WO2019008044A1

WO2019008044A1 - Method for dispensing a liquid

Info

Publication number: WO2019008044A1
Application number: PCT/EP2018/068105
Authority: WO
Inventors: Jonas SCHÖNDUBE; Andre Gross; Michael MELL; Julian RIBA
Original assignee: Cytena Gmbh
Priority date: 2017-07-04
Filing date: 2018-07-04
Publication date: 2019-01-10
Also published as: LU100331B1

Abstract

The invention relates to a method for dispensing a liquid. Said method is characterized in that the liquid is dispensed from a dispensing device and in that an actual position of the liquid is determined following the dispensing of the liquid from the dispensing device.

Description

Method for dispensing a liquid

The invention relates to a method for dispensing a liquid. Moreover, the invention relates to a device for dispensing a liquid.

Applications in the field of single-cell genomics are known from the state of the art, in which a drop of liquid with a cell contained therein is introduced into a container in which a liquid reagent is contained. The liquid reagent is part of the chemical reaction that makes the DNA accessible to the cell. In order not to damage the cell and / or to access the DNA of the cell, the amount of reagent contained in the well is strictly regulated. So it often happens that only a part of a container bottom is wetted with the liquid reagent.

When dispensing the liquid drop from an output device located above the container, there is the problem that often the dispensed liquid drop lands next to the reagent contained in the container and thus does not come to the above-mentioned chemical reaction. This problem arises because due to the component tolerances of the dispensing device, such as manufacturing tolerances, it is not guaranteed that the liquid drop moves only in the vertical direction.

This increases the risk that the liquid drop lands next to the reagent in the container, the greater the distance between the container and the dispenser. Often, the distance between the dispenser and the container is about 15-25 mm (millimeters), which is already sufficient for the liquid drop to be due to the component tolerances present in the dispenser can land next to the reagent. Since the component tolerances of the output devices are not known, it is first determined in the laboratory operation whether the liquid drop is deposited in the reagent. US 2014/1 1 1 635 AI discloses a device used in semiconductor manufacturing. The device has an image sensor that detects an image of a target.

US 2007/086 021 A1 discloses a system for measuring a drop position. The device has two detectors, which are arranged rotated by 90 ° to each other.

EP 1 934 050 A2 discloses a device for the controlled deposition of drops on a substrate. The device has a plurality of cameras, which are arranged rotated to each other.

WO 201 7/184 776 A1 discloses a dispensing device for dispensing drops. The dispensing device has a detection station which contains two image sensors. By means of the image sensors, the actual position of the drop can be determined in two spatial directions. The image sensors are designed so that they can be moved along the path of movement of the droplet.

The object of the invention is therefore to provide a method by means of which it can be determined whether the liquid dispensed can be stored at a predetermined location.

The object is achieved by a method of the aforementioned type, characterized in that the liquid is dispensed from an output device and an actual position of the liquid is determined after dispensing the liquid from the dispensing device. Another object of the invention is to provide a device by means of which it can be determined whether the liquid dispensed can be deposited at a predetermined location. The object is achieved by a device which is characterized by an output device for dispensing the liquid and an evaluation device which determines an actual position of the liquid after dispensing the liquid from the dispensing device. According to the invention, it has been recognized that by determining the actual position of the liquid, a conclusion can be drawn as to whether the liquid and / or liquids subsequently dispensed from the dispensing device can be deposited at the desired location.

The amount of liquid dispensed can be specified by the user. In particular, the dispensing of the liquid can take place such that the dispensed liquid is a liquid drop or a liquid jet. The delivery of liquid can be discrete, the time intervals between the individual liquid discharges are predetermined and / or adjustable. In addition, the dispensed liquid, in particular a single, preferably biological, contain cell. In particular, each of the dispensed liquids, in particular a single, preferably biological, cell.

The drop of liquid may have a diameter of about 65 μιτι (microns) and / or a volume of about 150 pl (picolitre).

The liquid can be introduced into a sample carrier. In addition, the fluid can be stored on a sample carrier. The sample carrier can carry a reagent. By means of the reagent, the above-mentioned chemical reaction can be carried out. The Reagent may be, for example, a lysis buffer. Alternatively, a sample carrier is possible that carries no reagent.

