LU501663B1 - Method for determining a function for determining a volume of liquid to be dispensed - Google Patents

Abstract

The invention relates to method for determining a function for determining a volume of liquid to be dispensed from a receptacle comprising an inlet opening for inletting a liquid into the receptacle and an outlet opening for dispensing liquid from the receptacle when a pressure is applied on the liquid, wherein the method comprises a first data acquisition process in which several first dispensing steps are performed that are dependent on a first control variable value and a first number of dispensing steps, which are performed until all liquid is dispensed from the receptacle, is automatically determined and wherein a second data acquisition process in which several second dispensing steps are performed that are dependent on a second control variable value and a second number of dispensing steps, which are performed until all liquid is dispensed from the receptacle, is automatically determined, wherein the function is determined on the basis of the determined first number of dispensing steps and the determined second number of dispensing steps.

Description

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LU501663

Method for determining a function for determining a volume of liquid to be dispensed

The invention relates to a method for determining a function for determining a volume of liquid to be dispensed and a control unit executing the method. 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,

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LU501663 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 device 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 there the available liquid volume is small.

In known devices a function is used to determine the volume of liquid to be dispensed. However, it is often necessary to determine a specific function for the liquid that shall be dispensed. As the dispensing device is used for dispensing a plurality of liquids a plurality of functions has to be determined. However, the determination of the function is a time-consuming task.

The object of the invention is to provide a method by means of which a function for determining a volume of liquid to be dispensed can be determined quickly.

The object is solved by a method for determining a function for determining a volume of liquid to be dispensed from a receptacle comprising an inlet opening for inletting a liquid into the receptacle and an outlet opening for dispensing liquid from the receptacle when a pressure is applied on the liquid, wherein the method comprises a first data acquisition process in which several first dispensing steps are performed that are dependent on a first control variable value and a first number of dispensing steps, which are performed until all liquid is dispensed from the receptacle, is automatically determined and wherein a second data acquisition process in which several second dispensing steps are performed that are dependent on a second control variable value and a second number of dispensing steps, which are performed until all liquid is dispensed from the receptacle, is automatically determined, wherein the function is determined on the basis of the determined first number of dispensing steps and the determined second number of dispensing steps.

Another object of the invention is to provide a dispensing device by means of which the function can be determined quickly.

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LU501663

The objective is solved by a dispensing device, 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 for dispensing liquid from the receptacle, an acquisition device for automatically determining whether a liquid is dispensed from the receptacle and a control unit that is configured to determine a number of dispensing steps, which are performed until all liquid is dispensed from a receptacle and that is configured to determine a function on the basis of the determined number of dispensing steps.

The invention has the advantage that the function can be determined quickly. Thus, the dispensing device can be used for a plurality of liquids without the disadvantage of a long-time taking process of adapting the function to the liquid to be dispensed. This is possible as the determination whether a liquid is dispensed is automatically determined by the acquisition device. Therefore, the first number of dispensing steps and the second number of dispensing steps can be automatically determined by the dispensing device. Thus, the manually tasks to be done by an operator of the dispensing device are reduced to a minimum in order to determine the function. In addition, no hardware or software changes have to be done for determining the function. Thus, it is possible to provide a liquid specific function in an easy and accurate manner.

With “automatically” it is meant that the acquisition device can determine itself whether a liquid is dispensed or not. That means, the decision can be taken without an involvement of the operator of the dispensing device. The acquisition device is an electric or electronic device.

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)

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LU501663 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 embodiment each receptacle bottom has at least one outlet opening. Said embodiment can be used ifthe carrier has 384 or more receptacles.

The receptacle into which the liquid is filled in the first data acquisition process and the receptacle into which the liquid is filled in the second data acquisition process can be the same. However, it is possible that the receptacles differ from each other. This has the advantage that the process for determining the function is faster as the data acquisition processes can be performed parallel to each other.

