EP3851191A1 - Procédé de fonctionnement d'une pipette à course de piston, pipette à course de piston, appareil et système de traitement des données - Google Patents

Procédé de fonctionnement d'une pipette à course de piston, pipette à course de piston, appareil et système de traitement des données Download PDF

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Publication number
EP3851191A1
EP3851191A1 EP20152459.2A EP20152459A EP3851191A1 EP 3851191 A1 EP3851191 A1 EP 3851191A1 EP 20152459 A EP20152459 A EP 20152459A EP 3851191 A1 EP3851191 A1 EP 3851191A1
Authority
EP
European Patent Office
Prior art keywords
pipette
piston
pipetting
operated
volume
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP20152459.2A
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German (de)
English (en)
Inventor
Benjamin Förthmann
Philipp Cloer
Jens Kleemann
Torsten Krauss
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eppendorf SE
Original Assignee
Eppendorf SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Eppendorf SE filed Critical Eppendorf SE
Priority to EP20152459.2A priority Critical patent/EP3851191A1/fr
Priority to CN202110042914.4A priority patent/CN113145193B/zh
Priority to JP2021004733A priority patent/JP7506612B2/ja
Priority to US17/151,073 priority patent/US20210252498A1/en
Publication of EP3851191A1 publication Critical patent/EP3851191A1/fr
Priority to JP2023001084A priority patent/JP2023029508A/ja
Pending legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • B01L3/0217—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids of the plunger pump type
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • B01L3/0217—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids of the plunger pump type
    • B01L3/0237—Details of electronic control, e.g. relating to user interface
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0615—Loss of fluid by dripping
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/023—Sending and receiving of information, e.g. using bluetooth
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/024—Storing results with means integrated into the container

Definitions

  • 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.
  • a piston-operated pipette also referred to as an "air cushion pipette”
  • the piston is assigned to the device.
  • 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.
  • 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.
  • the amount of sample released by a single actuation can correspond to the amount of sample sucked into the device.
  • a quantity of sample received corresponding to several delivery quantities is delivered again in steps.
  • 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.
  • 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.
  • 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.
  • piston-operated pipettes are often used to pipette aqueous samples, in which water forms the basis of the liquid sample.
  • air cushion the air space 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.
  • 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.
  • 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 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
  • 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.
  • the number of pre-wetting steps should prevent dripping of the pipette tip filled with the liquid for a period of time ⁇ t 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.
  • 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 ⁇ t.
  • 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.
  • 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.
  • 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.
  • n_vb of pre-wetting 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.
  • 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 ⁇ l pipette, 100 ⁇ l pipette, 300 ⁇ l pipette, 1000 ⁇ l pipette, 1200 ⁇ l 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.
  • 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.
  • the wettability can vary due to the material of the pipette tip.
  • 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.
  • v_K the speed at which the piston of the piston-stroke pipette is moved when the at least one pre-wetting step is carried out.
  • 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.
  • n_vb the number of pre-wetting steps
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 ⁇ t.
  • 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.
  • a data connection preferably a remote data connection
  • 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,
  • 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
  • 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.
  • ID_OM 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.
  • 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.
  • 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.
  • 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.
  • 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 ⁇ L 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.
  • 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.
  • the pipetting device takes up a partial volume by actuating the first type of operating device.
  • the pipetting 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.
  • the operating device 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.
  • 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.
  • the number of samples is preferably the leading parameter for entering the individual 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.
  • 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.
  • an actuating element e.g. pressing a button
  • 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.
  • 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.
  • the pipetting device picks up the volume of the blowout and the set volume.
  • 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.
  • the piston of the pipetting device automatically moves to the blowout and remains in the lower position.
  • the first type of operating device is actuated: the piston moves upwards by the blowout path and by the stroke for the pipetting volume.
  • the second type of operating device is actuated: the piston moves down the stroke for the pipetting volume and stops before the blowout.
  • two actuations of the second type of operating device take place: the piston performs the blowout and remains in the lower position.
  • 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.
  • the respective device can be provided with a rechargeable voltage source, for example one or more batteries.
  • 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 ⁇ L, 20 ⁇ L, 100 ⁇ L, 200 ⁇ L, 300 ⁇ L, 1000 ⁇ L, 1250 ⁇ L, 2500 ⁇ L, 5 mL, 10 mL ( ⁇ L: 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 shows the hand-held electric piston stroke pipette 1, the pipette 1, in a perspective view.
  • 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 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.
  • 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.
  • the various operating modes of the pipette 1 are displayed there and the parameter values of the operating parameters are displayed.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • n_vb 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
  • n_vb (V) 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.
  • 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.
  • 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.
  • 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.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Human Computer Interaction (AREA)
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EP20152459.2A 2020-01-17 2020-01-17 Procédé de fonctionnement d'une pipette à course de piston, pipette à course de piston, appareil et système de traitement des données Pending EP3851191A1 (fr)

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EP20152459.2A EP3851191A1 (fr) 2020-01-17 2020-01-17 Procédé de fonctionnement d'une pipette à course de piston, pipette à course de piston, appareil et système de traitement des données
CN202110042914.4A CN113145193B (zh) 2020-01-17 2021-01-13 用于运行活塞冲程吸移管的方法、活塞冲程吸移管、数据处理仪器和系统
JP2021004733A JP7506612B2 (ja) 2020-01-17 2021-01-15 ピストンストロークピペットを駆動する方法、ピストンストロークピペット、データ処理装置及びシステム
US17/151,073 US20210252498A1 (en) 2020-01-17 2021-01-15 Method for operating a piston-stroke pipette, piston-stroke pipette, data processing device and system
JP2023001084A JP2023029508A (ja) 2020-01-17 2023-01-06 ピストンストロークピペットを駆動する方法、ピストンストロークピペット、データ処理装置及びシステム

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EP20152459.2A EP3851191A1 (fr) 2020-01-17 2020-01-17 Procédé de fonctionnement d'une pipette à course de piston, pipette à course de piston, appareil et système de traitement des données

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CN113145193B (zh) 2022-12-13
US20210252498A1 (en) 2021-08-19

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