The sample carrier can be designed as a container in which the reagent is arranged. The container may have an opening having a diameter of, for example, 4 mm (millimeters). In addition, the container may have oblique walls, so that the cross section of the container changes. The sample carrier can be designed as a microtiter plate having a plurality of containers. Alternatively, the sample carrier can be made planar. The reagent can be arranged on the sample carrier.

In a particular embodiment, the evaluation device can determine a trajectory of the liquid. In addition, the evaluation device can check whether the trajectory is running through a desired position.

By determining the trajectory of the liquid can be determined in a simple manner, whether the output liquid is stored to a predetermined location. The trajectory of the liquid depends on the component tolerances of the dispenser. This means that the determined trajectory takes into account the component tolerances. According to the invention, it has now been recognized that depositing the dispensed liquid into, for example, a reagent located in the sample carrier can be ensured if, as explained in more detail below, the determined trajectory is used.

Trajectory is understood to be the path of movement along which the liquid moves after being dispensed from the dispensing device until impinging on the sample carrier and / or the reagent. In addition, the determined trajectory corresponds to the trajectory of subsequent output by the output device Liquids. Thus, on the basis of the determination of the trajectory of an output liquid, the trajectory of fluids subsequently discharged from the output device is known. The sample carrier may have the desired position. This may be the case in cases where the sample carrier carries no reagent. Alternatively or additionally, the reagent may have the desired position. The desired position may have a desired point. In this case, it is checked whether the trajectory is running through the set point. Alternatively, the desired position may have a desired surface. In this case, it is checked whether the trajectory intersects the target surface and thus passes through the target position.

In a particular embodiment, the device may comprise a receiving device. For determining the actual position of the liquid, in particular of two spatial directions of the actual position, the receiving device can produce at least one image of the liquid dispensed from the dispensing device. In particular, a plurality of images of the liquid dispensed from the dispensing device can be produced by means of the receiving device. The images can be generated at different times depending on the time of liquid delivery. In particular, an image can be generated before the liquid hits the sample carrier and / or the reagent. As a result, different actual positions of the dispensed liquid can be determined at different times. The generation of the multiple images occurs at the same focus settings of the recording device. This means that in the production of the multiple images, the position of the focus, in particular a focal plane, of the recording device does not change. A focal plane is understood to mean a plane which has a focus of the recording device and has at least one region which is perpendicular to one optical axis of the recording device is. The focal plane can have a slightly curved course, which can also be compensated. In addition, the receiving device can in each case generate at least one image, in particular a plurality of images per dispensed liquid, of a plurality of successively dispensed liquids, in particular a plurality of successive liquid drops. In this case, the time of the generation of the image by the recording device may depend on the time of the liquid delivery. This procedure is useful when the dispensed liquid moves so fast that it can not produce more than one image per dispensed liquid.

Thus, with a first amount of liquid dispensed, the image may be generated at a time after the dispensing of liquid. For a subsequent second amount of liquid dispensed, the image may be generated at a different time after the liquid dispensing. The images are created for each liquid dispensed with the same focus settings. As a result, for a large number of dispensed liquids, the respective actual position can be determined at different times. The dispensed liquids can be part of the same sample and therefore of the same type. In addition, the amount of liquid dispensed may be the same for successive liquid discharges.

In order to determine the actual position of the liquid, in particular in a third spatial direction, at least one first other image of the liquid dispensed from the dispensing device and at least one second other image of the liquid dispensed from the dispensing device can be produced. It can at least a first other image by the receiving device and the at least one second other image are generated by a further receiving device of the device. Alternatively or additionally, the receiving device for determining the actual position of the liquid, in particular in a third spatial direction, at least produce a first different image of the liquid output from the dispensing device and at least one second other image of the liquid dispensed from the dispensing device.

When the first other image is generated, a focal plane is offset and / or rotated relative to the focal plane when the second image is generated. In particular, a focal plane of the receiving device is offset and / or arranged so as to be twisted relative to the focal plane of the further receiving device. The staggered arrangement of the two focal planes is realized by moving a focal plane to the other focal plane. The displacement can take place along a path, in particular along an optical axis of the receiving device and / or further receiving device.