The carrier can have one or more receptacles. Carriers that have more one receptacle are also 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 can have a diameter between 60pm (micrometer) and 200um, in particular 100pm. The dispensed liquid can be a liquid droplet or a liquid jet and/or have a volume of at least 10 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

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LU501663 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. 5 The 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. By considering the control variable for determining the function, a function can be gathered by means of which the volume of liquid to be dispensed can be accurately determined.

The first control variable value and the second control variable value have different values. Each of the control variables can be a pressure integral between 20 mbar*ms (Millibar*Milliseconds) and 300 mbar*ms.

As is explained below more in detail data that are needed for determining the function are gathered in a training mode. In the training mode at least two data acquisition processes are performed. That means, the function determination can be based on more than two data acquisition processes. The more data acquisition processes are provided the more accurate the function can be determined.

The result of the data acquisition process is the number of dispensing steps.

The expression “dispensing step” means the process in which pressure is applied on the liquid so that it is dispensed from the receptacle. As is discussed above a liquid droplet or a liquid jet can be dispensed from the receptacle. Additionally, dispensing process means the process in which pressure is applied in the receptacle in which no liquid is arranged. In this case no liquid will be dispensed in the dispensing step.

The control unit is an electric or electronic unit. The control unit can comprise one or more

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LU501663 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 configured such that a part of the control unit, in particular a processor, is arranged in the acquisition device for determining the number of dispensing steps, i.e. the first number of dispensing steps and the second number of dispensing steps if two data acquisition processes are performed. Alternatively, the acquisition device can transmit the information whether a liquid is dispensed to the control unit that is arranged outside the acquisition device. “Number of dispensing steps” is an integer number indicating the number of dispensing steps in which liquid is dispensed from the receptacle. In other words, said number indicates the number of dispensing steps which are performed until all liquid arranged in the receptacle is dispensed.

According to an embodiment the determination of the first number of dispensing steps and/or the second number of dispensing steps can comprise a contactless acquiring whether a liquid is dispensed from the receptacle. The acquisition can comprise an optical acquiring whether a liquid is dispensed from the receptacle. In that case the acquisition device can comprise a source for emitting a wave, in particular a light beam, and a receiver for receiving the wave, in particular the light beam. The acquisition device can be arranged below the receptacle and/or can be arranged such that the dispensed liquid has to pass between a passage between the source and receiver. This means, the dispensed liquid interrupts the emitted wave, in particular the light beam. Thus, the acquisition device acquires that a liquid is dispensed when the dispensed liquid interrupts the emitted wave, in particular light beam. If the light beam is not interrupted, no liquid is dispensed from the receptacle. Alternatively, other acquisition processes exist by means of which it is possible to determine whether a liquid is dispensed in a dispensing step.

The acquisition device can be electrically connected with the control unit. In particular, the acquisition device can transmit an acquisition result, in particular whether a liquid is dispensed, to the control unit. The control unit can trigger the acquisition device to start with the acquisition. In particular, the control unit can trigger the acquisition device to start with acquisition when the control unit acts on the dispensing head of the dispensing device to perform dispensing processes.

The control unit can trigger the dispensing head such that the total number of dispensing steps performed by the dispensing head will be greater as the number needed for emptying the receptacle. Therefore, the dispensing head will perform dispensing steps even though no liquid is arranged in the receptacle. Thus, it is ensured that the acquisition device will detect at least one

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LU501663 dispensing step in which no liquid is dispensed. If more receptacles are provided, an acquisition device can be assigned to a receptacle, respectively. This means, the number of acquisition devices corresponds with the number of receptacles.

The first number of dispensing steps is increased when it is detected that liquid is dispensed in the first dispensing step and/or the second number of dispensing steps is increased when it is detected that liquid is dispensed in the second dispensing step. Additionally, the first number of dispensing steps and/or the second number of dispensing steps can be saved.

The first number of dispensing steps is not increased when it is detected that liquid is dispensed in the first dispensing step and/or the second number of dispensing steps is not increased when it is detected that liquid is dispensed in the second dispensing step. The acquisition device can transmit to the control unit that no liquid is dispensed in the first data acquisition process and/or in the second data acquisition process. Thus, the control unit considers the last saved determined first number of dispensing steps and/or the last saved second number of dispensing steps for the determination of the function. Alternatively or additionally, a predetermined number of dispensing steps are performed wherein the predetermined number of dispensing steps is greater than the number of dispensed steps that are needed to dispense all liquid from the receptacle. In that case, it is ensured that the acquisition device acquires at least one dispensing step in which no liquid is dispensed from the receptacle.

