Cover structure for covering a well plate and automatic processing device including the same

Abstract

A cover structure for covering a well plate is provided. The present invention includes n grooves 11 formed on the top of a cover structure 1, and a positioning structure 12 formed on the top of the cover structure and located inside or outside the grooves, where the value of n is a positive integer, and the positioning structure is adapted to a position 22 of a well in a well plate 2. The present invention further provides an automatic processing device, which includes a sample area for receiving the combination of the cover structure and the well plate, a positioning module for determining the spatial position of the cover structure by the positioning structures of the cover structure, and a mechanical module coupled to the positioning module and having a liquid suction and discharge mechanism.

Description

Technical Field

[0001] The present invention relates to a cover structure for covering a well plate, and particularly to a cover structure and an automatic processing apparatus for dyeing glass plates.

Background Art

[0002] Immunofluorescence (IF) is a technique widely used in the field of biotechnology. It is mainly used to stain biological samples such as cells and tissue slices on a glass plate to detect a predetermined protein in the biological sample and identify its position.

[0003] In the prior art of immunofluorescence staining, it is common to use an open source automatic liquid handling and pipetting apparatus to execute the staining process. For example, the program code of the open source automatic liquid handling and pipetting apparatus is modified so that the system can position different types of well plates, and the glass plate is directly placed at the corresponding position of the well plate, thereby positioning the well plate and staining the glass plate. However, the method of directly placing the glass plate on the well plate lacks consistency in the corresponding positions on the glass plate, making it difficult for the system to accurately complete the staining process and causing a decrease in staining efficiency. Therefore, in this field, there is a need for a cover structure and an automatic processing apparatus including the same that can solve the above problems.

Summary of the Invention

[0004] To solve the above problems, the present invention provides a cover structure for covering a well plate, which includes n grooves formed at the top of the cover structure, and the value of n is a positive integer. The grooves have a positioning structure that is adapted to the positions of the wells in the well plate.

[0005] The present invention further provides an automatic processing apparatus, which includes a sample area, a positioning module, and a mechanical module. The sample area is used to accommodate a combination of a cover structure and a well plate. The positioning module is used to determine the spatial position of the cover structure by the positioning structure of the cover structure. The mechanical module is coupled to the positioning module and includes a liquid suction and discharge mechanism.

Brief Description of the Drawings

[0006]

Figure 1

Figures 2A - 2D

Figure 3

Modes for Carrying Out the Invention

[0007] To describe the embodiments of the present invention in detail, the following examples are provided. Those skilled in the art can easily understand the advantages and effects of the present invention by reading the content disclosed in this specification, and can also implement or apply it in other different embodiments. Each item of the present invention can be variously improved and / or modified without departing from the spirit of the present invention based on different viewpoints and applications, and any requirement or method included within the scope of the present invention can be combined with any other requirement or method disclosed in any specific embodiment of the present invention.

[0008] Unless otherwise specified, the articles "a", "one", "the", and "said" used in this specification refer to the grammatical object of "one or more than one" (i.e., at least one). Also, unless otherwise specified, "or" and "and / or" are interchangeable with each other.

[0009] As used herein, the phrase "at least one" refers to one or more components and should be understood as a phrase meaning at least one component selected from any one or more of the components listed, provided that not all of the listed components are necessarily included at least once, and that any combination of the listed elements is not excluded. This definition encompasses the meaning that components other than those listed in the component list referred to by the phrase "at least one" may exist as necessary, regardless of whether they are related to the components described. Thus, by way of non-limiting example, "at least one of A and B" (or, equivalently, "at least one of A or B", or, equivalently, "at least one of A and / or B") can refer to at least one A in an embodiment, and can also refer to the meaning of more than one A as necessary and no B (and can include components other than B as necessary). In another embodiment, it can refer to at least one B, and can also refer to the meaning of more than one B as necessary and no A (and can include components other than A as necessary). In another embodiment, it can refer to at least one A, and can also refer to the meaning of more than one A as necessary, or can refer to at least one B, and can also refer to the meaning of more than one B as necessary (and can include other components as necessary).

[0010] As used herein, the terms "comprise", "comprised of", "include", "have" and other variations are intended to cover non-exclusive inclusion. For example, when an object is described as "comprising" a certain limiting element, it can further include other components, parts, members, structures, regions, portions, devices, systems, steps or connection relationships, etc., unless otherwise specified, and does not exclude other limiting elements.