By moving the focal plane can be determined in a particularly simple manner, the actual position of the liquid in the third spatial direction. In particular, it is advantageous that the receiving device and the further receiving device can be arranged to each other such that their optical axes are parallel or coaxial with each other. This means that the two recording devices need not be arranged twisted to each other, which is often not possible due to the lack of space. Alternatively or additionally, a focus of the recording device when generating the first other image, in particular along the optical axis of the recording device, offset from the focus of Receiving device when creating the second other image arranged. In particular, the focal plane of the recording device when generating the first other image, in particular along the optical axis of the recording device, offset and / or rotated to the focal plane of the recording device when generating the second other image arranged. In this case, only the receiving device is needed to determine the actual position of the liquid in the third spatial direction. The receiving device and / or the further receiving device can also generate other other images to determine the actual position of the liquid. In this case, the other images are generated by the fact that the focus, in particular the focal plane, respectively displaced along the optical axis and / or rotated.

In this case, the first other figure may be the aforementioned figure. This offers the advantage that by generating exactly two images, namely the image and the second image, the actual position of the liquid in three spatial directions can be determined.

In addition, at least one first other image and at least one second other image of a plurality of successive dispensed liquids can be produced by means of the receiving device and / or the further receiving device.

In addition, it is possible for a plurality of first other images and / or a second plurality of other images to be generated at different times. The times of generation of each of the first other images and / or the second individual other images may depend on the time of liquid delivery. As a result, the actual position of the liquid at different times, in particular from the discharge of liquid, be determined.

The device may have a displacement device for displacing the focus, in particular the focal plane, the receiving device and / or the further receiving device. In this case, the receiving device as a whole and / or the further receiving device as a whole and / or the sample carrier can be moved by means of the displacement device. Alternatively, it is possible for the displacement device to displace an objective of the recording device and / or the further recording device and / or to change the shape of a lens. The recording device can be a camera and / or have a stroboscope.

The further recording device can produce at least one further image. The focal plane of the further recording device can be arranged twisted to the focal plane of the recording device. In particular, the further receiving device may be arranged such that the optical axis of the receiving device and the further optical axis of the further receiving device are perpendicular to each other. By providing a further receiving device arranged in this way, the trajectory of the dispensed liquid can be determined even more accurately and / or without displacement of the focal plane than with only a single receiving device.

The evaluation device can determine an actual position of the liquid in a first spatial direction and a second spatial direction in the image. The first spatial direction may be perpendicular to the second spatial direction. In embodiments in which a plurality of images are generated, the evaluation device in each of the figures can determine an actual position of the liquid in the first and second spatial directions. When generating a plurality of images, an average of the actual position of the liquid and / or an average of a plurality of successive liquids in the first and second spatial directions can be determined. As a result, a scattering of the actual position in the first and second spatial directions can be compensated. This procedure is useful when the time periods between the generation of the images are very short.

In order to determine the actual position of the liquid in a third spatial direction, the evaluation device can determine an image property, in particular the same image property, the first other image and the second other image. The image characteristic may be the sharpness and / or the contrast and / or contour contrast and / or the frequency distribution in the image. Furthermore, a phase comparison or an interference measurement can be performed. Thus, the shorter the distance of the sample to the focus, in particular to the focal plane, the sharper the image. Thus, in a simple manner by determining an image characteristic, a conclusion can be drawn about the actual position of the liquid and / or the actual positions of the several successive liquids in the third spatial direction. In particular, based on the determined image properties in an extrapolation process, the actual position of the liquid in the third spatial direction can be accurately determined.

In embodiments in which more than two other images are generated, the accuracy of the actual position determination increases in the third spatial direction. The third spatial direction is perpendicular to the first spatial direction and to the second spatial direction. Moreover, the third spatial direction points in the same direction as the optical axis of the recording device.

The images generated by the further imaging device, in particular further illustrations and / or first further Illustrations and / or second additional illustrations can also be used to determine the actual position of the liquid. The evaluation device can evaluate these analogously to the images generated by the recording device and / or first other images and / or second other illustrations. By taking into account the images generated by the receiving device and the other recording devices, the actual position of the liquid can be determined precisely. The evaluation device can also determine an actual position of the output device. The determination of the actual position in all three spatial directions of the output device can be carried out analogously to the determination of the actual position of the liquid quantity. In particular, the determination of the actual position of the output device can be determined by means of the generated at least one image and / or at least one other image. Alternatively, the actual position of the dispenser may be determined in another way and / or entered by the user. The output device can be designed, for example, as a piezo dispenser.

In a particular embodiment, the evaluation device can determine the trajectory on the basis of the determined actual position of the liquid and / or the actual positions of the liquids and the determined actual position of the output device.

