LU501825B1 - Method for setting a volume of liquid to be dispensed by using a function - Google Patents

Method for setting a volume of liquid to be dispensed by using a function Download PDF

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Publication number
LU501825B1
LU501825B1 LU501825A LU501825A LU501825B1 LU 501825 B1 LU501825 B1 LU 501825B1 LU 501825 A LU501825 A LU 501825A LU 501825 A LU501825 A LU 501825A LU 501825 B1 LU501825 B1 LU 501825B1
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LU
Luxembourg
Prior art keywords
liquid
volume
dispensed
receptacle
function
Prior art date
Application number
LU501825A
Other languages
German (de)
Inventor
Johannes Köppern
Original Assignee
Dispendix Gmbh
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 Dispendix Gmbh filed Critical Dispendix Gmbh
Priority to LU501825A priority Critical patent/LU501825B1/en
Application granted granted Critical
Publication of LU501825B1 publication Critical patent/LU501825B1/en

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01FMEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F11/00Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it
    • G01F11/28Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with stationary measuring chambers having constant volume during measurement
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05CAPPARATUS FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05C11/00Component parts, details or accessories not specifically provided for in groups B05C1/00 - B05C9/00
    • B05C11/10Storage, supply or control of liquid or other fluent material; Recovery of excess liquid or other fluent material
    • B05C11/1002Means for controlling supply, i.e. flow or pressure, of liquid or other fluent material to the applying apparatus, e.g. valves
    • B05C11/1007Means for controlling supply, i.e. flow or pressure, of liquid or other fluent material to the applying apparatus, e.g. valves responsive to condition of liquid or other fluent material
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01FMEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F13/00Apparatus for measuring by volume and delivering fluids or fluent solid materials, not provided for in the preceding groups
    • G01F13/006Apparatus for measuring by volume and delivering fluids or fluent solid materials, not provided for in the preceding groups measuring volume in function of time
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01FMEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F25/00Testing or calibration of apparatus for measuring volume, volume flow or liquid level or for metering by volume
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14Process control and prevention of errors
    • B01L2200/148Specific details about calibrations
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02Burettes; Pipettes
    • B01L3/021Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05CAPPARATUS FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05C5/00Apparatus in which liquid or other fluent material is projected, poured or allowed to flow on to the surface of the work
    • B05C5/02Apparatus in which liquid or other fluent material is projected, poured or allowed to flow on to the surface of the work the liquid or other fluent material being discharged through an outlet orifice by pressure, e.g. from an outlet device in contact or almost in contact, with the work

Abstract

The invention relates to method for setting a volume of liquid to be dispensed from a receptacle (2) by using a function for determining a volume of liquid to be dispensed, wherein the receptacle (2) comprises an inlet opening (3) for inletting liquid (1) into the receptacle (2) and an outlet opening (4) for dispensing liquid (1) from the receptacle (2), when a pressure is applied on the liquid (1), wherein the function is dependent on the liquid (1) to be dispensed and on a further liquid.

Description

10.04.2022 005A0017LU 1
LU501825
Method for setting a volume of liquid to be dispensed by using a function
The invention relates to a method for setting a volume of liquid to be dispensed by using a function for determining a volume of liquid to be dispensed from a receptacle. Additionally, the invention relates to a dispensing device for dispensing liquid, a computer program product, a computer readable data carrier and a data carrier signal.
Liquid handling is a fundamental process in many laboratories. In modern life science laboratories, high-throughput liquid handling is frequently needed for the purpose of efficiency. For liquid dispensing at the micro-, nano-, or even picolitre level, the surface adhesion is a fundamental factor that affects the performance. Basically, liquid-dispensing technologies have to overcome surface adhesion and dispense the droplet from the dispensing tool. When the volume is very small, gravity is not sufficient for dropping viscous samples. A variety of methods have been developed to overcome the problem by generating additional driving forces to dispense the droplet. In general, those methods can be classified into two categories: contact and noncontact dispensing, respectively.
In contact dispensing techniques, such as pipetting, a touch-off is necessary to complete the liquid dispensing. When the liquid attaches to a substrate, a drag-back action is done to overcome the surface tension between liquid and the dispensing tip, without which the liquid will not drop.
Contact dispensing is most popular for dispensing samples of small volume from nano- to microliter because of its simplicity, reliability, and low cost. However, reliable dispensing requires an accurate positioning system. Furthermore, special attention must be paid to hard contact, which may damage the dispenser tip by colliding with the container.
In noncontact dispensing techniques, the liquid is ejected from an orifice instead of using a contact between the liquid and the surface container. It reduces or eliminates some disadvantages of contact dispensing mentioned above. In particular, cross-contamination can be avoided. The most common approaches are based on the inkjet printing technology, thereby using different dispensing means, such as solenoid valves, piezoelectric dispensers, acoustic dispensers, electrostatic devices, etc..
Typically, liquid handling refers to small volume dispensing operations, however, at the micro-, nano- or picolitre level, the number of transferred samples can be huge. Under these conditions,
10.04.2022 005A0017LU 2
LU501825 liquid handling by hand can be very time-consuming and, in some cases, impractical.
Consequently, there is a strong demand for automated liquid handling systems. From the prior art, dispensing devices are known that comprise a dispensing head by means of which a pressure is applied on a liquid in a receptacle having an outlet opening. Due to the pressure a liquid is dispensed from the receptacle. There exists the need to secure that the dispensed liquid volume corresponds with a predetermined liquid volume independent of several parameters like the receptacle volume and/or the used liquid type. This is in particular important for liquids that are expensive and/or where the available liquid volume is small.
In known devices a function is used to determine the volume of liquid to be dispensed. However, the function is identified for a specific control variable value and/or a predetermined volume of liquid arranged in the receptacle from which the liquid shall be dispensed. Said function is usually determined in a training mode of the dispensing device. As the dispensing device can be operated under control variable values and/or different volumes of liquid arranged in the receptacle it would be necessary to identify several functions. With “identified” it is meant that in the training mode, in which the function is identified, the function is determined by using a specific liquid volume. This means, the function will provide accurate results if the volume of liquid that is arranged in the receptacle from which liquid shall be dispensed is identical to the specific liquid volume. However, in practice the volume of liquid that is arranged in the receptacle can differ from the specific liquid volume. Thus, the used function provides inaccurate results with respect to the volume of liquid to be dispensed so that several functions have to be identified.
Additionally, a sample of the liquid to be dispensed is needed for the training process, wherein the liquid sample cannot be used in the operation mode of the dispensing device. The costs of liquids are sometimes very high so that the liquid volume that is needed for performing the training process in order to identify all needed functions is not affordable and/or available.
The object of the invention is to provide a method by means of which the volume of liquid to be dispensed from a receptacle can be accurately set and in which the functions can be identified in an inexpensive manner.
This object is solved by a method for setting a volume of liquid to be dispensed from a receptacle by using a function for determining a volume of liquid to be dispensed, wherein the receptacle
10.04.2022 005A0017LU 3
LU501825 comprises an inlet opening for inletting liquid into the receptacle and an outlet opening for dispensing liquid from the receptacle, when a pressure is applied on the liquid, wherein the function is dependent on the liquid to be dispensed and on a further liquid.