Before performing the dispensing steps, the receptacle is filed with a predetermined volume of liquid. In particular, in the first data acquisition process a receptacle is filed with a predetermined volume of liquid and/or in the second data acquisition process a receptacle is filed with a predetermined volume of liquid. The predetermined volume of liquid used in the first data acquisition process can be the same as the predetermined volume of liquid used in the second data acquisition process. That means, the receptacle or both receptacles are filed with the same liquid volume. The liquid filing can be performed automatically by a filling device. Alternatively or additionally, an operator can fill the receptacle with the liquid.

According to an embodiment the first data acquisition process can be performed a predetermined number of times with the same control variable value. For example, the first data acquisition process can be performed with the same pressure applied on the liquid. For each of the performed first data acquisition processes the first number of dispensing steps is determined. An average of

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LU501663 the determined number of dispensing steps that are determined in the plurality of first data acquisition processes can be calculated. Said average value can be used for the determination of the function. By performing several first data acquisition steps using the same control variable value for the dispensing steps an accurate first number of dispensing steps can be determined. With “performed” it is also meant that several first data acquisition processes can be performed at the same time. In that case several receptacles are used.

Additionally, the control unit can check whether the determined first number of dispensing steps fulfills a predetermined condition. If several first data acquisition processes are performed, the predetermined condition can be that a difference between a determined first number of dispensing steps and a further first number of dispensing steps is outside a predetermined range. Additionally or alternatively, the predetermined condition can be that the control unit checks whether a difference between the determined first number of dispensing steps and the average of the determined number of dispensing steps is outside a predetermined range and/or greater than a threshold. If at least one of said conditions is not fulfilled, the first data acquisition process can be repeated and the control unit checks whether the newly determined first number of dispensing steps fulfill the predetermined condition.

The second data acquisition process can be performed a predetermined number of times with the same control variable value. For example, the second data acquisition process can be performed with the same pressure applied on the liquid. For each of the performed second data acquisition processes the second number of dispensing steps is determined. An average of the determined number of dispensing steps that are determined in the plurality of second data acquisition processes can be calculated. Said average value can be used for the determination of the function.

By performing several second data acquisition steps using the same control variable value for the dispensing steps an accurate second number of dispensing steps can be determined.

Additionally, the control unit can check whether the determined second number of dispensing steps fulfills a predetermined condition. If several second data acquisition processes are performed, the predetermined condition can be that a difference between a determined second number of dispensing steps and a further second number of dispensing steps is outside a predetermined range. Additionally or alternatively, the predetermined condition can be that the control unit checks whether a difference between the determined second number of dispensing steps and the average of the determined number of dispensing steps is outside a predetermined range and/or greater

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LU501663 than a threshold. If at least one of said conditions is not fulfilled, the second data acquisition process can be repeated and the control unit checks whether the newly determined second number of dispensing steps fulfill the predetermined condition.

According to an embodiment the first data acquisition process and the second data acquisition process can be performed at the same time. In particular, the first data acquisition process can be performed by using a first dispensing line of the dispensing head of the dispensing device and the second data acquisition process can be performed by using a second dispensing line of the dispensing head of the dispensing device. In said case the dispensing head of the dispensing device has at least two dispensing lines. The dispensing head can have eight dispensing lines. Using a dispensing head with several dispensing lines ensures that the data acquisition process can be executed quickly. In particular, by using a multiwell plate with 96 or more wells and a dispensing head with two or more dispensing lines a plurality of data acquisition processes can be performed at the same time.