Alternatively or additionally, the evaluation device can determine the trajectory on the basis of the determined actual position of the dispensed liquid and / or the actual positions of the dispensed liquids at a first time and the determined actual position of the dispensed liquid and / or the actual positions of the dispensed liquids at a second time. This is possible in particular in the embodiments in which several images and / or several first other illustrations and several other second images by means of the receiving device and / or the other recording device are generated. As a result, the evaluation device can determine the trajectory of the liquid in all three spatial directions on the basis of the determined actual positions of the liquid. The determination can be made on the basis of an interpolation and / or extrapolation of the determined of the actual positions of the liquid quantity. In this case, a linear interpolation and / or extrapolation in which the trajectory has a linear course is possible. Alternatively, a parabolic interpolation and / or extrapolation leading to a parabolic course of the trajectory can be performed. Furthermore, other forms of trajectory can be considered.

Since the component tolerances of the dispenser do not change significantly over time, the paths of movement of the liquids following the liquid to be dispensed are also known. This means that, based on the determined trajectory, it is possible to predict the trajectories of the fluids to be dispensed in the future.

The check as to whether the trajectory is running through the desired position can be carried out manually by the user of the device, for example with the aid of a display device which displays the trajectory. Alternatively, the test can be carried out automatically by means of the, in particular electrical or electronic, evaluation device.

In addition, it can be checked by means of the evaluation device whether only a single liquid is dispensed by means of the dispensing device. If in the figure and / or in the first other figure and / or the second other figure more than one liquid is shown, the determination of the trajectory of the liquid is terminated and the dispensing parameters adjusted so that only a single drop of liquid per liquid ejection or liquid jet per liquid ejection is generated.

The device may have an offset device, which moves the output device and / or the sample carrier into a different position if, in particular by the evaluation device, it is determined that the trajectory is not passing through the desired position. In particular, the displacement device can move the dispensing device to the other position in which the trajectory passes through the desired position. Alternatively, the device may include a displacement device that moves the dispenser and a further displacement device that moves the sample carrier. In this case, the output device and the sample carrier are moved until it is determined that the trajectory no longer runs through the desired position. It is thereby achieved that the liquid dispensed, for example in laboratory operation, by means of the dispensing device is deposited in the reagent carried by the sample carrier at the desired location.

In a particular embodiment, it is possible to check at least once, in particular by means of the evaluation device, whether the actual position of the dispensed liquid coincides with another desired position. The test can be repeated at predetermined intervals and / or before the liquid hits the sample carrier and / or the reagent. The other desired position can be stored in a, in particular electrical or electronic, memory of the device. The other desired position may contain data regarding the spatial position of the liquids, in particular depending on the time from the liquid dispensing. If the actual position of the issued Liquid does not match the stored spatial position, recognizes the evaluation that the output from the output device liquid can not be stored in the desired location. Accordingly, the output device is shifted so far that the actual position, in particular the liquid dispensed in a subsequent step, coincides with the desired position.

In the event that the actual position of the dispensed liquid coincides with the other desired position, the dispenser is not moved.

The method according to the invention can also be carried out several times in succession. For this purpose, the liquids are dispensed successively by means of the dispensing device. In this case, the time interval between the dispensing of two liquids is selected such that in each case only a single liquid drop is shown in the illustration and / or in the first other image and / or in the second other image. In this case, the method described above is carried out for each liquid output in order to determine the respective trajectory. The individual trajectories can be averaged to obtain a single trajectory. Moreover, it is conceivable that after a predetermined operating time and / or a predetermined number of dispensed liquids of the device, the trajectory is determined again. This can avoid that, for example, due to a component wear during laboratory operation, the liquid dispensed is not stored at the selected position. According to one, in particular independent, inventive idea is provided according to a first aspect of a method for dispensing a liquid, which is characterized in that the liquid from a Issued output device and an actual position of the liquid after dispensing of the liquid from the output device is determined.

In a second aspect according to the first aspect, a trajectory of the liquid is determined.

In a third aspect according to the second aspect, it is checked whether the trajectory is running through a desired position. In a fourth aspect according to one of aspects 1 to 3, at least one image of the liquid dispensed from the dispensing device is generated to determine the actual position of the liquid.

In a fifth aspect according to one of aspects 1 to 4, to determine the actual position of the liquid, a first different image of the liquid dispensed from the dispensing device and at least one second other image of the liquid dispensed from the dispensing device is produced, wherein a focal plane of a receiving device during production of the the first other image offset and / or rotated to the focal plane of the recording device when generating the second other image is arranged.

