IMAGE ACQUISITION SYSTEM FOR ACQUIRING AN IMAGE OF A LIQUID SAMPLE

Abstract

The invention relates to an image acquisition system (1) for acquiring an image of a liquid sample (2), comprising a well (3) that stores liquid sample (2), an image acquisition device (4) for acquiring an image of the liquid sample (2) in the well (3), a lid device (5) for covering the well (3) wherein the lid device (5) comprises a lid (6) having a lid part (7) and a lid extension (8) that extends from the lid part (7) into the well (3). The image acquisition system is characterized in that at least one part of the lid extension (8) is in physical contact with the liquid sample (2) when an image is acquired by means of the image acquisition device (4) and a light beam passes through the part of the lid extension (8) that is in physical contact with the liquid sample (2) before it is received by the image acquisition device (4).

Claims

1.-32. (canceled)

33. An image acquisition system for acquiring an image of a liquid sample, comprising: a well that stores the liquid sample; an image acquisition device configured to acquire an image of the liquid sample in the well; and a lid device configured to cover the well, wherein the lid device comprises a lid having a lid part and a lid extension that extends from the lid part into the well; wherein at least one part of the lid extension is in physical contact with the liquid sample when an image is acquired by means of the image acquisition device and the part of the lid extension that is in physical contact with the liquid sample is arranged such that a light beam passes through the part of the lid extension before it is received by the image acquisition device, wherein the lid device comprises a further lid that is connected with the lid such that a space exists between the lid and the further lid.

34. The image acquisition system according to claim 33, wherein the image acquisition system comprises an illumination device configured to provide the light beam.

35. The image acquisition system according to claim 34, wherein: a. the image acquisition device and the illumination device are arranged opposite to each other; or b. the image acquisition device and the illumination device are arranged on the same side of the image acquisition system.

36. The image acquisition system according to claim 33, wherein: a. the image acquisition device is arranged at a predetermined distance from a well bottom; and/or b. the image acquisition device is arranged at a predetermined distance from the part of the lid extension that is in physical contact with the liquid sample; and/or c. the lid part and the lid extension are formed in one piece; and/or d. the lid extension is formed by deep drawing the lid.

37. The image acquisition system according to claim 33, wherein the part of the lid extension is a bottom part of the lid extension.

38. The image acquisition system according to claim 37, wherein: a. the bottom part forms a closed end of the lid extension; and/or b. the bottom part is arranged closer to a well bottom than remaining parts of the lid; and/or c. the bottom part is transparent and/or light transmissive; and/or d. the bottom part and the remaining lid extension are formed in one piece.

39. The image acquisition system according to claim 33, wherein the image acquisition system comprises a plurality of lid devices, wherein the lid devices differ in a length of the lid extension from each other.

40. The image acquisition system according to claim 33, wherein the lid device comprises a plurality of lid extensions.

41. The image acquisition system according to claim 40, wherein: a. the plurality of lid extensions extends from the lid part; and/or b. the number of lid extensions corresponds to the number of wells.

42. The image acquisition system according to claim 33, wherein the image acquisition system comprises a movement device configured to move the well.

43. The image acquisition system according to claim 33, wherein the image acquisition system comprises a sensor for sensing whether the lid extension is in physical contact with the liquid sample.

44. The image acquisition system according to claim 43, wherein: a. the sensor is arranged on the lid extension; and/or b. the sensor is configured to send a sensor signal to a control unit when the sensor is in contact with the liquid sample.

45. The image acquisition system according to claim 33, wherein the further lid comprises an extension tube that extends from a further lid part of the further lid.

46. The image acquisition system according to claim 45, wherein: a. the extension tube surrounds a part of the lid extension; and/or b. the extension tube protrudes longer to the well than the lid extension; and/or c. the extension tube has an open end; and/or d. the extension tube and the further lid part are formed in one piece; and/or e. a plurality of extension tubes extend from the further lid part; and/or f. a number of extension tubes corresponds with a number of wells.

47. The image acquisition system according to claim 33, wherein the image acquisition system comprises a pressure control device, wherein: a. the pressure control device controls a pressure in the space; and/or b. the pressure control device is fluidically connected with the well by the space.

48. The image acquisition system according to claim 47, wherein the pressure control device is configured to create negative pressure in the space before an image is acquired.