Another object of the invention is to provide a dispensing system by means of which the volume of liquid to be dispensed from a receptacle can be accurately set and in which the functions can be identified in an inexpensive manner.
The object is solved by a dispensing device for dispensing liquid, wherein the dispensing device comprises a holder for holding a carrier comprising at least one receptacle, wherein the receptacle has an inlet opening for inletting liquid into the receptacle and an outlet opening for dispensing liquid from the receptacle, a dispensing head for providing a pressure on the receptacle and a control unit that is configured to set a volume of liquid to be dispensed from the receptacle by using a function for determining a volume of liquid to be dispensed, wherein the function comprises a first function part that is dependent on the liquid to be dispensed and a second function part that is dependent on a further liquid.
It has been recognized that it is possible to accurately set the volume of liquid to be dispensed if the function is not merely dependent on the liquid to be dispensed but also on a further liquid. The further liquid is cheaper than the liquid to be dispensed so that the function can be determined in an inexpensive manner. Using the further liquid in the training process results in that the needed volume of liquid to be dispensed for identifying the plurality of functions is lower than in cases in which merely the volume of liquid to be dispensed is used. Therefore, the costs for the training process are low and at the same time an accurate set of the volume of liquid to be dispensed is achieved.
Due to the automatic setting of the volume of liquid to be dispensed the method is also capable for high throughout dispensing. Another advantage of the invention is that the setting of the volume of liquid to be dispensed can be performed by components that are already present in known dispensing devices. Thus, there is no need to adapt the hardware of known dispensing devices.
The invention has the advantage that a plurality of functions can be determined and stored in the
10.04.2022 005A0017LU 4
LU501825 control unit of the dispensing device. In particular, functions that are identified for different volumes of liquid arranged in the receptacle from which the liquid is dispensed can be stored in the control
Unit and/or an electric or electronical memory. This enables that in operation of the dispensing device the function is selected that is assigned to the volume of liquid arranged in the receptacle.
Thus, it is secured that the dispensed volume of liquid corresponds or basically corresponds with the predetermined volume of liquid to be dispensed independent on the volume of liquid arranged in the receptacle and/or the control variable value. With “basically corresponds” it is meant that it is regarded as sufficient that the volume of dispensed liquid is within a predetermined range around the predetermined volume of liquid.
A function is understood as an assignment of values. This means, a value is assigned to another value because the values are interrelated. The function can be a mathematical equation, however, is not limited to the mathematical equation. For example, a table comprising values which are assigned to each other is also covered by a “function”. The output of the function can be a volume of liquid to be dispensed and/or the function can assign a control variable of the dispensing device to the volume of liquid to be dispensed.
The receptacle is capable of holding and releasing a liquid onto a target plate only when a defined pressure, in particular pressure pulse, is applied on top of the receptacle. In particular, the pressure is applied on the liquid arranged in the receptacle. When there is no pressure pulse applied on the receptacle, no liquid is released since capillary forces keep the liquid in the cavity. That means, no liquid is released due to the atmosphere pressure acting on the liquid.
A receptacle can be made out of polymers (e.g., polypropylene), metals (e.g., aluminum, copper) and/or glass. When a pressure, in particular pressure pulse is applied, on top of the receptacle a liquid droplet or liquid jet is released on a target carrier arranged below the receptacle. With “applying pressure on the liquid” it is meant that a pressure being different, in particular higher, than the atmospheric pressure is applied on the liquid.
The receptacle can be arranged in a through hole of a carrier, in particular a carrier element, in a releasable manner. That means, the connection between the receptacle and the carrier element can be disconnected without destroying the receptacle and/or the carrier element. Additionally, the receptacle can be inserted into the through hole or removed from the through hole without the use of any tools. Alternatively, the receptacle and the carrier element can be made in one form. In said
10.04.2022 005A0017LU
LU501825 embodiment each receptacle bottom has at least one outlet opening. Said embodiment can be used if the carrier has 384 or more receptacles.
The carrier can have one or more receptacles. Carriers that have more than one receptacle are also 5 indicated as multiwell plate. In particular, carriers are known that have 6, 12, 24, 48, 96, 384, 1536 and 3456 receptacles. The receptacles are arranged in a matrix structure on the carrier element, in particular in the through holes of the carrier element.
The outlet opening of the receptacle, in particular of the first receptacle and/or the second receptacle, can have a diameter between 60jum (micrometer) and 200um, in particular 100um. The dispensed liquid can be a liquid droplet or a liquid jet and/or have a volume of at least 10 nanoliters.
In particular, the dispensed liquid can have a volume in the range between 10 nanoliters to 100 nanoliters. Larger volumes are achieved by applying up to 100 pulses per second on the receptacle.
The maximum volume of the dispensed liquid per receptacle is the receptacle volume. The receptacle can have a volume between 80 microliters to 800 microliters. The initial volume of liquid arranged in the receptacle can be between 10 microliters to 500 microliters.
The liquid depends on the usage field of the dispensing device. The liquid can contain at least one biological particle. The biological particles may be microorganisms such as bacteria, archaean, yeast, fungi, and viruses or cells, DNA, RNA, or proteins. The liquid may have a single or multiple of the aforementioned biological particles. The liquid can promote the growth of the biological particles, in particular cells, arranged in the liquid. Alternatively, the liquid can comprise merely liquids, e.g. one or more chemical reagents.
A control variable can be a variable by means of which liquid dispensing is controlled and/or by means of which the volume of liquid to be dispensed can be set. In particular, the control variable can be a time duration over which a valve of the dispensing device is kept open so that pressure is applied on the liquid. The valve can be part of the dispensing device, in particular the dispensing head, and can be fluidically connected to a pressure source. Alternatively, the control variable of the dispensing process can be the pressure to be applied on the liquid. The pressure to be applied on the liquid and the time duration depend on each other. That means, by knowing one of the two values the other value can be determined for a specific dispensing device. The pressure can be time dependent. In particular, the pressure applied on the liquid can be a time dependent function. Thus, the control variable can be a pressure integral.
10.04.2022 005A0017LU 6
LU501825
The control unit is an electric or electronic unit. The control unit can comprise one or more processors for processing data. Alternatively, the control unit can be a processor for processing data. In particular, the control unit can comprise a printed circuit board. The control unit can be used for controlling the dispensing device, in particular the dispensing head and/or the dispensing step.
A dispensing process, which comprises one or more dispensing steps, is dependent on a control variable value. This means, the dispensing process is performed by using the control variable value.
For example, a pressure applied on the liquid arranged in the receptacle can be used in the dispensing process in order to dispense liquid from the receptacle. The dispensing process is performed by using the same control variable value. This means, all dispensing steps can be performed, in particular are performed, by using the same control variable value. Alternatively, it is possible that the dispensing process is performed by using different control variables. In other words, a part of the dispensing steps is performed by a control variable value and another part of the first dispensing steps is performed by another control variable value.
According to an embodiment the function for determining the volume of liquid to be dispensed can comprise at least one polynomial of n-th degree, wherein “n” is an integer number between 2 to 9, in particular 3. A polynomial of 3-th degree shows the highest accuracy. Using a polynomial has the advantage that a control variable, in particular the pressure applied on the liquid, can easily be determined so that the determined volume of liquid to be dispensed corresponds or basically corresponds with a predetermined volume of liquid. The determination of the control variable is particularly easy if the function is an inverse function. The provision of an inverse function, in particular polynomial, has the advantage that the control variable, in particular pressure to be applied on the liquid, can be calculated very accurate. This is possible as in the inverse function the function can be solved after the control variable, in particular pressure to be applied on the liquid.