In a sixth aspect of the fifth aspect, the first other image is the image.

In a seventh aspect according to any of aspects 4 to 6, an actual position of the liquid in a first spatial direction and in a second spatial direction in the image is determined. In an eighth aspect according to one of the aspects 5 to 7, to determine the actual position of the liquid in a third spatial direction, a Identifies image characteristic of the first other picture and at least one second other picture.

In a ninth aspect according to any one of aspects 1 to 8, an actual position of the output device is determined.

In a tenth aspect of any one of aspects 2 to 9 becomes

a. the trajectory is determined and / or determined on the basis of the determined actual position of the liquid and the determined actual position of the output device

b. the trajectory determined on the basis of the determined actual position of the liquid at a first time and the determined actual position of the liquid at a second time. In an eleventh aspect according to any one of aspects 2 to 10

a. moves the dispenser and / or a sample carrier in a different position when the trajectory is not running through the target position and / or will

b. moved the dispenser and / or a sample carrier in a different position in which the trajectory through the

Target position is running.

In a twelfth aspect according to one of aspects 1 to 1 1, it is checked whether the actual position coincides with another desired position.

In a thirteenth aspect, an apparatus for carrying out a method according to any one of aspects 1 to 12 is provided.

In a fourteenth aspect, there is provided an apparatus for dispensing a liquid characterized by a dispenser for dispensing the liquid and a dispenser Evaluation device that determines an actual position of the liquid after dispensing the liquid from the dispenser.

In a fifteenth aspect according to the thirteenth or fourteenth aspect, the evaluation device determines a trajectory of the liquid.

In a sixteenth aspect according to the fifteenth aspect, the evaluation device determines whether the trajectory is running through a target position. In a seventeenth aspect according to any one of aspects 1 3 to 1 6, a receiving device is provided, which is for generating

a. an illustration of the liquid dispensed from the dispenser and / or used to generate b. a first other image of the liquid dispensed from the dispenser and at least one second other image of the liquid dispensed from the dispenser.

In an eighteenth aspect according to any one of aspects 13 to 17, there is provided a shifting device for shifting a focus of the pickup device.

In a nineteenth aspect according to one of the aspects 1 3 to 1 8, a further receiving device is provided, which generates at least one further image, wherein a focal plane of the further receiving device is arranged rotated to the focal plane of the receiving device.

In a twentieth aspect according to one of aspects 1 3 to 19, the evaluation device determines in at least one image an actual position of the liquid in a first spatial direction and in a second spatial direction. In a twenty-first aspect according to any of aspects 13 to 20, the evaluation device for determining the actual position of the liquid in a third spatial direction determines an image characteristic of the first other image and the second other image.

In a twenty-second aspect according to any one of aspects 13 to 21, the evaluation device determines an actual position of the output device.

In a twenty-third aspect according to any one of aspects 13 to 22, the evaluation device determines

a. the trajectory based on the determined actual position of the liquid and the determined actual position of the output device and / or determines the evaluation device

b. the trajectory based on the determined actual position of the

Liquid at a first time and the determined actual position of the liquid at a second time.

In a twenty-fourth aspect according to any one of aspects 13 to 23,

a. the sample carrier on the target position and / or points

b. a reagent on the target position.

In a twenty-fifth aspect according to any one of aspects 13 to 24, an offset device and / or a further displacement device are provided which

a. moves the output device and / or the sample carrier in a different position when the evaluation determines that the trajectory does not run through the target position and / or the b. the dispenser and / or the sample carrier moved to another position, in which the trajectory passes through the desired range. In a twenty-sixth aspect according to any one of aspects 13 to 25, the evaluation device checks whether the actual position coincides with another desired position.