A calibration process can be performed before the first and second data acquisition process are performed. The calibration process is useful when the dispensing head comprises more than one dispensing line. In the calibration process the dispensing lines are adjusted to each other. This means, the dispensing lines are adjusted such to each other that they show the same or identical behavior when a pressure is applied to the liquid arranged in the receptacle. For example, the pressure inside the receptacle, in particular the pressure course via time, is measured when the liquid is applied with pressure by means of the dispensing line. Thereto, the dispensing device can comprise a pressure sensor. In the calibration process it shall be ensured that the measured pressure in the receptacle resulting from a pressure apply by means of a first dispensing line is identical to a measured pressure in a further receptacle resulting from a pressure apply by a second dispensing line, when the same control variable value is used for the dispensing steps in the receptacle and the further receptacle.

A volume of dispensed liquid can be determined on the basis of the determined first number of dispensing steps. Likewise, a second volume of dispensed liquid can be determined on the basis of the determined second number of dispensing steps. As the predetermined volume of liquid that is arranged in the receptacle is known, the first volume of dispensed liquid can be easily determined by dividing said predetermined volume of liquid by the number of dispensing steps. Likewise, the second volume of dispensed liquid can be determined.

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LU501663

After performing at least one, in particular two, data acquisition processes a data triple is present comprising information about the number of dispensing steps that are needed so that the receptacle is empty, the volume of dispensed liquid and the control variable value that is applied on the receptacle in order to dispense the liquid. Based on said data it is possible to determine the function for determining the volume of liquid to be dispensed from a receptacle.

The function can be a polynomial of n-th degree, wherein n is an integer number between 2 to 9, in particular 3. The function can be independent of the volume of the liquid arranged in the receptacle.

Additionally or alternatively, the function can be dependent on the control variable, in particular pressure applied to the liquid arranged in the receptacle.

A function result of the function can be calculated by using a polynomial of n-th degree, in particular wherein n is an integer number between 2 to 6, in particular 3. The control variable, in particular pressure applied to the liquid, can be the variable of the polynomial. Thus, by choosing a control variable value, in particular the applied pressure, the function result can be calculated. The function can have the following equation:

F = (ao + a1*U +... + an*U”) wherein “F” is a function result, “u” is a control variable, “ao … an” are the constants of the polynomial of the function and “n” is an integer value.

As discussed above, 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 receptacle and/or above the liquid. The pressure sensor can be attached on a dispensing line of the dispensing head by means of which the receptacle is applied with pressure.

At least one coefficient, in particular all coefficients, of the function can be determined on the basis of the determined first volume of dispensed liquid and/or the determined second volume of dispensed liquid. Thereto, the at least one coefficient, in particular all coefficients of the function, is set such that the function result that corresponds with the volume of liquid to be dispensed corresponds or basically corresponds with the first volume of dispensed liquid and/or the second volume of dispensed liquid. As mentioned above the first volume of dispensed liquid and/or the

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LU501663 second volume of dispensed liquid are determined on the basis of the first number of dispensing steps and the second number of dispensing steps.

The at least one coefficient, in particular all coefficients of the function, can be set such that a difference between the function result and the volume of dispensed liquid that was determined in a data acquisition process is minimal. In particular the at least one coefficient can be set such that the difference between the function result and the first volume of dispensed liquid and/or the second volume of dispensed liquid is minimal. Additionally or alternatively the at least one coefficient is 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. As discussed above if more than two data acquisition processes are performed all gathered data are used for the determination of the function coefficients.

According to an embodiment the control unit can check whether the determined first volume of dispensed liquid fulfills a predetermined condition with respect to a function result. Likewise, the control unit can check whether the determined second volume of dispensed liquid and/or other determined volumes of dispensed liquid fulfill a predetermined condition with respect to a function result, respectively. The predetermined condition can be whether a difference between the function result and the determined first volume of dispensed liquid and/or determined second volume of dispensed liquid is outside a predetermined range and/or greater than a threshold. If this is the case, the predetermined condition is not fulfilled. The function result is calculated by using the function with the same control variable value as it is used when the first volume of dispensed liquid and/or the second volume of dispensed liquid is determined.