Thus, in particular only, the control variable has to be set in order to receive a desired volume of liquid that is dispensed in the dispensing process.
The function can comprise a first function part that is dependent on the liquid to be dispensed.
Additionally, the function can comprise a second function part that is dependent on a further liquid.
A function result can be the volume of liquid to be dispensed. Said volume of liquid to be dispensed can be a sum of a first function result of the first function part and a second function result of the
10.04.2022 005A0017LU 7
LU501825 second function part. Splitting the function in two parts has the advantage that the training process can also be split into two processes.
In a first training processes the first function part can be identified by using the liquid of interest, namely the liquid to be dispensed. In a second phase the second function part can be identified by using the further liquid. At least one coefficient of the first function part can be dependent on the liquid to be dispensed and at least one coefficient of the second function part can be dependent on the further liquid. The at least one coefficient of the first function part can be identified in the first training phase and/or the at least one coefficient of the second function part can be identified in the second training phase. Both training processes are discussed below more in detail. The first function part can be a polynomial of n-th degree and/or the second function part can be a polynomial of n-th degree. Both polynomials can have the same degree.
The further liquid can be water. Water has the advantage that it does not cost much. A further advantage of using water is that the second function result corresponds or basically corresponds to a second function part result that is based on the liquid to be dispensed. In other words, the second function result is equal or similar to a function result that is based on the liquid to be dispensed.
The first function part can be independent of the volume of the liquid arranged in the receptacle.
Additionally or alternatively, the first function part can be dependent on the control variable of a dispensing step, in particular the pressure applied to the liquid arranged in the receptacle. A first function result of the first function part can be calculated by using a polynomial of n-th degree, in particular wherein n is an integer number between 2 to 9, in particular 3. The control variable, in particular pressure applied to the liquid, can be the variable of the polynomial. Thus, by choosing the applied pressure the first function result can be calculated. The first function part can have the following equation:
F1 = (ao + a1*U +... + An*U") wherein “F1” is the first functional result, “u” is the control variable, “ao … an” are the constants of the polynomial of the first function part and “n” is an integer number.
The dispensing device can comprise a pressure sensor for measuring pressure within the receptacle. In particular, the pressure sensor measures the pressure in a non-liquid area of the
10.04.2022 005A0017LU 8
LU501825 receptacle and/or above the liquid. The pressure sensor can be attached on a line of the dispensing head by means of which the receptacle is applied with pressure. In a dispensing process, the dispensing head is arranged on the receptacle and does not contact the liquid arranged in the receptacle.
The second function part can be dependent of the volume of the liquid arranged in the receptacle.
Additionally or alternatively, the second function part can be dependent of the control variable of a dispensing step, in particular pressure applied to the liquid arranged in the receptacle. A second function result of the second function part can be calculated by using at least one polynomial of m- th degree, in particular wherein m is an integer number between 2 to 9, in particular 3. The volume of the liquid can be multiplicated with the result of the polynomial wherein the control variable, in particular pressure applied to the liquid, can be the variable of the polynomial.
A second function result of the second function part can be calculated by using several polynomials of m-th degree, wherein m is an integer number. The number of polynomials of the second function part can corresponds with the value of the m-th degree. Each of the polynomials can be multiplicated with the volume of liquid arranged in the receptacle. However, the volumes of liquid arranged in the receptacle that are multiplicated with the polynomials differ from each other in their power. The second function part can have the following equation:
F2 = v1 # (Co + C1*U + Ca*U? +... + Cm*U”) + VI? # (Cet + Cme2®U + Cmas TU? +... + Coma *UT) +... + VIH (Cymer + Cent RU + Centmea *US +... + Came ¥UM) wherein “u” is the control variable, “Co … Cnm+1” are the constants of the polynomial, “vl” is the volume of the liquid arranged in the receptacle and “n” and “m” are integer values. In an embodiment the integer values “n” and “m” can have the same value.
Thus, the volume of liquid to be dispensed can be calculated as follows:
VD = F1+ F2 wherein "VD" is the volume of liquid to be dispensed, “F1” is the first function result and “F2” is the second function result.
10.04.2022 005A0017LU 9
LU501825
Using the second functional part being dependent of the volume of liquid arranged in the receptacle has the advantage that the volume of liquid to be dispensed can be set very accurate to the predetermined volume of liquid. This is possible as it is recognized that the volume of liquid arranged in the receptacle has a significant impact on the accuracy of the dispensing step and/or dispensing process.
In an operation mode of the dispensing device the volume of liquid arranged in the receptacle “vI” corresponds to the volume of liquid to be dispensed. In the training process discussed below more in detail, the volume of further liquid arranged in the receptacle was used to determine the coefficients of the second function part.
According to an embodiment the setting of the volume of liquid to be dispensed can be dependent of the control variable of a dispensing step and/or the volume of liquid arranged in the receptacle.
By considering at least one of said two variables, in particular both variables, the control unit accurately sets the volume of liquid to be dispensed in an operation mode of the dispensing device.
In the operation mode of the dispensing device the control unit can set the volume of liquid to be dispensed such that it corresponds or basically corresponds with a predetermined volume of liquid.
Thereto, the control variable, in particular pressure applied to the liquid, is set such that the volume of liquid dispensed in the dispensing step corresponds with or basically corresponds with the predetermined volume of liquid. The predetermined volume of liquid can be provided by the operator of the dispensing device.
The pressure applied to the liquid can be the control variable of the setting process. That means, the control unit determines the control variable, in particular pressure to be applied to the liquid, such that the volume of liquid to be dispensed or that is dispensed in a dispensing process corresponds with or basically corresponds with the predetermined volume of liquid. Thus, the control of the operation dispensing process is easy as the control unit has to identify a control variable, in particular a pressure value, that leads to that the volume of liquid to be dispensed corresponds with or basically corresponds with the predetermined volume of liquid. With “basically corresponds” it is meant that it is regarded as sufficient that the volume of liquid to be dispensed is within a predetermined range around the predetermined volume of liquid.
The control unit can determine the control variable, in particular pressure to be applied to the liquid,
10.04.2022 005A0017LU 10
LU501825 on the basis of a predetermined volume of the liquid to be dispensed. Using a polynomial has the advantage that the control variable value, in particular the pressure applied on the liquid, can easily be determined so that the determined volume of liquid to be dispensed corresponds or basically corresponds with a predetermined volume of liquid. The determination of the control variable is particularly easy if the function is an inverse function. The provision of an inverse function, in particular polynomial, has the advantage that the control variable value, in particular pressure to be applied on the liquid, can be calculated very accurate. This is possible as in the inverse function the function can be solved for the control variable value, in particular pressure to be applied on the liquid. Thus, in particular only, said parameter has to be set in order to receive a wished volume of liquid that is dispensed in the operation dispensing process.