[0011] The numerical ranges used in this specification are inclusive and combinable, and any numerical value included in the numerical ranges of this specification can be regarded as the maximum value or the minimum value, from which sub-ranges can be derived. For example, the numerical range "100 mm to 400 mm" includes any sub-ranges between the minimum value of 100 mm and the maximum value of 400 mm, and can include sub-ranges such as 100 mm to 300 mm, 110 mm to 350 mm, 120 mm to 400 mm, etc. Also, if necessary, a plurality of numerical values used in this specification can be selected as the maximum value and the minimum value, thereby deriving a numerical range. For example, the numerical ranges of 100 mm to 127 mm, 127 mm to 400 mm, and 100 mm to 400 mm are derived from the numerical values of 100 mm, 127 mm, and 400 mm.

[0012] The term "about" in the present invention means within the typical tolerance range of the relevant technical field. For example, "about" can be understood as having a difference from the average value of approximately 2 times or less of the standard deviation. When "about" is placed before a series of numbers or ranges, it should be understood that "about" modifies each of the series of numbers or ranges. For example, the numerical values are intended to cover variations of ±20%, ±10%, ±5%, ±1%, ±0.5%, or ±0.1% with respect to the said numerical values. Such variations in numerical values may be caused by various factors, such as measurement errors, experimental errors, manufacturing process errors, or other similar factors. Or, the term "about" means within an acceptable average standard deviation for those skilled in the art. Unless otherwise specified, it should be understood that all numerical ranges, amounts, values, and percentages disclosed in this specification are modified by the term "about" in all situations.

[0013] Terms used to represent positional relationships in space in this invention, such as "upper", "lower" and similar terms, may be used in this specification to describe the relationship between a component / feature and other components / features as shown in the figures. It should be understood that, except for the directions shown in the figures, terms representing positional relationships in space are intended to cover different directions of the component / feature. For example, when a component / feature in the figure is turned upside down, a component described as "below another component / feature" or "under another component / feature" will be defined as "above another component / feature". Therefore, the exemplary term "upper" can include two directions, up and down. Similarly, unless otherwise specified, the terms "upper", "lower" and similar terms are merely for the purpose of description in this specification.

[0014] Unless otherwise specified in this specification, there are no particular restrictions on the manufacturing method of the cover structure, and the related description is merely for explaining the preferred structure of the cover structure. In some embodiments, the cover structure can be manufactured using methods such as additive manufacturing or subtractive manufacturing, but the present invention is not limited thereto.

[0015] In at least one embodiment of the present invention, the cover structure is made of a transparent material or an opaque material.

[0016] In at least one embodiment of the present invention, the value of n may be a positive integer from 1 to 9, for example, 1 to 8, 1 to 7 or 1 to 6, etc., but not limited thereto. In some embodiments, the value of n may be 1, 2, 3, 4, 5, 6, 7, 8 or 9, but the present invention is not limited thereto.

[0017] In at least one embodiment of the present invention, the positioning structure may be a hollow part or a transparent material. In some embodiments, the hollow part may be one or more holes. In some embodiments, the shape of the hole may be circular, elliptical, rectangular, square, diamond-shaped, triangular, or any combination of at least two of them, in part or in whole.

[0018] In at least one embodiment of the present invention, the groove may further have a top opening and a side opening. In some embodiments, the top opening and the side opening can be used to manually and / or automatically place or remove the plate glass.

[0019] In at least one embodiment of the present invention, the groove may be rectangular.

[0020] In at least one embodiment of the present invention, the groove can be used to accommodate the plate glass. In some embodiments, the plate glass may be a slide glass, a cover glass, or a smooth glass.

[0021] In at least one embodiment of the present invention, the plate glass may be coated with a waterproof ring, and the positioning structure can further conform to the waterproof ring.

[0022] The term "waterproof ring" used in the present invention can refer to a closed figure that functions as a hydrophobic barrier and is drawn with a marker pen around a biological sample on the surface of the plate glass. In some embodiments, the shape of the closed figure may be circular, elliptical, rectangular, square, diamond-shaped, triangular, or any combination of at least two of them, in part or in whole.

[0023] In at least one embodiment of the present invention, the combination of the cover structure and the well plate may further include a plate glass having a waterproof ring on its surface, and it is placed in the groove of the cover structure.

[0024] In at least one embodiment of the present invention, the liquid suction and discharge mechanism can be used to suck or discharge the staining solution, and based on the spatial position of the cover structure determined thereby, the staining solution is accurately placed into the waterproof ring.

[0025] In at least one embodiment of the present invention, the cover structure covers the well plate and can be used in various automatic processing devices. Although the present invention uses an automatic processing device and a well plate, the scope of the utility model registration claims of the present invention is not limited to the use of an automatic processing device and a well plate. Those skilled in the art can make various adjustments or changes without departing from the spirit of the present invention, and all of them should be regarded as being included in the protection scope of the present invention. In some embodiments, the automatic processing device may be, but is not limited to, Opentrons, EzMate or Eppendorf epMotion. In some embodiments, the well plate may be, but is not limited to, a 96-well plate, a 60-well plate, a 32-well plate, a 24-well plate, a 12-well plate or a 6-well plate, etc.