If the predetermined condition is not fulfilled, the at least one coefficient, in particular all coefficients, can be determined again. However, the first volume of dispensed liquid for which the predetermined condition is not fulfilled is not taken into account for the determination of the at least one coefficient, in particular all coefficients. Likewise, the second volume of dispensed liquid for which the predetermined condition is not fulfilled is not taken into account for the determination of the at least one coefficient, in particular all coefficients. Thus, a determined volume of dispensed liquid that results on e.g. a measuring failure is not considered in the determination of the coefficient or coefficients. Thus, by excluding said data in determining the function, a function can

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LU501663 be provided which determines the volume of liquid to be dispensed in an accurate manner.

A function that is determined in the aforementioned manner can be used in an operation mode of the dispensing device. That means, the function can be used in a dispensing process for setting a volume of liquid to be dispensed by the dispensing device. The operation mode differs from the training mode discussed above in that in the operation mode the function determined in the training mode is used whereas in the training mode the function is determined.

In the operation mode of the dispensing device the volume of liquid to be dispensed can be set 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 control variable, in particular 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 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 variable, in particular pressure to be applied to the liquid, can be determined 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

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LU501663 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 dispensing process.

The dispensing device can comprise a pressure sensor for measuring pressure within the receptacle. Additionally, 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.

According to an aspect of the invention a computer program product is provide wherein the computer program product comprises instructions which, when the program is executed by the control unit 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 invention wherein the method is performed in the dispensing device according to the first or second embodiment,

Fig. 4 a flow chart showing the determination of the function,

Fig. 5 a diagram showing the function result and the determined number of dispensing steps 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

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LU501663 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 for applying the pressure to the liquid arranged in the receptacle.

The receptacle 2 is arranged on a carrier 7 and comprises an outlet opening 4 at its bottom.

Additionally, the receptacle 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 that is arranged above the liquid. 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 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 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 acquisition devices 17. Each of the acquisition devices 17 comprises a source 18 for emitting a light beam and receiver 19 for receiving the emitted light beam. The acquisition device 17 is arranged below the carrier 7. In particular, the acquisition device 17 is attached to the lower surface of the carrier 7 that faces a target carrier 12 discussed below.

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LU501663

The 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 acquisition device 17 acquires that a liquid is dispensed from the receptacle. Each of the receptacles 2 of the carrier 7 is assigned to an acquisition device 17. Thus, the number of acquisition devices 17 corresponds with the number of receptacles 2 from which liquid is dispensed. The 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 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.

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 particular, 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. 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.

Alternatively, it is possible to enter a volume of liquid to be dispensed separate for each receptacle 2.

In a second step S2, a 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

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LU501663 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. À possibility is to Use a function, in particular a polynomial, to calculate the volume of liquid to be dispensed. In particular, the following equation is used to calculate the volume of liquid to be dispensed:

F = (ao + a,*U + ay*u? + az*u?) wherein ”F” is the function result and corresponds with the volume of liquid to be dispensed, “u” is the control variable, “ao … az” are the constants of the polynomial.

The coefficients of the function are determined in a data acquisition process. The data acquisition process is made in a step SO that is previous to the first step S1 and is explained in figure 4 more in detail. The function result F is calculated by using a polynomial of 3" degree wherein the pressure u applied on the liquid 1 is the variable of the polynom. Alternatively, polynoms with other degree may be used.

The control unit sets the control variable u applied to liquid 2 such that the calculated volume of liquid F 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.

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 flow chart showing the determination of the function. In a first substep SO1 at least two data acquisition processes are performed. However, it is clear that more than two data acquisition processes can be performed for determining the function.

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In a first data acquisition process a receptacle 2 is filed with a predetermined volume of liquid 1. A dispensing line 15 of the dispensing head is arranged on the first receptacle and a pressure is applied on the liquid on the basis of a first control variable value. The first control variable value can be a pressure value by means of which the liquid has to be applied. The control unit 9 controls the dispensing head that the pressure is applied on the liquid 2. A plurality of dispensing steps is performed until the first receptacle 2 is empty. The acquisition device 17 acquires whether a liquid is dispensed or not. If a liquid is dispensed a number of dispensing steps that can be stored in a memory of the acquisition device 17 or the control unit 19 is increased. When the acquisition device 17 does not acquire that liquid is dispensed the first data acquisition process is finished.