49. The image acquisition system according to claim 33, wherein the image acquisition system comprises a control unit.

50. The image acquisition system according to claim 49, wherein: a. the control unit is configured to check whether at least one part of the lid extension is in physical contact with liquid sample; and/or b. the control unit is configured to check whether a sensor measures that the part of the lid extension is in physical contact with liquid sample; and/or c. the control unit determines a negative pressure and acts on a pressure control device to apply negative pressure in the space; and/or d. the control unit is configured to act on the image acquisition device to acquire an image after or during movement of the well by a movement device moves the well; and/or e. the control unit is configured to act on the pressure control device for processing the liquid sample in the well; and/or f. the control unit is configured to act on the image acquisition device to acquire an image after processing of the liquid sample is finished or during the processing of the liquid sample.

51. The image acquisition system according to claim 33, wherein the image acquisition device comprises at least one temperature setting device.

52. The image acquisition system according to claim 51, wherein: a. the image acquisition system comprises a first temperature setting device configured to heat or cool the lid part; or b. the image acquisition system comprises a first temperature setting device configured to heat or cool the lid part, wherein the first temperature setting device comprises at least one through hole; and/or c. the image acquisition system comprises a second temperature setting device configured to heat or cool the well; or d. the image acquisition system comprises a second temperature setting device configured to heat or cool the well and the well is arranged on the second temperature setting device.

Description

[0048] In the figures, the subject-matter of the invention is schematically shown, wherein identical or similarly acting elements are usually provided with the same reference signs.

[0049] FIG. 1: a side view of an image acquisition system according to a first embodiment,

[0050] FIG. 2: a side view of an image acquisition system according to a second embodiment,

[0051] FIG. 3: a side view of an image acquisition system according to a third embodiment,

[0052] FIG. 4: a side view of an image acquisition system according to a fourth embodiment,

[0053] FIG. 5a-e: a processing of the liquid sample and an image taking step with the image acquisition system shown in FIG. 1,

[0054] FIG. 6a-b: a processing of the liquid sample and an image taking step with the image acquisition system shown in FIG. 3,

[0055] FIG. 7a-b: a processing and imaging step with the image acquisition system shown in FIG. 2,

[0056] FIG. 8: a side view of an image acquisition system according to a fifth embodiment,

[0057] FIG. 9: an explosion view of an image acquisition system according to a sixth embodiment,

[0058] FIG. 10: a perspective view of the image acquisition system according to the sixth embodiment,

[0059] FIG. 11: a perspective view of the image acquisition system according to the sixth embodiment comprising a first and second temperature setting device,

[0060] FIG. 12: a side view of the image acquisition system shown in FIG. 11.

[0061] FIG. 1 shows an image acquisition system 1 according to a first embodiment that is used for acquiring an image of a liquid sample 2. The liquid sample 2 is stored in a well 3 of the image acquisition system 1. FIG. 1 shows merely one well 2. However, the image acquisition system 1 can comprise a well carrier 23 that comprises several wells 3 as is shown in FIG. 8. The image acquisition system 1 comprises an image acquisition device 4 for acquiring an image of the liquid sample 2 in the well 3. The image acquisition device can comprise a camera or be a camera. The camera comprises an objective. Additionally, the image acquisition system 1 comprises a lid device 5 for covering the well 3 wherein the lid device 5 comprises a lid 6 having a lid part 7 and a lid extension 8 that extends from the lid part 7 into the well 3. As is shown in FIG. 1 at least one part of the lid extension 8 is in physical contact with the liquid sample 2 when an image is acquired by means of the image acquisition device 4.

[0062] The image acquisition system 1 comprises an illumination device 9 for illuminating a light beam 24. The illumination device 9 and the image acquisition device 4 are arranged opposite to each other with respect to the well 3. In the embodiment shown in FIG. 1 the image acquisition device 4 is arranged below the well 3 and the illumination device 9 is arranged above the well 3. However, in another non-shown embodiment the image acquisition device 4 can be arranged above the well 3 and the illumination device 9 can be arranged below the well 3. The terms above and below refer to a gravitation field.

[0063] The part of the lid extension 8 is formed such that a light beam 24 illuminated by the illumination device 9 passes through it before it is received by the image acquisition device 4. That means, the part of the lid extension 8 is arranged between the illumination device 9 and the image acquisition device 4. The part of the lid extension 8 is a bottom part 11 of the lid extension 8. Said bottom part 11 is arranged nearest to a well bottom 10. The lid extension 8 extends into the well 3. That means, the lid extension 8 is arranged in an inner space 25 surrounded by the well 3 in its circumferential direction.