The pressure applied to the liquid can be the control variable of the setting process. That means, the control unit determines the control variable, in particular pressure to be applied to the liquid, such that the volume of liquid to be dispensed or that is dispensed in a dispensing step corresponds with or basically corresponds with the predetermined volume of liquid. Thus, the control of the operation dispensing process is easy as the control unit has to identify a control variable, in particular a pressure value, that leads to that the volume of liquid to be dispensed corresponds with or basically corresponds with the predetermined volume of liquid. With “basically corresponds” it is meant that it is regarded as sufficient that the volume of liquid to be dispensed is within a predetermined range around the predetermined volume of liquid.
The volume of liquid arranged in the receptacle can be determined before the liquid is dispensed in the dispensing process. The volume of liquid arranged in the receptacle can be measured.
Additionally or alternatively the volume of liquid arranged in the receptacle can be determined on the basis of an initial filing volume of liquid arranged in the receptacle and the dispensed liquid volume. The initial filing volume can be the volume that e.g. a user inserts into the receptacle.
Furthermore, the volume of liquid arranged in the receptacle can be determined on the basis of a stored volume of liquid arranged in the receptacle and the dispensed liquid volume, wherein the stored volume of liquid arranged in the receptacle corresponds with the volume of liquid arranged in the receptacle before a previous dispensing step is performed. The determined volume of liquid arranged in the receptacle can be stored and thus can be used in a future dispensing step as “stored volume of liquid arranged in the receptacle”.
The dispensed liquid volume can correspond with the predetermined volume of liquid dispensed in
10.04.2022 005A0017LU 11
LU501825 a previous dispensing step. Alternatively, the dispensed liquid volume can correspond with the sum of predetermined volumes of liquids dispensed in several previous dispensing steps. It is also possible to measure the dispensed liquid volumes and to use said measured volume for determining the volume of liquid arranged in the receptacle. Additionally or alternatively, it is also possible to determine the dispensed liquid volume on the basis of the control variable, in particular pressure applied on the liquid.
The dispensing device can comprise a target carrier holder for a target carrier. The target carrier holder can comprise at least one target receptacle for receiving the dispensed liquid. The target carrier holder can be arranged below the receptacle or the carrier for carrying the at least one receptacle. The target carrier can be a multiwell plate.
According to an embodiment the value of the determined volume of liquid arranged in the receptacle can depend of a predetermined threshold. In particular, the control unit can set the value of the determined volume of liquid to be 0 when the volume of liquid corresponds with the predetermined threshold or is lower than the predetermined threshold. In this case the second function part result is 0. Such an embodiment has the advantage that the volume of liquid to be dispensed can be determined faster in comparison to an embodiment when the first and second function part results have to be calculated. This is possible as it has been recognized that the volume of liquid arranged in the receptacle has no or no significant influence on the accuracy of setting the volume of liquid to be dispensed to correspond or basically correspond with the predetermined volume of liquid. The predetermined threshold can be 20 microliter.
After the control variable is determined, the setting is finalized. The determined control variable can be applied in the dispensing device, in particular the pressure can be applied on the liquid, in order to perform the dispensing step. In the dispensing step a volume of liquid is dispensed.
According to an embodiment a first training process can be performed. In the first training process the control unit can determine the at least one coefficient of the first function part. Additionally or alternatively, a second training process can be performed. In the second training process the control unit and/or a data processing device can determine the at least one coefficient of the second function part. The advantage of performing two training processes is that the training processes can be performed at different times. Thus, it is possible to determine the coefficients of the first function part and afterwards the functions of the second function part or vice verse. Alternatively, it is
10.04.2022 005A0017LU 12
LU501825 possible that the training processes are performed at the same time. The two training process have to be performed with the same dispensing device. The dispensing device is the device for which the at least one function shall be defined. The data processing device is an electric or electronic unit. The data processing device comprises one or more processors for processing data. Alternatively, the data processing device can be a processor for processing data. In particular, the data processing device can comprise a printed circuit board.
The function used in the first training process corresponds to the first function part discussed above. That means, after performing the first training process the coefficients of the first function part are known.
The first training process is performed by using liquid. This means, liquid is dispensed by performing the at least one dispensing process that comprises at least one dispensing step. The first training process is performed without using the further liquid. In the first training process at least one coefficient of the first function part can be determined by using a predetermined training volume of liquid to be dispensed and a dispensed liquid volume. Additionally or alternatively at least one coefficient of the first function part can be determined by using a control variable of the dispensing step.
At least one coefficient, in particular all coefficients, of the first function part can determine such that the volume of dispensed liquid corresponds or basically corresponds with the predetermined volume of liquid to be dispensed. In particular, the at least one coefficient, in particular all coefficients, can be determined such that a difference between the volume of dispensed liquid and the predetermined volume of liquid to be dispensed is minimal. The at least one coefficient, in particular all coefficients, can be determined by using a regression analysis, in particular a least square algorithm. Both options provide an easy possibility to determine the function for determining the volume of liquid to be dispensed. With “basically corresponds” it is meant that it is regarded as sufficient that the volume of liquid to be dispensed is within a predetermined range around the predetermined volume of liquid.
In the first training process specific data has to be available in order to determine the at least one coefficient, in particular all coefficients, of the first function part. The data comprises information about the control variable value of the dispensing step and the volume of liquid that is dispensed.
By knowing said data, in particular for a plurality of dispensing steps of the first training process,
10.04.2022 005A0017LU 13
LU501825 and the predetermined volume of liquid to be dispensed the control unit can determine the at least one coefficient of the first function part. Additionally or alternatively, it is possible to determine the at least one coefficient, in particular all coefficients, by using the data tuple and a predetermined number of dispensing steps.
The second training process is performed by using the further liquid. This means, further liquid is dispensed by performing the at least one dispensing process that comprises at least one dispensing process. The second training process is performed without using the liquid. In the second training process at least one coefficient of the second function part can be determined by using a predetermined training volume of liquid to be dispensed and a dispensed liquid volume.
Additionally or alternatively, it is possible to determine the at least one coefficient, in particular all coefficients, by using the data triple and a predetermined number of dispensing steps. Additionally or alternatively at least one coefficient of the second function part can be determined by using a control variable of the dispensing step. Likewise to the first training process, a user of the dispensing device can enter the predetermined training volume into the dispensing device.
A training function can be determined in the second training process. The training function can comprise a first training function part and a second training function part. The training function, in particular the first training function part and the second training function part, can be a polynomial.
The training function can be of the same type as the function discussed above that comprises the first function part and the second function part. “Same type” means that the training function can be a polynomial of the same degree as the function and dependent on the same variable. However, “same type” does not mean that the coefficient values are identical.
The first training function part can be defined as follows:
T1 = (to + *U +... + th*UN) wherein “T1” is the first training function part result, “u” is a control variable, “to … tn” are the constants of the polynomial of the first training function part and “n” is an integer value.
The second training function part can be defined as follows:
T2 = VI * (Co + cı*U + c2*U? +. + Cm*U") + VI? * (Cet + Ca FU + Cmss FU? +... + Comm *UM)
10.04.2022 005A0017LU 14
LU501825 +... + VIN # (Cymer + Cen-timsa FU + Cin-1)m+ 3702 + Lt Cam *UM) wherein “T2” is the second training function part result, “u” is the control variable, “co … Cnm=1” are the constants of the polynomial, “VI” is the volume of the liquid arranged in the receptacle and “n” and “m” are integer values. In an embodiment the terms “n” and “m” can have the same value.