[0026] In at least one embodiment of the present invention, the cover structure can have a size applicable to different types of automatic processing devices and well plates.

[0027] In at least one embodiment of the present invention, the length of the cover structure may be about 100 mm to 400 mm, for example, about 105 mm to 350 mm, about 110 mm to 300 mm, about 120 mm to 200 mm, but is not limited thereto. In some embodiments, the length of the cover structure may be about 100 mm, 105 mm, 110 mm, 115 mm, 120 mm, 121 mm, 122 mm, 123 mm, 124 mm, 125 mm, 126 mm, 127 mm, 128 mm, 129 mm, 130 mm, 140 mm, 150 mm, 200 mm, 250 mm, 300 mm, 350 mm or 400 mm, but the present invention is not limited thereto.

[0028] In at least one embodiment of the present invention, the width of the cover structure may be about 80 mm to 90 mm, for example, about 81 mm to 89 mm, about 82 mm to 88 mm, about 83 mm to 87 mm, but is not limited thereto. In some embodiments, the width of the cover structure may be about 80 mm, 81 mm, 82 mm, 83 mm, 84 mm, 85 mm, 86 mm, 87 mm, 88 mm, 89 mm or 90 mm, but the present invention is not limited thereto.

[0029] In at least one embodiment of the present invention, the height of the cover structure may be about 15 mm to 25 mm, for example, about 16 mm to 24 mm, about 17 mm to 23 mm, about 18 mm to 22 mm, but is not limited thereto. In some embodiments, the height of the cover structure may be about 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm or 25 mm, but the present invention is not limited thereto.

[0030] In at least one embodiment of the present invention, when the cover structure is made of a transparent material, the positioning structure may be designed as a positioning point or a hollow portion corresponding to the position of any well in the well plate, and the size of the positioning point or the hollow portion is arbitrary. When the cover structure is made of an opaque material, the positioning structure may be designed as a hollow portion or a transparent material, and the hollow portion or the transparent material has a size greater than or equal to the aperture of the well in the well plate. With the above design, even when the cover structure covers the well plate, the well of the well plate can be visually recognized from above the positioning structure of the cover structure, whereby the positioning module of the automatic processing device can determine the spatial position of the cover structure through the positioning structure of the cover structure and / or the well of the well plate.

[0031] In at least one embodiment of the present invention, the diameter of the positioning structure may be about 5 mm to 15 mm, for example, about 6 mm to 14 mm, about 7 mm to 13 mm, about 8 mm to 12 mm, but is not limited thereto. In some embodiments, the diameter of the positioning structure may be about 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm or 15 mm, but the present invention is not limited thereto.

[0032] In at least one embodiment of the present invention, the groove has a size sufficient to accommodate the plate glass.

[0033] In at least one embodiment of the present invention, the length of the groove may be about 75 mm to 86 mm, for example, about 76 mm to 86 mm, about 77 mm to 85 mm, about 78 mm to 84 mm, but is not limited thereto. In some embodiments, the length of the groove may be about 75 mm, 76 mm, 77 mm, 78 mm, 79 mm, 80 mm, 81 mm, 82 mm, 83 mm, 84 mm, 85 mm or 86 mm, but the present invention is not limited thereto.

[0034] In at least one embodiment of the present invention, the width of the groove may be about 26 mm to 30 mm, for example, about 26 mm to 29.5 mm, about 26.5 mm to 29 mm, about 27 mm to 28.5 mm, but is not limited thereto. In some embodiments, the width of the groove may be about 26 mm, 26.5 mm, 27 mm, 27.5 mm, 28 mm, 28.5 mm, 29 mm, 29.5 mm or 30 mm, but the present invention is not limited thereto.

[0035] In at least one embodiment of the present invention, the height of the groove may be about 0.5 mm to 10 mm, for example, about 1 mm to 9 mm, about 1 mm to 8 mm, about 1 mm to 7 mm, but is not limited thereto. In some embodiments, the height of the groove may be about 0.5 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm or 10 mm, but the present invention is not limited thereto.

[0036] In at least one embodiment of the present invention, the sheet glass may be a common slide glass, having a length of about 75 mm, a width of about 26 mm, and a thickness of about 1 mm.

[0037] In at least one embodiment of the present invention, the groove of the cover structure can be used to accommodate a plurality of sheet glasses coated with a waterproof ring, thereby arranging these sheet glasses regularly and improving the consistency of corresponding positions in the sheet glasses. The present invention is designed such that the positioning structure of the cover structure, the wells of the well plate, and / or the waterproof rings on the sheet glasses are compatible with each other, enabling high-precision positioning and an efficient staining process. Furthermore, the cover structure of the present invention can be designed to be compatible with different types of automatic processing devices and well plates, and thus can be widely applied to any field where it is necessary to stain samples of sheet glass.

