METHOD FOR DETECTING A PARTICLE IN A CONTAINER FILLED WITH LIQUID

Abstract

The invention relates to a method for detecting a particle in a container filled with liquid, the method having the following steps: dispensing a liquid sample into the container, scanning a partial volume area of the container in order to detect a particle located in the liquid sample, characterized in that an upper limit and a lower limit of the partial volume area is determined in a calibration operation upstream of the dispensing process.

Claims

1-32. (canceled)

33. A method for detecting a particle (8) in a container (3) containing liquid (2), the method comprising the following steps: dispensing a liquid sample (5) into the container (3) in a dispensing operation; scanning a partial volume region (7) of the container (3) to detect a particle (8) located in the liquid sample (5); and determining an upper limit (9) and a lower limit (10) of the partial volume region (7), wherein the upper limit (9) and the lower limit (10) are determined in a calibration operation performed prior to the dispensing operation.

34. The method according to claim 33, wherein at least one of a liquid surface (16), a cross-sectional area of the container (3), and a container bottom (12) is determined in the calibration operation.

35. The method according to claim 33, wherein a container volume (13) of the container (3) is scanned in the calibration operation and a plurality of background images of the container volume (13) are recorded.

36. The method according to claim 35, wherein the calibration operation is carried out when a sample carrier (15) having multiple containers including the container (3) is inserted into a dispensing device (1), and in the calibration operation, a liquid sample (5) having a particle (8) is dispensed into the container (3) of the sample carrier (15).

37. The method according to claim 36, wherein the container volume (13) is scanned after the liquid sample (5) has been dispensed and a plurality of images of the container volume (13) are recorded.

38. The method according to claim 35, wherein the container volume (13) has a volume from a container bottom (12) to a liquid surface (16) or to an upper boundary (17) offset from the liquid surface (16) by a predetermined distance.

39. The method according to claim 37, wherein the particle (8) is detected using the recorded images and the recorded background images.

40. The method according to claim 36, wherein a height of the particle (8) above a container bottom (12) of the container (3) is determined in the calibration operation.

41. The method according to claim 40, wherein, in the calibration operation, the upper limit (9) is determined as being offset by a predetermined first distance (d1) from the height of the particle and the lower limit (10) is determined as being offset by a predetermined second distance (d2) from the height of the particle (8).

42. The method according to claim 33, wherein a height of the particle (8) above a container bottom (12) of the container (3) is determined in the dispensing operation.

43. The method according to claim 42, wherein the height of the particle (8) is determined after the step of dispensing a liquid sample (5) into the container (3) is performed a predetermined number of times or the height of the particle (8) is determined each time the step of dispensing a liquid sample (5) into the container (3) is performed.

44. The method according to claim 42, wherein presence of the particle (8) in the partial volume region (7) is determined.

45. The method according to claim 44, wherein the calibration operation is initiated again when the particle (8) is not present in the partial volume region (7) or the the partial volume region (7) to be scanned is enlarged when the particle (8) is not present in the partial volume region (7).

46. The method according to claim 33, further comprising determining the number of particles (8) present in the partial volume region (7).

47. The method according to claim 33, wherein a different liquid sample (5) is respectively dispensed into a respective one of multiple containers (3), a position of a particle (8) in the respective container (3) is determined, and the partial volume region (7) is reduced if the particles (8) in the respective containers (3) all have a same position or a position in a predetermined range.

48. A dispensing device (1) comprising: a dispenser (4) operable to dispense a liquid sample (5) into a container (3) containing liquid (2) during a dispensing operation; and a detection device (6) operable to scan a partial volume region (7) of the container (3) to detect a particle (8) located in the liquid sample (5); wherein the detection device (6) is configured to determine an upper limit (9) of the partial volume region (7) and a lower limit (10) of the partial volume region (7) in a calibration operation performed prior to the dispensing operation.

49. The dispensing device (1) according to claim 48, further comprising a control device (11) in communication with the dispenser (4) and the detection device (6), wherein the control device is configured to initiate the dispensing operation by the dispenser (4) and cause the detection device (6) to scan the partial volume region (7) of the container (3).

50. The dispensing device according to claim 48, wherein the detection device (6) is configured to determine a height of the particle (8) above a container bottom (12) of the container (3) in the calibration operation, and wherein the upper limit (9) is offset by a predetermined first distance (d1) from the height of the particle (8) and the lower limit (10) is offset by a predetermined second distance (d2) from the height of the particle (8).

51. The dispensing device (1) according to claim 48, wherein the detection device (6) is configured to check whether the particle (8) is located in the partial volume region (7).