The at least one coefficient, in particular all coefficients, of the training function can be determined such that the volume of dispensed liquid corresponds or basically corresponds with the predetermined volume of liquid to be dispensed. In particular, the at least one coefficient, in particular all coefficients, can be determined such that a difference between the volume of dispensed liquid and the predetermined volume of liquid to be dispensed is minimal. The at least one coefficient, in particular all coefficients, can be determined by using a regression analysis, in particular a least square algorithm. Both options provide an easy possibility to determine the function for determining the volume of liquid to be dispensed. With “basically corresponds” it is meant that it is regarded as sufficient that the volume of liquid to be dispensed is within a predetermined range around the predetermined volume of liquid. A user of the dispensing device can enter the predetermined training volume into the dispensing device. The control unit and/or the data processing device can determine the aforementioned coefficients.
In the second training process the coefficients of the training function are determined. That means, the coefficients of the first training function and the second training function are determined.
Thereto, the control unit can set the at least one coefficient, in particular all coefficients, such that the volume of dispensed further liquid corresponds or basically corresponds with the predetermined volume of further liquid to be dispensed. In particular, the control unit can set the at least one coefficient, in particular all coefficients, such that a difference between the volume of dispensed liquid and the predetermined volume of liquid to be dispensed is minimal. The control unit can determine the at least one coefficient, in particular all coefficients, by using a regression analysis, in particular a least square algorithm. Both options provide an easy possibility to determine the function for determining the volume of liquid to be dispensed. With “basically corresponds” it is meant that it is regarded as sufficient that the volume of liquid to be dispensed is within a predetermined range around the predetermined volume of liquid.
In the second training process a data triple has to be available in order to determine the at least one coefficient, in particular all coefficients, of the training function. The data triple comprises
10.04.2022 005A0017LU 15
LU501825 information about the volume of liquid arranged in the receptacle, the control variable value of the dispensing step and the volume of liquid that is dispensed. By knowing said data, in particular for a plurality of dispensing steps of the second training process, and the predetermined volume of liquid to be dispensed, the control unit can determine the at least one coefficient of the first function part.
Additionally or alternatively, it is possible to determine the at least one coefficient, in particular all coefficients, by using the data triple and a predetermined number of dispensing steps.
The control unit can determine that the second training function part corresponds to the second function part. That means, that the second training function part is used in the setting of volume of liquid to be dispensed in the operation mode of the dispensing device. Thus, the first training function part is ignored in the operation mode of the dispensing device.
According to an aspect of the invention an aforementioned dispensing device is used in a method according to the invention. The aforementioned method can be performed for several receptacles.
Thus, it is possible that a function is selected for each of the receptacles, respectively. That means, if the receptacles are filled with different volumes of liquid, different functions can be used for setting the volumes of liquid to be dispensed from the respective receptacle.
According to a further aspect of the invention a computer program product is provided wherein the computer program product comprises instructions which, when the program is executed by the control unit executes the steps of the inventive method. The control unit can cause the dispensing device to carry out the steps of the inventive method. Additionally, a computer-readable data carrier is provided wherein the computer-readable data carrier has stored thereon the computer program product. Also a data carrier signal is provided wherein the data carrier signal carries the computer program product.
In the figures, the subject matter of the invention is shown schematically, with identical or similarly acting elements being mostly provided with the same reference signs. Therein shows:
Fig. 1 a cross section view of a part of a dispensing device according to a first embodiment,
Fig.2 across section view of a part of a dispensing device according to a second embodiment,
Fig.3 a flow chart of the method for setting the volume of liquid to be dispensed according to the
10.04.2022 005A0017LU 16
LU501825 invention wherein the method is performed in the dispensing device according to the first or second embodiment,
Fig.4 adiagram showing the first training process,
Fig.5 — a diagram showing the second training process and
Fig.6 a perspective view of a part of a dispensing device.
Fig. 1 shows a cross section of a part of a dispensing device 5 according to a first embodiment. In particular, fig. 1 shows a hollow dispensing line 15 of a dispensing head 8. The dispensing head 8 is arranged in its dispensing position in which a dispensing line 15 is arranged on a receptacle 2 comprising liquid 1. Thus, the dispensing head 8 is not in direct contact with the liquid 1. The dispensing head 8 comprises a seal 16 that is arranged between the dispensing line 15 and the receptacle. Additionally, the dispensing is electrically connected with a non-shown control unit. The control unit can control at least one valve arranged in the dispensing head 8 for applying the pressure to the liquid arranged in the receptacle 2.
The receptacle 2 is arranged on a carrier 7 and comprises an outlet opening 4 at its bottom.
Additionally, the receptacle 2 comprises an inlet opening 3 through which liquid 1 can be inserted into the receptacle 2. The inlet opening 3 and the outlet opening 4 are arranged at ends of the receptacle 2 that are opposite to each other.
By applying a pressure on the liquid 1 by means of the dispensing line 15 a droplet is dispensed from the receptacle 2. The pressure apply is indicated by the arrow in figure 1. The pressure enters the receptacle via the inlet opening 3. A pressure sensor 10 is attached on the dispensing line 15.
The pressure sensor 10 is configured to measure the pressure arranged in the area of the receptacle 2 that is arranged above the liquid 1. Additionally, it is possible to measure a time duration in which the pressure is applied to the liquid 1. In order to apply a pressure on the liquid 1 a non-shown valve is opened.
Fig. 2 shows a cross section of a part of a dispensing device 5 according to a second embodiment.
The second embodiment differs from the first embodiment in the structure of the carrier 7. The carrier 7 does not have a receptacle 2 that can be released from the carrier 7. The receptacle 2 and
10.04.2022 005A0017LU 17
LU501825 the carrier 7 are formed as one part. Each of the receptacles 2 has the outlet opening 4 at its bottom. Likewise, to the embodiment shown in fig. 1, the outlet opening 4 has such a size that capillary forces are so high that liquid 1 cannot flow out of the receptacle 2 if no pressure is applied on the liquid by means of the dispensing head 8. As is evident from fig. 2, the control unit 9 is connected to the dispensing head 8.
The dispensing device 5 comprises several liquid acquisition devices 17. Each of the liquid acquisition devices 17 comprises a source 18 for emitting a light beam and receiver 19 for receiving the emitted light beam. The liquid acquisition device 17 is arranged below the carrier 7 and a holder 6 for holding the carrier 7. In particular, the liquid acquisition device 17 is attached to the lower surface of the holder 6 that faces a target carrier 12 discussed below.
The liquid acquisition device 17 is arranged such that a dispensed liquid passes between the source 18 and the receiver 19 and, thus, interrupts the non-shown light beam. Thus, the liquid acquisition device 17 acquires that a liquid is dispensed from the first receptacle 2. Each of the first receptacles 2 of the carrier 7 is assigned to a liquid acquisition device 17. Thus, the number of liquid acquisition devices 17 corresponds with the number of first receptacles 2 from which liquid is dispensed. The liquid acquisition devices 17 are electrically connected to the control unit 9.
A target carrier 12 is arranged below the carrier 7. The target carrier 12 comprises a plurality of target receptacles 13 for receiving the liquid dispensed from first receptacles 2 of the carrier 7. A target carrier holder 11 is provided that holds the target carrier 12. The target carrier holder 11 moves the target carrier 12 relative to the carrier 7. The control unit 9 is electrically connected with the target carrier holder 11.