Alternatively, the first data acquisition process is finished if a predetermined number of dispensing steps is performed. The first number of dispensing steps is determined on the basis of the acquired information of the acquisition device 17.

The first data acquisition process is performed for a predetermined number of times, in particular three times. In particular, the control variable value used in the first dispensing steps is the same in each of the first data acquisition processes. The plurality of first data acquisition processes can be performed at the same time. In said cases the liquid of several receptacles is dispensed.

In a second data acquisition process a further receptacle 2 is filed with a predetermined volume of liquid. A further dispensing line 15 of the dispensing head is arranged on the second receptacle and a pressure is applied on the liquid on the basis of a second control variable value. The second control variable value can be a pressure value by means of which the liquid has to be applied and is different from the first control variable value. The control unit 9 controls the dispensing head that the pressure is applied on the liquid 2. A plurality of dispensing steps is performed until the second receptacle 2 is empty. The acquisition device 17 acquires whether a liquid is dispensed or not. If a liquid is dispensed a number of dispensing steps that can be stored in a memory of the acquisition device 17 or the control unit 19 is increased. When the acquisition device 17 does not acquire that liquid is dispensed the first data acquisition process is finished. Alternatively, the second data acquisition process is finished if a predetermined number of dispensing steps is performed. The second number of dispensing steps is determined on the basis of the acquired information of the acquisition device 17.

The second data acquisition process is performed for a predetermined number of times, in particular three times. In particular, the control variable value used in the second dispensing steps is

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LU501663 the same in each of the second data acquisition processes. The plurality of second data acquisition processes can be performed at the same time. In said cases the liquid of several receptacles is dispensed.

In a second substep S02 the results of the first and second data acquisition process are used to determine a dispensed volume of liquid, respectively. In particular, the first volume of dispensed liquid is determined that is dispensed in a first dispensing step in the first data acquisition process.

Thereto, the predetermined volume of liquid that was filed into the receptacle is divided by the first number of dispensing steps. Likewise, the predetermined volume of liquid that was filed into the further receptacle is divided by the second number of dispensing steps. Thus, the second volume of dispensed liquid is also determined in the second substep S02. If more than two data acquisition processes are performed, the volume of dispensed liquid of each dispensing process of said data acquisition processes is determined.

In a third substep S03 the control unit 9 checks whether the determined volume of dispensed liquids can be used in the determination of the function. Thereto, the determined first volume of dispensed liquid values of the first data acquisition processes and the determined second volume of dispensed liquid values of the second data acquisition processes are considered. In the following, the procedure is described for the first volume of dispensed liquid values. The same procedure is performed with the values of the second and other data acquisition processes.

In the third substep S03 the control unit 9 checks whether the first number of dispensing steps determined in the first data acquisition steps fulfill a predetermined condition. Thereto, an average value of the determined first number of dispensing steps is calculated. The predetermined condition is that a deviation of a determined first number of dispensing steps from the average value is greater than a threshold. If the condition is not fulfilled, the first data acquisition process is repeated for the first number of dispensing steps that does not fulfill the condition. The newly determined first number of dispensing steps is used for further determination of the function if it fulfills the predetermined condition. Thereto, a new average value has to be calculated the control unit checks again whether the determined first number of dispensing steps fulfill the predetermined condition.

In an embodiment non-shown in the figures, the third substep S03 can be performed before the second substep S02.

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If all determined first and second number of dispensing steps fulfill the predetermined condition, the method is continued in a fourth substep S04. In the fourth substep S04 the function is determined. In particular, in substep S04 the coefficients “ao ... an” of the polynomial function discussed above are determined. Thereto, the control unit 9 sets the coefficients such that a difference between the function result and the determined first volume of dispensed liquid and/or the second volume of dispensed liquid is minimal. If more than two volume of dispensed liquids are determined, said volumes of dispensed liquids are also considered for identifying the coefficients of the function. Alternatively or additionally, a regression analysis can be performed in order to identify the functions coefficients. After performing the fourth substep S04 the coefficients of the function are determined.