52. The dispensing device (1) according to claim 48, wherein the detection device (6) is configured to determine the number of particles (8) in the partial volume region (7).

Description

BRIEF DESCRIPTION OF THE DRAWING VIEWS

[0039] The subject matter of the disclosure is shown schematically in the figures, wherein elements that are the same or have the same effect are mostly provided with the same reference symbols. In the figures:

[0040] FIG. 1 shows a dispensing device according to the disclosure with a sample carrier with multiple containers,

[0041] FIGS. 2a-2e show a side view of a container to explain the individual steps of the calibration operation,

[0042] FIG. 3 shows a flow chart of a calibration operation and

[0043] FIG. 4 shows a flow chart of a dispensing operation.

DETAILED DESCRIPTION

[0044] A dispensing device 1 shown in FIG. 1 has a dispenser 4 for dispensing a liquid sample 5 into a container 3. In addition, the dispensing device 1 has a detection device 6 for scanning a partial volume region 7 of the container 3 in order to detect a particle 8 located in the liquid sample. The dispensed liquid sample 5 may contain no particle 8, a single particle, or multiple particles. Accordingly, after the liquid sample 5 has been dispensed, the detection device 6 will detect zero particles, a single particle, or multiple particles in the partial volume region 7.

[0045] The container 3 is at least partially filled with a liquid 2. The dispensing device 1 also has a control device 11 which is electrically connected to the dispenser 4 and the detection device 6. The electrical connection is shown with dashed lines in FIG. 1.

[0046] FIG. 1 shows a state at a point in time after a dispensing process has taken place. The dispensed liquid sample 5, which contains a particle 8, has already fallen into the liquid in the container 3. It can be seen from FIG. 1 that the particle 8 is located in the partial volume region 7.

[0047] The detection device 6 has an imaging apparatus, by means of which a large number of images are recorded in the partial volume region 7. As a result, the images depict the partial volume region 7. Since the particle 8 is arranged in the partial volume region 7, the particle 8 can be detected. FIG. 1 shows the image planes in the partial volume region 7, in each of which an image is recorded. The image planes are arranged offset from one another along a spatial direction Z. The spatial direction Z is perpendicular to the container bottom 12. The lower limit 10 of the partial volume region is arranged closer to the container bottom 12 than the upper limit 9 of the partial volume region 7. The partial volume region 7 is arranged offset along the spatial direction Z with respect to the container bottom 12.

[0048] A sample carrier 15, which is a microtiter plate, for example, has multiple containers 3. The dispenser 4 and the sample carrier 15 are each placed in relation to one another in such a way that the dispenser 4 dispenses a liquid sample 5 into the container 3.

[0049] The detection device 6 determines the upper limit 9 and the lower limit 10 of the partial volume region 7 in a calibration operation upstream of (i.e., prior to) the dispensing operation. The calibration operation can be carried out with one container 3 or with several containers 3 of the sample carrier 15. The calibration operation is explained using FIGS. 2a to 2e and the flow chart shown in FIG. 3.

[0050] The calibration operation is initiated in a first step S1. The introduction takes place after a sample carrier 15 containing several containers has been inserted into the dispensing device 1. In particular, the calibration operation can be carried out in a first dispensing process into a container 3 of the sample carrier 15. The subsequent dispensing processes can then be carried out in accordance with the flowchart shown in FIG. 3.

[0051] After initiating the calibration operation in the first step S1, the container bottom 12 and a liquid surface 16 of the liquid 2 in the container 3 are determined in a second step S2. The container bottom 12 can take place by means of an autofocus of the detection device 6. The liquid surface 16 can be determined based on the input from the user of the dispensing device 1 regarding the amount of liquid introduced into the container. In addition, the user can enter a container cross-sectional area, which is also used to determine the liquid surface 16. Alternatively, the container cross-sectional area can be determined automatically. The determination can be made in the evaluation device of the detection device 6. This process is shown in FIG. 2a.

[0052] A container volume 13 can then be scanned in a third step S3. The container volume 13 comprises the entire liquid volume. In addition, the container volume 13 also includes a part that does not contain liquid. An upper limit 17 of the container volume 13 is arranged offset by a predetermined distance from the liquid surface 16 along the spatial direction Z. This state is shown in FIG. 2b. As a result, after the third step S3, there are a large number of background images which show the container without a particle 8.

[0053] Steps S2 and S3 are optional and only serve to determine the position of particle 8 precisely. In other words, the method also works if only steps S4 to S8, which are described in more detail below, are carried out.