The dispensing head 8, the carrier 7 and the target carrier 12 can move relative to each other. The control unit 9 controls the movement of at least one of said components with respect to the remaining components.
As is described below more in detail, the control unit 9 is configured to set a volume of liquid to be dispensed from the receptacle 2by using a function for determining a volume of liquid to be dispensed, wherein the function is dependent on the liquid 1 to be dispensed and on a further liquid. The further liquid can be water. The liquid is the liquid of interest for the user of the dispensing device 5 and that is dispensed in a dispensing step from the dispensing device 5.
10.04.2022 005A0017LU 18
LU501825
Fig. 3 shows a flow chart of the method for setting the volume of liquid to be dispensed according to the invention wherein the method is performed in the dispensing device 5 according to the first or second embodiment. In the following, an operation mode of the dispensing device 5 is explained below.
In a first step S1 the user enters the predetermined volume of liquid 1 to be dispensed into the dispensing device 5 and the volume of liquid that is arranged in at least one first receptacle 2.
Thereto, the dispensing device 5 can have an input means like a keyboard and/or touch display. The user can enter one volume of liquid to be dispensed by each receptacle 2. Alternatively, it is possible to enter a volume of liquid to be dispensed separate for each receptacle 2. The control unit 9 receives the aforementioned data. In the following, it is explained how the control unit 9 sets the volume of liquid to be dispensed from one receptacle 2. The same process discussed below is applied to all receptacles 2 from which liquid shall be dispensed.
In a second step S2, the control unit 9 sets a volume of liquid 1 to be dispensed by considering the entered, predetermined volume of liquid to be dispensed. In particular, the control unit 9 sets the volume of liquid 1 to be dispensed such that it corresponds or basically corresponds with the predetermined volume of liquid 1 that was entered in the first step S1. Thereto, the control unit 9 controls the dispensing head 8 such that a control variable, in particular the applied pressure or the time duration over which the valve is kept open, is set such so that the determined volume of liquid that is dispensed corresponds or basically corresponds with the predetermined volume of liquid.
The pressure can be time dependent. In particular, the pressure applied on the liquid can be a time dependent function. Thus, the control variable can be a pressure integral.
In the following, it is explained more in detail how the volume of liquid to be dispensed is set by the control unit 9. A possibility is to use a function, in particular a polynomial, to calculate the volume of liquid to be dispensed. The function comprises a first function part and a second function part. The first function part of the function is defined as followed:
F1 = (ao + ar*u + az*u? + as*u3)
The second function part is defined as follows:
10.04.2022 005A0017LU 19
LU501825
F2 = vl * (co + C1*U + Ca*U? + c3*0U°) + VI? * (C4 + CS*U + CE*U? + C7*U*) + VIP * (cg +
Co*U + C1o*U? + C11*U*)
Thus, the function is defined as follows:
VD = F1 +F2 wherein "VD" is the volume of liquid to be dispensed, “F1” is the first function result and “F2” is the second function result, “u” is the control variable, “ao … a3” are the constants of the polynomial of the first function part, “Co … cam+1” are the constants of the polynomial of the second function part, “vil” is the volume of the liquid arranged in the receptacle and “n” and “m” of the equation shown above have the value “3”. In another non shown embodiment, the terms “n” and “m” can alternatively have another value than 3.
The volume of liquid to be dispensed VD corresponds with the sum of the first function result and the second function result.
The first function part is dependent on the liquid that is dispensed. That means, the coefficients are determined dependent on the liquid to be dispensed in a first training process. The second function part is dependent on the further liquid. That means, the coefficients of the second function part are determined dependent on the further liquid in a second training process. The further liquid can be water. The first and second training process are made in a step SO that is previous to the first step
S1 and is explained in figures 4 and 5 more in detail.
The function result VD is calculated by using a polynomial of 3° degree for both the first function part and the second function part wherein the pressure u applied on the liquid 1 is the variable of the two function parts, respectively. Alternatively, the first function part and the second function part can comprise one or more polynoms with other degrees.
The control unit sets the control variable u applied to liquid 2 such that the calculated volume of liquid to be dispensed corresponds or basically corresponds with the predetermined volume of liquid to be dispensed that was entered in the first step S1. As the function is an inverse function the control unit 9 can easily determine the control variable u.
10.04.2022 005A0017LU 20
LU501825
In a third step S3 the control unit 9 acts on the dispensing head 8 such that the determined pressure is applied on the liquid 2. This leads to that liquid is dispensed from the receptacle wherein the dispensed liquid has the volume of liquid to be dispensed that was determined in the second step s2.
Fig. 4 shows a diagram showing the first training process. In the first training process the user of the dispensing device enters a predetermined volume of liquid to be dispensed in a substep SO1.
Additionally, the user enters a volume of liquid arranged in the receptacle and/or a control variable.
In a second substep S02 one or several dispensing steps are performed wherein each of the dispensing processes comprises one or more dispensing step. Each of said dispensing processes or dispensing steps is performed by dispensing liquid. Said dispensed liquid is of interest for the user and is dispensed in the operation mode of the dispensing device as discussed in fig. 3.
After performing the dispensing process a data triple is known for each dispensing step. The data triple comprises information about volume of dispensed liquid, the control variable and the volume of liquid that is arranged in the receptacle. The dispensing processes and/or steps can differ from each other in the control variable value. Additionally, the predetermined volume of liquid to be dispensed is known from the first substep S01. The volume of dispensed liquid can be measured and/or determined.
In a third step, the control unit determines on the basis of said values the coefficients of the first function part. The first function part is defined as follows.
F1 = (ao + a1*U + ax*u? + a3*U°) wherein “F1” is the first function result, “u” is the control variable, “ao … a3” are the constants of the polynomial of the first function part.
The first function result corresponds with the volume of liquid to be dispensed. As the control variable is known the control unit 9 and/or a non-shown data processing device can determine the coefficients of the first function part so that the function result correspond or basically correspond to the predetermine volume of liquid to be dispensed. After performing the third substep S03, the coefficients of the first function part and thus the first function part is known so that the first training process is finalized.
10.04.2022 005A0017LU 21
LU501825
Fig. 5 shows a diagram showing the second training process. In the second training process the user of the dispensing device enters a predetermined volume of liquid to be dispensed in a first substep
S11. Additionally, the user enters a volume of liquid arranged in the receptacle and/or a control variable. In a second substep S12 one or several dispensing processes comprising at least one dispensing step are performed. Each of said dispensing processes or dispensing steps is performed by dispensing further liquid. Said further liquid is not of interest for the user and is not dispensed in the operation mode of the dispensing device as discussed in fig. 3.
After performing the dispensing process a data triple is known for each dispensing step. The data triple comprises information about the volume of dispensed further liquid, the control variable and the volume of further liquid that is arranged in the receptacle for each dispensing step. The dispensing processes and/or steps can differ from each other in the control variable value. The volume of dispensed further liquid can be measured and/or determined.
In a third substep S13 the control unit 9 and/or the data processing device determines the coefficients of the second function part in that it determines the coefficients of a training function.
The training function comprises a first training function part and a second training function part.