[0064] The lid device 5 comprises a further lid 13 that is fixedly connected with the lid 6 wherein the further lid 13 and the lid 6 delimit a space 14 between them. The further lid 13 comprises a further lid part 16 and an extension tube 15 extending from the further lid part 16. The extension tube 15 comprises an open end so that liquid sample can enter into the space 14 when the lid device 5 is arranged on the well 3. In the embodiment shown in FIG. 1 negative pressure is applied on the space 14 so that the liquid sample 2 is suctioned into the space 14 such that liquid sample 2 gets into physical contact with the bottom part 11 of the lid extension 8. The extension tube 14, in particular its opening through which liquid sample 2 enters the space 14, is closer to the well bottom 10 than the bottom part 11 of the lid extension 8. Additionally, the extension tube 15 surrounds at least one part of the lid extension 8, in particular the bottom part 11 in the circumferential direction of the lid extension 8. In other words, a part of the lid extension 8, in particular the bottom part 11, is arranged in the extension tube 14. A sensor 12 is attached to the bottom part 11. The sensor 12 detects if the liquid sample 2 is in contact with the bottom part 11.

[0065] FIG. 2 shows a side view of an image acquisition system 1 according to a second embodiment. The image acquisition system 1 according to the second embodiment differs from the image acquisition system 1 according to the first embodiment in the structure of the lid device 1. The lid device 5 merely comprises the lid 6 with the lid part 7 and the lid extension 8. That means, the lid device 5 of the image acquisition system 1 according to the second embodiment does not comprise the further lid 13. The lid extension 8 extends from the lid part 7 so that it is in physical contact with the liquid sample 2.

[0066] Another difference is that the lid extension 8 has a rectangular shape whereas the lid extension 8 shown in FIG. 1 has a tapered shape.

[0067] FIG. 3 shows a side view of an image acquisition system 1 according to a third embodiment. The image acquisition system 1 according to the third embodiment differs from the image acquisition system 1 according to the second embodiment in the length of the lid extension 8. The length of the lid extension 8 of the image acquisition system 1 according to the third embodiment is longer than the length of the lid extension 8 of the image acquisition system 1 according to the second embodiment. This means, the lid extension 8 of the image acquisition system 1 according to the third embodiment extends further in the well 3 than the lid extension 8 of the image acquisition system 1 according to the second embodiment and thus is closer to the well bottom 10 than the lid extension 8 according to the second embodiment.

[0068] FIG. 4 shows a side view of an image acquisition system 1 according to a fourth embodiment. The image acquisition system 1 according to the fourth embodiment differs from the image acquisition system 1 according to the third embodiment in the arrangement of the illumination device 9 and the image acquisition device 4. In particular, in the embodiment shown in FIG. 4 the illumination device 9 is arranged below the well 3 and the image acquisition device 4 is arranged above the well 3.

[0069] FIG. 5a-e show processing of the liquid sample 2 and an image taking step with the image acquisition system 1 shown in FIG. 1. FIG. 5a shows a state of the image acquisition system 1 in which processing is not started. For starting processing of the liquid sample 2 in the well 3 negative pressure is applied in the space 14 as is shown by the arrow. Due to the negative pressure the liquid sample arranged in the extension tube 15 raises. The negative pressure can be set such that the liquid sample does not come into contact with the bottom part 11. This state is shown in FIG. 5b.

[0070] Afterwards, a positive pressure is applied to the space 14. Said pressure leads to that the liquid sample is pushed out of the extension tube 8. This state is shown in FIG. 5c. The aforementioned steps are repeated several times so the liquid sample 2 is processed. Additionally, FIG. 5c shows that a liquid sample drop 32 is arranged on the bottom part 11 of the lid extension. This drop results due to condensing of vaporized liquid sample on the bottom part 11.

[0071] FIG. 5d shows a state of the liquid sample 2 in which at least an image shall be taken by the image acquisition system 1. In said state a negative pressure is applied on the space 14 so that the liquid sample 2 is suctioned in the space 14. The negative pressure is set such that the liquid sample 2 gets into contact with the bottom part 11 of the lid extension 8. The sensor 12 detects that the bottom part 11 is in contact with the liquid sample 2. A control unit receives a sensor signal and acts on the illumination device 9 to illuminate the light beam 24. The light beam 24 passes through an air portion between the illumination device 9 and the bottom part 11, the bottom part 11, the liquid sample 2 and the well bottom 10 before it is received in the image acquisition device 4. The image acquisition device 4 can take one or more images of the liquid sample. In particular, the focal plane of the image acquisition device 4 can be changed so that images in different heights in the well 3 can be acquired.

