucked into the pipette tip during the pipetting process, a solvent of the liquid sample to be pipetted identifying parameter ID_LM, a parameter ID_GT identifying the device type of the piston-operated pipette performing the pipetting process, and / or a parameter ID_ST identifying the pipette tip type of the pipette tip used in the pipetting process. Method according to claim 8, wherein the control device of the external data processing device is set up to determine the value of the number n_vb of prewetting steps from the at least one or all of the named parameters of the variable x using the function n_vb (x). Method according to Claim 8 or 9, the external data processing device and / or the at least one piston-operated pipette having a data memory in which the function n_vb (x) is stored and / or the value n_vb can be stored. Method according to claim 10, wherein the control device of the at least one piston-operated pipette detects the value n_vb via the data connection and stores it in a data memory of the piston-operated pipette. Having a hand-held piston-operated pipette (1) for the computer-controlled implementation of a pipetting process with a liquid sample
an electronic control device,
a piston chamber and a piston movable therein,
an electric piston drive to move the piston,
a working cone to which a pipette tip can be attached,
wherein the control device is set up to control the piston drive and execute a pipetting program comprising the following steps: • Execution of a sequence of the number n_vb of one or more pre-wetting steps,
wherein a pre-wetting step in each case includes that an electrically driven piston movement is carried out by the piston stroke pipette in order to take up a sample volume in the pipette tip, and then an inverse piston movement is carried out in order to dispense the sample volume at least partially or completely from the pipette tip, • following the at least one pre-wetting step: carrying out a pipetting process, including sucking a sample volume V of the liquid sample into the pipette tip and in particular holding this sample volume V of the liquid sample in the pipette tip. Hand-held piston-operated pipette according to claim 12, the control device of which is set up to receive the value of the pipetting volume V to be aspirated into the pipette tip during the pipetting process and / or the value n_vb via a data connection from an external data processing device (21), and which has a data memory in which the value V and / or the value n_vb can be stored. Hand-held piston-operated pipette according to claim 12 or 13, which is a single-channel pipette or a multi-channel pipette. A system (200) for automatically pre-wetting the inside of a pipette tip, which is arranged on the working cone of a hand-held, computer-controlled piston-operated pipette, which is used for the computer-controlled implementation of a pipetting process with a liquid sample
at least one hand-held piston pipette (1) according to one of the claims 12 to 14,
an external data processing device (21) which has a data interface device and an electronic control device,
wherein the control devices of the external data processing device and the piston-operated pipette are set up to exchange data with one another via a data connection,
wherein the control device of the external data processing device is set up to detect a variable x by means of the data interface device, in particular the parameter value V of the volume of the pipetting volume V to be aspirated into the pipette tip during the pipetting process, a parameter ID_LM identifying the solvent of the liquid sample to be pipetted, and the device type the parameter ID_GT identifying the piston stroke pipette performing the pipetting process, and / or a parameter ID_ST identifying the pipette tip type of the pipette tip used in the pipetting process, and
the system is set up to determine the value of the number n_vb of the pre-wetting steps from the at least one or all of the named parameters of the variable x using a function n_vb (x),
wherein the control device of the at least one piston-operated pipette is set up to detect the number n_vb of pre-wetting steps via the data connection. Computer program, in particular for operating a hand-held, computer-controlled piston-operated pipette, which is used for the computer-controlled implementation of a pipetting process with a liquid sample, in particular for automatic pre-wetting of the inside of a pipette tip that is arranged on the working cone of the piston-operated pipette, the computer program including commands that are used during execution of the computer program by the central processor at least an electrical control device cause this central processor to carry out the following steps, • Detection of the at least one parameter value of the variable x characterizing the pipetting process; • Access to a data memory in which a function n_vb (x) is stored which specifies a number n_vb of one or more pre-wetting steps as a function of a variable x characterizing the pipetting process, • Determination of the number n_vb of pre-wetting steps assigned to the variable x from the function n_vb (x); • Provision of at least the value n_vb for data processing by the control device of the piston-operated pipette, in particular transmission of at least the value n_vb to the control device of the piston-operated pipette; • optional: execution of a pre-wetting step or a sequence of the number n_vb of several pre-wetting steps,
wherein a pre-wetting step in each case includes that an electrically driven piston movement is carried out by the piston stroke pipette in order to take up a sample volume into the pipette tip, and then an inverse piston movement is carried out in order to dispense the sample volume at least partially or completely from the pipette tip; Optional: following the at least one pre-wetting step: carrying out a pipetting process, including sucking a sample volume V of the liquid sample into the pipette tip and in particular holding this sample volume V of the liquid sample in the pipette tip, in particular for an indefinite period of time or a certain period of time in particular of at least 30 seconds. Data processing device, which is in particular said external data processing device, comprising: A data interface device, in particular a user interface device, and • an electronic control device, wherein the control device of the data processing device is set up to exchange data via a data connection with the control device of a piston-operated pipette, in particular the hand-held piston-operated pipette according to one of claims 12 to 14, which is used for the computer-controlled implementation of a pipetting process with a liquid sample,
wherein the control device of the data processing device is set up to detect at least one parameter of a variable x by means of the data interface device, and
The control device of the data processing device is set up to determine the value of the number n_vb of the pre-wetting steps from the at least one or all of the named parameters of the variable x and to provide the piston-stroke pipette for data processing by the control device and / or to the piston-stroke pipette via the data connection transfer.

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