The first training function part is defined as follows:
T1 = (to +t1*uU + to*u? + ts*u3) wherein “T1” is the first training function part result, “u” is a control variable and “to ... tn” are the constants of the polynomial of the first training function part.
The second training function part is defined as follows:
T2 = vl * (Co + C1*u + Ca*U? + c3*u®) + VI2* (C4 + Cs*U + Cs*U2 + c7*u°) + VI? * (Cs +
CoŸU + C1o*U2 + C11*U°) wherein “T2” is the second training function part result, “u” is the control variable, “co ... ¢11" are the constants of the polynomial and “vI" is the volume of the liquid arranged in the receptacle.
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LU501825
The first and second training function are polyonomials of 3'*-degree. Alternatively, the first and second training function can be polynomials with a degree other than 3, i.e. the terms “n” and “m” have the value 3. The sum of both training function results corresponds to a training function result.
The control unit 9 sets the coefficients of the first training function part and of the second training function part so that the training function result corresponds to the predetermined volume of liquid that is entered by the user. This is possible as the control variable and the volume of liquid arranged in the receptacle 2 are known for each dispensing step.
After the coefficients of the first training function part and the second training function part are determined, the control unit 9 and/or the data processing device assigns in a fourth substep S14 that the second training function part corresponds to the second function part. That means, the coefficients of the second training function part corresponds to the coefficients of the second function part. Thus, after the fourth substep S14 all the coefficients of the function that is used in the operation mode are known.
Fig. 6 shows a perspective view of a part of a dispensing device 5 for dispensing liquid located in a receptacle 2, wherein the view shows more details of the dispensing device 5 than in the figures land 2.
The dispensing device 5 comprises a dispensing head 8. The dispensing head 8 is configured to dispense liquid located in the receptacle 2. Thereto, the dispensing head 8 has a pneumatic system including one or more valves (not shown in the figure) by means of which at least one receptacle 2 or several receptacles 2 can be provided with an impulse pressure that causes the liquid to drop from the outlet opening 4 of the respective receptacle 2.
Also, the device 5 comprises a holder 6, in which the carrier 7 is mounted in a detachable manner.
The dispensing head 8 is moveable relative to the holder 6 by means of a motor system (not shown in the figure). In particular, the dispensing head 8 can be moved relative to the carrier 7 so that the liquid of different receptacles 2 can be dispensed in sequence. Alternatively or additionally, it is possible that the carrier 7 and/or the holder 6 moves relative to the dispensing head 8.
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LU501825
Reference Signs: 1 liquid 2 receptacle 3 inlet opening 4 outlet opening 5 dispensing device 6 holder 7 carrier 8 dispensing head 9 control unit 10 pressure sensor 11 target carrier holder 12 target carrier 13 target receptacle 15 dispensing line 16 seal 17 liquid acquisition device 18 source 19 receiver
F1 first function part result
F2 second function part result an coefficient of first function a coefficient of second function tn coefficient of first training function u control variable vl volume of liquid arranged in the receptacle
VD function result
S0-S4 method steps
S01-S03 method steps of first training process
S11-S14 method steps of second training process

Claims (1)

10.04.2022 005A0017LU 24 LU501825 Patent Claims
1. Method for setting a volume of liquid to be dispensed from a receptacle (2) by using a function for determining a volume of liquid to be dispensed, wherein the receptacle (2) comprises an inlet opening (3) for inletting liquid (1) into the receptacle (2) and an outlet opening (4) for dispensing liquid (1) from the receptacle (2), when a pressure is applied on the liquid (1), wherein the function is dependent on the liquid (1) to be dispensed and on a further liquid.
2. Method according to claim 1, characterized in that a. the function is at least one polynomial of n-th degree and/or in that b. the volume of liquid to be dispensed is set by using at least one polynomial of n-th degree, wherein n is an integer number between 2 to 9, in particular 3.
3. Method according to claim 1 or 2, characterized in that the function comprises a first function part that is dependent on the liquid (1) to be dispensed and a second function part that is dependent on a further liquid.
4. Method according to claim 3, characterized in that a. the volume of liquid to be dispensed is a sum of a first function result of the first function part and a second function result of the second function part and/or in that b. at least one coefficient of the first function part is dependent on the liquid to be dispensed and at least one coefficient of the second function part is dependent on the further liquid and/or in that
C. the first function part is a polynomial of n-th degree and/or the second function part is a polynomial of m-th degree.
5. Method according to at least one of the claims 1 to 4, characterized in that the further liquid is water.
6. Method according to at least one of the claims 1 to 5, characterized in that a. the first function part is independent of the volume of the liquid (vl) arranged in the receptacle (2) and/or in that b. the first function part is dependent of a control variable of a dispensing step, in particular the pressure applied to the liquid (1) arranged in the receptacle (2).
10.04.2022 005A0017LU 25 LU501825
7. Method according to at least one of the claims 3 to 6, characterized in that a. a first function result (F1) is calculated by using a polynomial of n-th degree, in particular wherein n is an integer number between 2 to 9, in particular 3, and/or in that b. a first function result (F1) is calculated by using a polynomial of n-th degree, wherein the control variable, in particular the pressure applied to the liquid (1), is the variable of the polynomial and/or in that
C. a first function result (F1) is calculated by using the following equation F1 = (ao + a1*U +... + An*U") wherein “u” is a control variable, “ao … an” are the constants of the polynomial of the first function and “n” is an integer value.
8. Method according to at least one of the claims 1 to 7, characterized in that a. the second function part is dependent of the volume of the liquid (vl) arranged in the receptacle (2) and/or in that b. the second function part is dependent of the control variable, in particular pressure applied to the liquid (1) arranged in the receptacle (2).
9. Method according to at least one of the claims 1 to 8, characterized in that a. a second function result (F2) is calculated by using at least one polynomial of m-th degree, in particular wherein m is an integer number between 2 to 9, in particular 3, wherein the volume of liquid (vl) arranged in the receptacle (2) is multiplicated with the result of the polynomial and/or in that b. a second function result (F2) is calculated by using at least one polynomial of m-th degree, wherein the control variable, in particular pressure applied to the liquid (1), is the variable of the polynomial and the volume of liquid (vl) arranged in the receptacle (2) is multiplicated with the result of the polynomial.
10. Method according to at least one of the claims 1 to 9, characterized in that a. a second function result (F2) is calculated by using several polynomials of m-th degree, in particular wherein the number of polynomials corresponds with the value
10.04.2022 005A0017LU 26 LU501825 of the m-th degree and/or in that b. a second function result (F2) is calculated by using the following equation: F2 = vl * (co + c1*U + Ca*U? +. + CmFUT) + VIZ * (Cet + Ca FU + Css F2 +... + Comm FU)
+... + VIH (Cymer + Cent RU + Centmea *US +... + Came ¥UM) wherein “u” is the control variable, “Co … Cnm+1” are the constants of the polynomial, “vi” is the volume of the liquid arranged in the receptacle and “n” and “m” are integer values.
11. Method according to at least one of the claims 1 to 10, characterized in that the setting of the volume of liquid to be dispensed is dependent of a control variable of a dispensing step and/or the volume of liquid (vl) arranged in the receptacle.