[0072] After the image or images are acquired, positive pressure can be applied in the space 14 so that the state as shown in FIG. 5e is achieved. Alternatively, ambient pressure can be applied in the space 14 so that the state as shown in FIG. 5a is achieved.

[0073] FIG. 6a-b show processing of the liquid sample 2 and an image taking step with the image acquisition system shown in FIG. 3. In FIG. 6a the liquid sample is processed by rotating the well 3. After said processing step the lid device 5 is attached on the well 3 and one or more images are acquired. The well 3 is not rotated when the image is acquired. The image acquiring occurs identical to the image acquiring discussed above in FIG. 5.

[0074] FIG. 7a-b show processing of the liquid sample and an image taking step with the image acquisition system shown in FIG. 2. In difference to the processing shown in FIGS. 6a and 6b the lid device 5 is attached on well 3 when the well 3 is rotated as is shown in FIG. 7a. Additionally, the well 3 is rotated during the image acquiring as is shown in FIG. 7b.

[0075] FIG. 8 a side view of an image acquisition system 1 according to a fifth embodiment and a well carrier 23. The well carrier 23 comprises a plurality of wells 3. Each of the wells 3 comprises a liquid sample 2. FIG. 8 does not show the illumination device 9 and the image acquisition device 4.

[0076] As is discussed before, the lid device 5 comprises a lid 6 and further lid 13. The further lid part 13 comprises several hollow extension tubes 15 that at partly are arranged in respective wells 3 each of it having a liquid sample 2. The extension tubes 15 extend from further lid part 16 towards the well 3. The lid device 5 also comprises several lid extensions 8 protruding from the lid part 7. The lid extension 8 is partly arranged in the hollow extension tube 15. All lid extensions 8 and extension tubes 15 are identically formed. Additionally, the image acquisition system 1 comprises a first temperature setting device 20 for creating a temperature difference between the temperature of the lid extension 8 and the temperature of a vaporized liquid of the liquid sample 2.

[0077] The lid device 5 comprises a connection part 28 that fluidically connects the space 14 with a pressure control device 18 of the image acquisition system 1. The pressure control device 18 is configured to apply a positive or negative pressure. Due to the fluid connection between the space 14 and the pressure control device 18 by means of the connection part 28, the pressure control device 18 applies a positive or negative pressure on the space 14. By applying negative pressure in the space 14 the liquid sample 2 is aspirated into the extension tube 15 and by applying positive pressure in the space 14 the liquid sample 2 arranged in the extension tube 15 is dispensed into the well 3.

[0078] The lid device 5 is placed on the well carrier 23. As mentioned before, the well carrier 23 comprises a plurality of wells 3 wherein the number of wells 3 corresponds to the number of extension tubes 15. The lid extension 8 and the lid part are a one-piece part. The lid extension 8 has a rectangular shape wherein only a part of the lid extension 8 is arranged in the well 3.

[0079] The first temperature setting device 20 is, in particular directly, arranged on the lid device 5. As the lid extension 8 extends from the lid part 7 towards the well carrier 23 at least the part of the lid extension 8 being arranged in the well 3 has a different temperature than the lid part 7 when the first temperature setting device 20 heats the lid 6. The lid 6 heats gas arranged in the space 14. The first temperature setting device 20 can be a heating plate that covers the lid 6. As the further lid 13 is connected with the lid 6, the further lid 13 is also heated when the lid 6 is heated by the temperature setting device. In said case the further lid 13, in particular the extension tube 15, also heats the vaporized liquid of the liquid sample 2 and thus increases the temperature difference between the lid extension 8 and the vaporized liquid of the liquid sample.

[0080] The image acquisition system 1 comprises a second temperature setting device 22. The second temperature setting device 22 is used to heat the well carrier 3, in particular the liquid samples 2 arranged in the wells 3. The well carrier 3 is arranged on the second temperature setting device 22. In particular, the well carrier 23 is placed on the second temperature setting device 22. The second temperature setting device 22 can be a heating plate. The first temperature setting device 20 and the second temperature setting device 22 can be arranged opposite to each other with regard to the well carrier 23. The second temperature setting device 22 can heat the well carrier 23 and, thus, the liquid sample 2 and the vaporized liquid sample arranged in the well carrier 23.