In the figures, the subject invention is shown schematically, wherein the same or equivalent elements are usually provided with the same reference numerals. Showing:

Fig. 1 is a front view of the device according to the invention according to a first embodiment and a sample carrier, Fig. 2 is a side view of the device according to the invention shown in Figure 1 according to the second embodiment and

3 is a front view of the device according to the invention according to the first embodiment, in which the output device is moved,

Fig. 4 is a front view of the device according to the invention according to a second embodiment and the sample carrier. The device shown in Figure 1 for introducing a liquid in the form of a liquid drop 1 in a sample carrier 2, which is designed as a container, has an output device 3 for dispensing the liquid drop 1 and an evaluation device 6 shown in FIG. In the sample carrier 2, a, in particular liquid, reagent 8 is arranged, which wets only a part of a sample carrier tray 9. The evaluation device 6 determines an actual position I after the liquid drop 1 has exited the dispensing device 6. In addition, the evaluation device 6 determines a dashed line shown in Figure 1 trajectory 4 of the liquid drop 1 based on the determined actual position I of the liquid drop. 1 The evaluation device 6 checks whether the trajectory 4 passes through a predetermined desired position S. The sample support bottom 9 has the desired position S. In particular, the desired position S corresponds to a desired point in the center of the sample carrier tray 9. However, the desired position S is not limited to the desired point.

As can be seen from FIG. 1, the trajectory 4 intersects the sample carrier base 9 at an intersection point E, which lies at a distance from the desired position S. This means that the liquid drop 1 dispensed from the dispensing device 3 is not deposited in the desired position on the sample carrier 2 and will land next to the reagent 8.

For determining the trajectory 4, by means of a receiving device 5 shown in FIG. 2, an image of the device, of the liquid drop 1 leaked out of the dispensing device 3, which is shown by a solid line, and of the sample carrier 2 is generated at a first time. Subsequently, by means of the receiving device 6, at a second point in time, an image of the device, of the liquid drop 1 which has emerged from the dispensing device 3 and which is represented by a dashed line, and of the sample carrier 2 is produced. The figure includes a plane extending in a first spatial direction x and a second spatial direction y.

Alternatively or additionally, by means of the receiving device 6 at a second other time an image of the device, another leaked from the dispenser 3 liquid drop 1 and the sample carrier 2 is generated. This is useful when the liquid drop 1 moves so fast that no two images can be generated. The actual position I of the liquid drop 1 at the first time differs from the actual position I of the liquid drop 1 at the second time. An optical axis 7 (shown in FIG. 2) runs perpendicular to the illustration or the illustrations.

In the first illustration, the evaluation device 6 determines the actual position I of the liquid drop 1 in the first spatial direction x and the second spatial direction y. In addition, the evaluation device 6 determines the actual position I of the liquid droplet I shown in dashed lines in the first spatial direction x and the second spatial direction y in the second illustration.

FIG. 2 shows a side view of the device shown in FIG. FIG. 2 shows the receiving device 1 and the evaluation device 6. In this case, the evaluation device 6 communicates by means of at least one electrical line data technology with the receiving device. 1 In particular, the images generated with the recording device 1 are transmitted to the evaluation device 6 for evaluation.

To determine the actual position I of the liquid drop 1 in a third spatial direction z, a first other image and a second other image are generated by means of the receiving device 5. Analogously to the illustration, the first other image and the second other image have a plane which extends in the first spatial direction x and the second spatial direction y. The first other image and the second other image differ from each other in the arrangement of the focus, in particular the focal planes F.

In Figure 2, a first layer 1 0 of the receiving device 5 is dashed and a second layer 1 1 of the receiving device 5 with a shown by solid line. The receiving device 5 arranged in the first position 10 is displaced along an optical axis 7 in the direction of the arrow P by means of a displacement device 16 in order to reach the second position 11. In this case, the first other image is generated when the receiving device 5 is arranged in the first layer 10. The second other image is generated when the receiving device 5 is arranged in the second position 11. In the arrangement of the receiving device 5 in the first layer 10, the liquid drop 1 is arranged in the focal plane F.

As a result of the displacement of the receiving device 5, the focal plane F of the receiving device 5 also shifts. As a result, the first other image has a different image characteristic, such as a different sharpness of the liquid drop 1, than the second other image. Since in the first layer 10 of the receiving device 5 the liquid drop 1 is arranged in the focal plane F and in the second layer 11 of the receiving device 5 the liquid drop 1 is not arranged in the focal plane F, the liquid drop 1 is shown sharper in the first other image than in the second other picture.

The evaluation device 6 can determine the actual position I of the liquid drop 1 in the third spatial direction z based on the image characteristic of the first other image and the image property of the second other image. Although not shown in Figure 2, there is a possibility that the pickup 5 will be further displaced along the optical axis 7 and more than two other images will be generated. The evaluation device 6 can now determine the trajectory 4 of the liquid drop 1 based on the actual positions of the liquid drop 1 in the three spatial directions at different times. alternative or additionally, the evaluation device 6 can use an actual position of the output device 3 to determine the trajectory 4. The actual position I of the dispensing device 3 can be determined in an analogous manner as the actual position I of the liquid drop 1 or otherwise determined.