[0054] In a fourth step S4, which is shown in FIG. 2c, a liquid sample 5 is dispensed from the dispenser 4. The liquid sample 5 shown has a particle 8. The liquid sample 5 drops into the liquid 2 in the container 2.

[0055] In a fifth step S5, the detection device 6 scans the container volume 13. The container volume 13 preferably has the same volume as the container volume 13 scanned in the third step S3. Alternatively, the container volume 13 can comprise a larger volume. Thus, the container volume 13 can additionally comprise a section that is arranged below the container bottom 12. The detection process is carried out in such a way that the recorded images can be assigned to the previously generated background images. In particular, the position of the individual image planes corresponds to the position of the associated background images.

[0056] Then, in a sixth step S6, the detection device 6 determines the position of the particle 8 in the container 3. In particular, the position of the particle 8 in the spatial direction Z is detected. The distance of the particle 8 from the container bottom 12 along the spatial direction Z can be detected. This state is shown in FIG. 2d. In order to detect the position of the particle 8 in the container 3, the images captured in the fifth step S5 can be compared with the images captured in the third step S3.

[0057] In a seventh step S7, the detection device 6 defines the upper limit 9 and the lower limit 10 on the basis of the determined position of the particle 8. In particular, the detection device determines that the upper limit 9 is arranged offset by a first distance d1 along the spatial direction Z from the particle 8. The lower limit 10 is arranged offset along a spatial direction Z by a second distance d2 from the particle 8. This state is shown in FIG. 2e.

[0058] Thus, after the eighth step S8, the partial volume region 7 is fixed. This partial volume region 7 is scanned in at least some of the dispensing operations of a dispensing operation which follow the calibration operation in time. As already described above, a liquid sample 5 is dispensed in the dispensing operation for the controlled isolation of a specific number of particles.

[0059] FIG. 4 shows a flow chart of the dispensing device 1 in a dispensing operation, the partial volume region 7 having already been determined in a calibration method. In a first step V1 the control device 11 causes a liquid sample 5 to be dispensed through the dispenser 4. The control device 11 notifies the detection device 6 of the dispensing process. In a second step V2, the detection device 6 can start scanning the partial volume region 7 immediately after receiving the information from the control device 11 or after a predetermined time.

[0060] In a third step V3, the detection device 6 detects the number of particles 8 determined in the partial volume region 7. In a fourth step V4, it is checked whether the number of particles 8 located in the partial volume region corresponds to a predetermined number. If this is the case, the position of the particle or particles is determined in a fifth step V5.

[0061] In a sixth step V6, a check is made as to whether the position of the particle 8 corresponds to the positions of particles 8 that were determined in previous dispensing processes, or whether it is within a predetermined range. If this is the case, the partial volume region 7 is reduced in the seventh step V7 and the detection process is ended. The reduced partial volume region 7 is used in subsequent dispensing processes. This means that the detection device 6 scans the reduced partial volume region 7 during subsequent dispensing processes.

[0062] If it is determined in the sixth step V6 that the position of the particle does not match the position of particles from previous dispensing processes, the detection process is ended in an eighth step V8. In subsequent dispensing processes, the same partial volume region 7 is used as in the second step V2. In both the seventh and eighth step, after the detection process has ended, the dispenser 4 and/or sample carrier 15 is moved in such a way that dispensing into another container 3 is possible.

[0063] In the event that it is determined in the fourth step V4 that the number of particles in the partial volume region 7 does not correspond to the specified number of particles, the ninth step V9 checks whether there are more than the specified number of particles 8 in the partial volume region 7 is arranged. If this is the case, the detection process is ended in step V10.

[0064] If it is detected in the ninth step V9 that no particle is arranged in the partial volume region 7, the partial volume region 7 is enlarged in the tenth step V10 and the scanning process is repeated. In this case, the detection device 6 scans the enlarged partial volume region 7 and steps V3 to V9 are repeated.

LIST OF REFERENCE SIGNS

[0065] 1. Dispensing device [0066] 2. Liquid [0067] 3. Container [0068] 4. Dispenser [0069] 5. Liquid sample [0070] 6. Detection device [0071] 7. Partial volume region [0072] 8. Particle [0073] 9. Upper limit [0074] 10. Lower limit [0075] 11. Control device [0076] 12. Container bottom [0077] 13. container volume [0078] 14. Sample carrier [0079] 15. Liquid surface [0080] 16. Upper limit of the container volume [0081] A Distance [0082] Z Spatial direction [0083] d1 First spacing [0084] d2 Second spacing [0085] S1-S8 Method steps in the calibration operation [0086] V1-V10 Method steps in dispensing mode