[0081] The image acquisition system 1 comprises a control unit 19 for controlling the first temperature setting device 20 and the second temperature setting device 22. Alternatively, the first temperature setting device 20 and the second temperature device 22 can be controlled by non-shown different control units 19. The control unit 19 can control the first temperature setting device 20 and the second temperature device 22 such that the lid device 5 and/or the well carrier 23 reach a predetermined temperature. The lid device 5 comprises non-shown temperature sensors for measuring the temperature of the lid 6 and/or the further lid 13 and/or the well carrier 23 and/or the liquid sample 2. The control unit 19 controls the first and/or second temperature setting devices 20, 22 based on the measured temperatures values.

[0082] Additionally, the control unit 19 can control the pressure control device 18. Alternatively, the pressure control device 18 can be controlled by a different control unit. The control unit is electrically or electronically connected with the first temperature setting device 20 and the second temperature setting device 22. Additionally, the control unit is electrically or electronically connected with the pressure control device 18. The electrical connections are shown in dotted lines in FIG. 8 whereas the lid extension 8 shown in FIG. 8 has a rectangular shape.

[0083] FIG. 9 shows an explosion view of an image acquisition system according to a sixth embodiment. The lid device 5 differs from the lid device 5 shown in FIG. 1 in the shape of the lid extension 8. In the embodiment shown in in FIG. 2 the lid extensions 8 have a tapered shape, respectively.

[0084] The lid device 5 comprises a further connection part 29. The further connection part 29 is used to fluidically connect the space 14 with a non-shown measurement device. The measurement device can be a pressure sensor. The pressure sensor measures the pressure within the space 14. Additionally or alternatively, the measurement device can be a temperature sensor for measuring the temperature of the lid 6. The connection part 28 and the further connection part 29 extend from the same lid side 30 in the same direction.

[0085] The lid 6 has a circumferential rim 31. The circumferential rim 31 delimits the space 14 in circumferential direction of the lid device 5. The circumferential rim 31 extends in the same direction as the lid extension 8.

[0086] The lid extensions 8 are arranged in a matrix structure. That means, there exists several rows and columns each having several lid extensions 8. The lid extensions 8 are arranged in distance adjacent to each other. The number and arrangement of the extension tubes 15 is identical to the number and arrangement of the lid extensions 8.

[0087] FIG. 10 shows a perspective view of the image acquisition system according to the sixth embodiment. Said FIG. 10 shows that the lid extensions 8 can be formed by deep drawing the lid 6. Thus, there exist recesses 33 in the locations where the lid extensions 8 are arranged.

[0088] FIG. 11 shows a perspective view of image acquisition system 1 and FIG. 12 shows a side view of the image acquisition system shown in FIG. 11. The first temperature setting device 20 is formed as heating plate and attached to the lid device 5. The first temperature setting device 20 has through holes 21 in the area where the bottom part 11 of the lid extension 8 is arranged. Thus, the heating plate does not cover the bottom part 11. The first temperature setting device 20 comprises a connection portion 26 by means of which it can be connected to other non-shown components of the image acquisition system 1. The lid device 5 is placed on the well carrier 23. The well carrier 23 is arranged on the second temperature setting device 22. The second temperature setting device 22 has an extension 27 that extends in a vertical direction. The extension 27 simplifies the movement of the lid device 5 and the well carrier 23. The second temperature setting device 22 has also non-shown through holes so that the image acquisition device can take an image of the liquid sample 2.

REFERENCE SIGNS

[0089] 1 Image acquisition system [0090] 2 Liquid sample [0091] 3 Well [0092] 4 Image acquisition device [0093] 5 Lid device [0094] 6 Lid [0095] 7 Lid part [0096] 8 Lid extension [0097] 9 Illumination device [0098] 10 Well bottom [0099] 11 Bottom part of the lid extension [0100] 12 Sensor [0101] 13 Further lid [0102] 14 Space [0103] 15 Extension tube [0104] 16 Further lid part [0105] 18 Pressure control device [0106] 19 Control unit [0107] 20 first temperature setting device [0108] 21 through hole [0109] 22 second temperature setting device [0110] 23 well carrier [0111] 24 light beam [0112] 25 inner space [0113] 26 connection portion [0114] 27 extension [0115] 28 connection part [0116] 29 further connection part [0117] 30 lid side [0118] 31 circumferential rim [0119] 32 liquid drop [0120] 33 recess