The function results of a function for which the coefficients are identified are shown in Fig. 5. In particular, fig. 5 shows a diagram showing the function result of the function dependent on the determined number of dispensing steps. In particular, the result of several data acquisition processes is shown in figure 5. The results are indicated by black dots. The function shown in fig. 5 is a straight-line L meaning that in this embodiment the number “n” of the polynomial function is 1.

However, in a non-shown embodiment the number “n” of the polynomial function can be greater than 1, in particular as discussed above.

In a fifth substep S05 the control unit 9 checks whether a predetermined condition between the function result and the determined volume of dispensed liquid is fulfilled. The condition can be whether a difference between the function result and the determined volume of dispensed liquid is within a range.

Fig. 5 shows a faulty number of dispensing steps N1 for which the determined volume of dispensed liquid significantly differs from the function result F, namely the calculated volume of dispensed liquid. In particular, the difference between the two volumes of dispensed liquid is greater than a predetermined threshold. Thus, the control unit 9 identifies that a failure happened by performing the data acquisition process resulting in the faulty number of dispensing steps N1.

Additionally, the control unit 9 repeats the determination of the function performed in the fourth substep S04. This means, the coefficients of the function are determined again. However, in this case the result of the data acquisition process that was identified as faulty is not considered for the determination of the coefficients in the fourth substep S04.

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If the control units 9 determined that the volumes of dispensed liquid of all data acquisition processes fulfill the predetermined condition, the function determination is finished in the sixth substep S06. In said case the function is identified. Thus, the training mode is finished and the function can be used in the operation mode.

Fig. 6 shows a perspective view of a part of a dispensing device 5 for dispensing liquid located in a receptacle 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. The dispensing device 5 can be formed as shown in fig. 1 and 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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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 acquisition device 18 source 19 receiver

L straight line

F function result an coefficient of function u control variable

N1 faulty number of dispensing steps

V1 volume of dispensed liquid calculated on the basis of the faulty number of dispensing steps

S1-S3 method steps

S01-S06 method substeps

Claims (1)

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1. Method for determining a function for determining a volume of liquid to be dispensed from a receptacle (2) comprising an inlet opening (3) for inletting a 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 method comprises a first data acquisition process in which several first dispensing steps are performed that are dependent on a first control variable value and a first number of dispensing steps, which are performed until all liquid (1) is dispensed from the receptacle (2), is automatically determined and wherein a second data acquisition process in which several second dispensing steps are performed that are dependent on a second control variable value and a second number of dispensing steps, which are performed until all liquid (1) is dispensed from the receptacle (2), is automatically determined, wherein the function is determined on the basis of the determined first number of dispensing steps and the determined second number of dispensing steps.

2. Method according to claim 1, characterized in that a. the determination of the first number of dispensing steps and/or the second number of dispensing steps comprises a contactless acquiring whether a liquid (1) is dispensed from the receptacle (2) in that b. the first number of dispensing steps is increased when it is detected that liquid (1) is dispensed in the first dispensing step and/or the second number of dispensing steps is increased when it is detected that liquid (1) is dispensed in the second dispensing step and/or in that

C. the first number of dispensing steps is not increased when it is detected that liquid (1) is dispensed in the first dispensing step and/or the second number of dispensing steps is not increased when it is detected that liquid (1) is dispensed in the second dispensing step.

3. Method according to claim 1 or 2, characterized in that a. in the first data acquisition process a receptacle (2) is filed with a predetermined volume of liquid and/or in the second data acquisition process a receptacle (2) is filed with a predetermined volume of liquid and/or in that

15.03.2022 005A0011LU 23 LU501663 b. a predetermined volume of liquid used in the first data acquisition process is the same as a predetermined volume of liquid used in the second data acquisition process.

4. Method according to at least one of the claims 1 to 3, characterized in that the first data acquisition process is performed a predetermined number of times with the same first control variable value.