12. Method according to one of the claims 1 to 11, characterized in that a. the volume of liquid to be dispensed is set such that it corresponds to or basically corresponds to a predetermined volume of liquid and/or in that b. the control variable is set such that the volume of liquid dispensed in the dispensing step corresponds or basically corresponds with a predetermined volume of liquid and/or in that
C. the pressure to be applied to the liquid (1) is determined on the basis of a predetermined volume of the liquid to be dispensed and/or the volume of the liquid (vl) arranged in the receptacle (2).
13. Method according to at least one of the claims 1 to 12, characterized in that the volume of liquid (vl) arranged in the receptacle (2) is determined before the liquid (1) is dispensed in the dispensing step.
14. Method according to at least one of the claims 1 to 13, characterized in that in a dispensing step the set volume of liquid is dispensed.
15. Method according to at least one of the claims 1 to 14, characterized in that a first training process is performed, wherein in the first training process at least one coefficient of the first function part is determined.
10.04.2022 005A0017LU 27 LU501825
16. Method according to claim 15, characterized in that a. the first training process is performed by using liquid (1) and/or in that b. the first training process is performed without using the further liquid.
17. Method according to claim 15 or 16, characterized in that a. at least one coefficient of the first function part is determined by using a predetermined training volume of liquid to be dispensed and a dispensed liquid volume and/or in that b. at least one coefficient of the first function part is determined by using a control variable of the dispensing step.
18. Method according to claim 17, characterized in that a. the at least one coefficient, in particular all coefficients, is set such that the volume of dispensed liquid corresponds or basically corresponds with the predetermined volume of liquid to be dispensed and/or in that b. the at least one coefficient, in particular all coefficients, is set such that a difference between the volume of dispensed liquid and the predetermined volume of liquid to be dispensed is minimal and/or in that
C. the at least one coefficient, in particular all coefficients, is determined by using a regression analysis, in particular a least square algorithm.
19. Method according to at least one of the claims 1 to 18, characterized in that a second training process is performed, wherein in the second training process at least one coefficient of the second function part is determined.
20. Method according to claim 19, characterized in that a. the second training process is performed by using further liquid and/or in that b. the second training process is performed without using the liquid (1).
21. Method according to claim 19 or 20, characterized in that a training function which comprises a first training function part and a second training function part is determined in the second training process.
22. Method according to claim 21, characterized in that the first training function part is defined
10.04.2022 005A0017LU 28 LU501825 as follows: T1 = (to + *U +... + th*U"N) wherein “T1” is the first training function part result, “u” is a control variable, “to … tn” are the constants of the polynomial of the first training function part and “n” is an integer value.
23. Method according to claim 21 or 22, characterized in that the second training function part is defined as follows: T2 = v1# (Co + CI*U + Ca*U? +... + Cm*U”) + VI? * (Cet + Cmsa FU + Css *UZ +... + Coma *UT)
+... + VI * (Cin-1)m+1 + Cin-nm+2*U + Cin-i)m+37 02 +... + Cnm+1 *UM) wherein “T2” is the second training function part result, “u” is the control variable, “co … Cam+1" are the constants of the polynomial, “vl” is the volume of the liquid arranged in the receptacle and “n” and “m” are integer values.
24. Method according to at least one of the claims 21 to 23, characterized in that a. at least one coefficient of the training function is determined by using a predetermined training volume of further liquid to be dispensed and a dispensed further liquid volume and/or in that b. at least one coefficient of the training function is determined by using a control variable of the dispensing step.
25. Method according to claim 24, characterized in that a. the at least one coefficient, in particular all coefficients, is determined such that the volume of dispensed further liquid corresponds or basically corresponds with the predetermined volume of further liquid to be dispensed and/or in that b. the at least one coefficient, in particular all coefficients, is determined such that a difference between the volume of dispensed further liquid and the predetermined volume of further liquid to be dispensed is minimal and/or in that
C. the at least one coefficient, in particular all coefficients, is determined by using a regression analysis, in particular a least square algorithm.
26. Method according to at least one of the claims 21 to 25, characterized in that the second
10.04.2022 005A0017LU 29 LU501825 training function part corresponds to the second function part.
27. Dispensing device (5) for dispensing liquid (1), in particular a dispensing device (5) for executing at least one of the claims 1 to 26, wherein the dispensing device (5) comprises a holder (6) for holding a carrier (7) comprising at least one receptacle (2), wherein the receptacle (2) has an inlet opening (3) for inletting liquid (1) into the receptacle (2) and an outlet opening (4) for dispensing liquid (1) from the receptacle (2), a dispensing head (8) for providing a pressure on the receptacle (2) and a control unit (9) that is configured to set a volume of liquid to be dispensed from the receptacle (2) by using a function for determining a volume of liquid to be dispensed, wherein the function is dependent on the liquid (1) to be dispensed and on a further liquid.
28. Dispensing device (5) according to claim 27, characterized in that the dispensing device (5) comprises a target carrier holder (11) for a target carrier (12) comprising at least one target receptacle (13) for receiving the dispensed liquid.
29. Using at least one dispensing device (5), in particular according to claim 27 or 28, in a method according to at least one of the claims 1 to 26.
30. Computer program product comprising instructions which cause that a control unit (9) executes the method steps according to at least one of the claims 1 to 26.
31. Computer-readable data carrier having stored thereon the computer program product of claim 30.
32. Data carrier signal carrying the computer program product of claim 30.
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WO1997015394A1 (en) * 1995-10-24 1997-05-01 Smithkline Beecham Corporation Microwell plates
WO2001071311A2 (en) * 2000-03-17 2001-09-27 Nanostream, Inc. Electrostatic systems and methods for dispensing droplets
US20030003027A1 (en) * 2000-02-25 2003-01-02 Jens Albert Microdosing device for the defined delivery of small self-contained liquid volumes
US7427379B1 (en) * 1999-03-19 2008-09-23 Biotage Ab Liquid dispensing apparatus
US20100112718A1 (en) * 2008-10-31 2010-05-06 Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. Device For Receiving A Liquid And Also Device For Applying Liquids On Sample Carriers And Method For This Purpose
FR3095763A1 (en) * 2018-05-09 2020-11-13 Family Self Care DEVICE AND METHOD FOR DISTRIBUTION OF LIQUID DROPS
US20210268491A1 (en) * 2018-02-01 2021-09-02 Labcyte Inc. Method for dispensing drops of different volumes

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997015394A1 (en) * 1995-10-24 1997-05-01 Smithkline Beecham Corporation Microwell plates
US7427379B1 (en) * 1999-03-19 2008-09-23 Biotage Ab Liquid dispensing apparatus
US20030003027A1 (en) * 2000-02-25 2003-01-02 Jens Albert Microdosing device for the defined delivery of small self-contained liquid volumes
WO2001071311A2 (en) * 2000-03-17 2001-09-27 Nanostream, Inc. Electrostatic systems and methods for dispensing droplets
US20100112718A1 (en) * 2008-10-31 2010-05-06 Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. Device For Receiving A Liquid And Also Device For Applying Liquids On Sample Carriers And Method For This Purpose
US20210268491A1 (en) * 2018-02-01 2021-09-02 Labcyte Inc. Method for dispensing drops of different volumes
FR3095763A1 (en) * 2018-05-09 2020-11-13 Family Self Care DEVICE AND METHOD FOR DISTRIBUTION OF LIQUID DROPS

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