The trajectory 4 is extrapolated on the basis of the determined actual positions I of the liquid drop 1. Thus, with knowledge of the two actual positions of the liquid drop 1 at different times, the trajectory 4 can correspond to a straight line which has the two actual positions. The trajectory 4 may alternatively be determined by other extrapolation methods.

Figure 3 shows a front view of the device according to the invention, in which the dispensing device 3 is displaced. In this case, a position 12 of the output device 3 is shown in dashed lines in Figure 3, which corresponds to the position of the output device 3 shown in Figure 1, in which the trajectory 4 does not run through the desired position S. In addition, in Figure 3, another position 13 of the dispenser 3 is shown in solid lines. In the other position 13, the dispensing device 3 is arranged such that the trajectory 4 of the liquid drop 1 passes through the desired position S. As already described above, the evaluation device 6 determines the trajectory 4 of the liquid drop 1. Thereafter, the evaluation device 6 or the user of the device checks whether the trajectory 4 of the liquid drop 1 passes through the desired position S. If this is not the case, the dispenser 3 is moved in the direction of the arrow P in one to three spatial directions until the trajectory 4 of the liquid drop 1 passes through the desired position S. The displacement of the output device 4 by means of a displacement device 17. In this case, the displacement device 17 is connected to the data processing device 4. In this case, the displacement device 17 will shift the output device 4 until it is determined that the trajectory 4 passes through the desired position S.

Although this is not apparent from FIG. 3, the dispensing device 3 is also displaced along the third spatial direction z to ensure that the trajectory 4 of the liquid drop 1 passes through the reagent 8.

Figure 4 shows a front view of the device according to a second embodiment. The device differs from the device shown in Figure 1 in that a further receiving device 14 is present. The further receiving device 14 is arranged such that an optical axis 15 of the further receiving device 14 extends perpendicular to the optical axis 7 of the receiving device 5. By means of the further recording device 14, an image can be generated by means of which inference can be drawn to the actual position of the liquid drop (1) in the second spatial direction y and the third spatial direction z. In addition, the further receiving device 14 can be moved analogously to the receiving device 5 along its optical axis 15, so that the actual position of the liquid drop 1 in the first spatial direction x can be determined. The displacement of the further receiving device 14 can be realized by means of a further displacement device 19. In addition, the device according to the second embodiment, the receiving device 5, according to which the above figures can be determined. Another difference to the device shown in Figure 1 is that the device has a further displacement device 18 for moving the sample carrier 2. The further displacement device 18 is connected to the data processing device 4. After determination of the trajectory 4, the displacement device 17 will be the output device 3 and the further displacement device 18 will move the sample carrier 2 until it is determined that the trajectory 4 is passing through the desired position S.

In the figures, the discharged liquid assumes the form of a liquid drop 1. The device can also be operated if the dispensed liquid has a different shape and, for example, is a liquid jet.

LIST OF REFERENCES:

1 drop of liquid

2 sample carriers

3 output device

4 trajectory

5 recording device

6 evaluation device

7 optical axis of the recording device

8 reagent

9 sample tray bottom

10 first position of the recording device

1 1 second position of the recording device

12 position of the dispenser

13 different position of the dispenser

14 more recording device

15 optical axis of the other recording device

1 6 Displacement device

1 7 displacement device

18 more displacement device

19 more displacement device

E intersection

F focal plane

I actual position

P arrow

S target position x first spatial direction

y second spatial direction

z third spatial direction

Claims

claims

1 . A method for dispensing a liquid, characterized in that the liquid is dispensed from an output device (3) and an actual position (I) of the liquid after dispensing of the liquid from the dispenser (3) is determined, wherein for determining the actual position (I) of the liquid generates at least one image of the output from the output device (3) liquid and an actual position (I) of the liquid in a first spatial direction (x) and in a second spatial direction (y) is determined in the figure, characterized in that for determining the actual position (I) the liquid in a third spatial direction (z) a first other image of the output from the output device (3) output liquid and at least a second other image of the output from the output device (3) liquid generated, wherein a focal plane (F) during Generating the first other image offset to the focal plane (F) in generating the second n other figure is arranged.