5. Method according to claim 4, characterized in that a. an average value of the determined first number of dispensing steps is determined and/or in that b. a first data acquisition process is performed if a determined first number of dispensing steps does not fulfill a predetermined condition.

6. Method according to at least one of the claims 1 to 5, characterized in that the second data acquisition process is performed a predetermined number of times with the same second control variable value.

7. Method according to claim 6, characterized in that a. an average value of the second number of dispensing steps is determined and/or in that b. a second data acquisition process is performed if a determined second number of dispensing steps does not fulfill a predetermined condition.

8. Method according to at least one of the claims 1 to 7, characterized in that a. the first data acquisition process and the second data acquisition process are performed at the same time and/or in that b. the first data acquisition process is performed by using a first dispensing line of a dispensing head of a dispensing device and the second data acquisition process is performed by using a second dispensing line of the dispensing head of the dispensing device.

9. Method according to at least one of the claims 1 to 8, characterized in that a calibration process is performed before the first and second data acquisition process are performed.

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10. Method according to at least one of the claims 1 to 9, characterized in that a. a first volume of dispensed liquid is determined on the basis of the determined first number of dispensing steps and/or in that b. a second volume of dispensed liquid is determined on the basis of the determined second number of dispensing steps.

11. Method according to at least one of the claims 1 to 10, characterized in that the function is at least one polynomial of n-th degree, wherein n is an integer number between 2 to 9, in particular 3.

12. Method according to at least one of the claims 1 to 11, characterized in that a. the function is independent of the volume of the liquid arranged in the receptacle (2) and/or in that b. the function is dependent of the control variable.

13. Method according to at least one of the claims 1 to 12, characterized in that the function has the following equation F = (ao + a1*U +... + an*U”) wherein “F” is a function result, “u” is a control variable, “ao … an” are the constants of the polynomial of the function and “n” is an integer value.

14. Method according to at least one of the claims 1 to 13, characterized in that at least one coefficient, in particular all coefficients, of the function is determined on the basis of the determined first volume of dispensed liquid and/or the determined second volume of dispensed liquid.

15. Method according to at least one of the claims 1 to 14, characterized in that a. the at least one coefficient is set such that a difference between a function result and the first volume of dispensed liquid and/or the second volume of dispensed liquid is minimal and/or in that b. the at least one coefficient is determined by using a regression analysis, in particular a least square algorithm.

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16. Method according to at least one of the claims 1 to 15, characterized in that a. it is checked whether the determined first volume of dispensed liquid fulfills a predetermined condition with respect to a function result and/or in that b. it is checked whether the determined second volume of dispensed liquid fulfills a predetermined condition with respect to a function result.

17. Method according to claim 16, characterized in that the at least one coefficient is determined again without using the first volume of dispensed liquid for which the predetermined condition is not fulfilled and/or the second volume of dispensed liquid for which the predetermined condition is not fulfilled.

18. Method according to at least one of the claims 1 to 17, characterized in that in an operation mode of the dispensing device the determined function is used in a dispensing process for setting the volume of liquid to be dispensed.

19. Method according to claim 18, 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 with a predetermined volume of liquid.

20. Dispensing device (5), in particular for executing a method according to at least one of the claims 1 to 19, 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) for dispensing liquid (1) from the receptacle (2), an acquisition device (17) for automatically determining whether a liquid is dispensed from the receptacle and a control unit (9) that is configured to determine a number of dispensing steps, which are performed until all liquid (1) is dispensed from a receptacle (2) and that is configured to determine a function on the basis of the determined number of dispensing steps.

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21. Dispensing device (5) according to claim 20, characterized in that the dispensing device (5) comprises a pressure sensor (10) for measuring pressure within the receptacle (2).

22. Dispensing device (5) according to claim 20 or 21, 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.

23. Computer program product comprising instructions which cause that the dispensing device of at least one of the claims 20 to 22 executes the method steps according to at least one of the claims 1 to 19.

24. Computer-readable data carrier having stored thereon the computer program product of claim 23.

25. Data carrier signal carrying the computer program product of claim 23.