2. The method according to claim 1, characterized in that a trajectory (4) of the liquid is determined.

3. The method according to claim 2, characterized in that it is checked whether the trajectory (4) by a desired position (S) runs.

4. The method according to claim one of claims 1 to 3, characterized in that

a. the first other picture is the picture and / or that b. the focal plane (F) of a receiving device (5) is offset when generating the first other image and / or is arranged rotated relative to the focal plane (F) of the receiving device (5) when the second other image is generated.

5. The method according to any one of claims 1 to 4, characterized in that for determining the actual position (I) of the liquid in a third spatial direction (z) an image characteristic of the first other image and the at least one second other image is determined.

6. The method according to any one of claims 1 to 5, characterized in that an actual position (I) of the output device (3) is determined.

7. The method according to any one of claims 2 to 6, characterized in that

a. the trajectory (4) is determined on the basis of the determined actual position (I) of the liquid and the determined actual position (I) of the output device (3) and / or that b. the trajectory (4) is determined on the basis of the determined actual position (I) of the liquid at a first time and the determined actual position (I) of the liquid at a second time.

8. The method according to any one of claims 2 to 7, characterized in that

a. the output device (3) and / or a sample carrier (2) is moved to another position (13) when the trajectory

(4) does not pass through the desired position (S) and / or that b. the dispensing device and / or a sample carrier (2) is moved to another position in which the trajectory (4) passes through the desired position (S).

9. The method according to any one of claims 1 to 8, characterized in that it is checked whether the actual position (I) coincides with another target position.

10. Apparatus for carrying out a method according to one of claims 1 to 9.

1 1. A device for dispensing a liquid, comprising an output device (3) for dispensing the liquid, an evaluation device (6) which determines an actual position (I) of the liquid after dispensing the liquid from the dispensing device (3) and a receiving device (5) for generating an illustration of the output from the output device (3) liquid, wherein the evaluation device (6) in at least one image, an actual position (I) of the liquid in a first spatial direction (x) and in a second spatial direction (y) determined, characterized in that in order to determine the actual position (I) of the liquid in a third spatial direction (z), a first other image of the liquid dispensed from the dispensing device (3) and at least one second other image of the liquid dispensed from the dispensing device (3) can be produced, a focal plane (F) when generating the first other image offset from the focal plane (F) in the ore ugen the second other figure is arranged.

12. The apparatus of claim 10 or 1 1, characterized in that the evaluation device (6) determines a trajectory (4) of the liquid.

13. The device according to claim 12, characterized in that the evaluation device (6) determines whether the trajectory (4) by a desired position (S) runs.

14. Device according to one of claims 10 to 13, characterized by the receiving device (5) for generating the first other image of the liquid output from the dispensing device (3) and at least the second other image of the liquid dispensed from the dispensing device (3).

15. Device according to one of claims 10 to 14, characterized by a displacement device (16) for displacing a focus of the receiving device (5).

1 6. Device according to one of claims 10 to 15, characterized by a further receiving device (14) which generates at least one further image, wherein a focal plane of the further receiving device twisted to the focal plane (F) of the receiving device (5) is arranged.

1 7. Device according to one of claims 10 to 16, characterized in that the evaluation device (6) for determining the actual position (I) of the liquid in a third spatial direction (z) determines an image characteristic of the first other image and the second other image.

18. Device according to one of claims 10 to 17, characterized in that the evaluation device (6) determines an actual position (I) of the output device (3).

19. Device according to one of claims 10 to 18, characterized in that the evaluation device (6)

a. the trajectory (4) on the basis of the determined actual position (I) of the liquid and the determined actual position (I) of

Output device (3) determined and / or that b. the trajectory (4) is determined on the basis of the determined actual position (I) of the liquid at a first time and the determined actual position (I) of the liquid at a second time.

20. Device according to one of claims 10 to 19, characterized in that

a. the sample carrier (2) has the desired position (S) and / or that b. a reagent (8) has the desired position (S).

21. Device according to one of claims 10 to 20, characterized by a displacement device (17) and / or a further displacement device (18), the

a. the output device (3) and / or the sample carrier (2) moves into another position (13) when the evaluation device (6) determines that the trajectory (4) is not passing through the desired position (S) and / or

b. the output device (3) and / or the sample carrier (2) moves into another position (13), in which the trajectory (4) passes through the desired region (S).

22. Device according to one of claims 10 to 21, characterized in that the evaluation device (6) checks whether the actual position (I) coincides with another desired position.