[0038] Exemplary embodiments of the present invention will be further described below, which are not intended to limit the scope of the present invention. Those skilled in the art can make various adjustments and modifications without departing from the spirit and scope of the present invention.

[0039] Embodiment

[0040] Referring to FIG. 1, FIG. 1 is a schematic diagram of a cover structure according to at least one embodiment of the present invention.

[0041] As shown in FIG. 1, the cover structure 1 for covering the well plate in the present invention can include three grooves 11. The grooves 11 are all formed at the top of the cover structure 1. Each of the grooves 11 has a positioning structure 12, a top opening 13, and a side opening 14. In some embodiments, the cover structure 1 may be made of an opaque material, and the positioning structure 12 may be a single circular hole, but the present invention is not limited thereto.

[0042] Referring to FIGS. 2A to 2D, FIGS. 2A to 2D are schematic views of the usage modes of the cover structure based on at least one embodiment of the present invention.

[0043] As shown in FIG. 2A, the cover structure 1 covers the well plate 2 from above. The well plate 2 includes a plurality of wells 22, and the three positioning structures 12 of the cover structure 1 respectively conform to the positions of the three wells 22. In some embodiments, the well plate 2 may be a 96-well plate, but the present invention is not limited thereto.

[0044] As shown in FIG. 2B, the cover structure 1 covers the well plate 2. By disposing three plate glasses 3 coated with a waterproof ring 31 from the top opening 13 and / or the side opening 14 of the cover structure 1 into the three grooves 11 respectively, a combination of the cover structure 1, the well plate 2, and the plate glass 3 can be obtained. Here, the plate glasses 3 are regularly arranged, and the three positioning structures 12 respectively conform to the positions of the three waterproof rings 31. The waterproof ring 31 can surround a biological sample (not shown) as a hydrophobic barrier.

[0045] As shown in FIG. 2C, the combination of the cover structure 1, the well plate 2, and the plate glass 3 is disposed in an automatic processing device 4. In some embodiments, the automatic processing device 4 may be Opentrons, but is not limited thereto. It includes a sample area 41, a positioning module (not shown), a mechanical module 42, and a staining solution storage area 43. The mechanical module 42 can be coupled to the positioning module and includes a liquid suction and discharge mechanism 421. The positioning module determines the spatial position of the cover structure 1 through the positioning structure 12 of the cover structure 1 by executing a modified program code, so that the position of the liquid suction and discharge mechanism 421 can be aligned with the combination of the cover structure 1 and the well plate 2 accommodated in the sample area 41 and the position of the waterproof ring 31 on the surface of the plate glass 3 disposed on the cover structure 1.

[0046] As shown in step S101 of FIG. 2D, the mechanical module 42 sucks the staining solution from the staining solution storage area 43 through the liquid suction and discharge mechanism 421. Subsequently, as shown in step S102 of FIG. 2D, the mechanical module 42 is moved to the position where the combination of the cover structure 1, the well plate 2, and the cover glass 3 in the sample area 41 is arranged. The liquid suction and discharge mechanism 421 aligns with the position of the waterproof ring 31 based on the determined spatial position of the cover structure, and discharges the staining solution into the waterproof ring 31 to stain the cover glass 3, thereby obtaining a stained biological sample.

[0047] Comparative Example

[0048] Referring to FIG. 3, FIG. 3 is a schematic diagram of the usage state of a well plate based on at least one comparative example of the present invention. As shown in FIG. 3, the cover glass 3 is directly placed on the well plate 2 to obtain a combination of the well plate 2 and the cover glass 3. In some comparative examples, the combination of the well plate 2 and the cover glass 3 is placed in the automatic processing device 4 in FIG. 2C, and further, the liquid suction and discharge mechanism 421 of the mechanical module 42 in FIG. 2D is used to suck the staining solution from the staining solution storage area 43. Subsequently, the mechanical module 42 is moved to the position where the combination of the well plate 2 and the cover glass 3 in the sample area 41 is arranged. The position of the liquid suction and discharge mechanism 421 is aligned with the position of the well 22 of the well plate 2, and the staining solution is discharged to the position of the well 22. However, since the cover glass 3 is irregularly arranged on the well plate 2, the position of the waterproof ring 31 does not coincide with the position of the well 22, and the liquid suction and discharge mechanism 421 cannot align with the waterproof ring 31 through the well 22. As a result, the staining solution cannot be accurately discharged into the waterproof ring 31. Therefore, in order for the user to obtain a stained biological sample, it is necessary to spend a lot of time adjusting the position of the cover glass 3.

[0049] As can be seen from the above, by fixing the plate glass using the cover structure of the present invention, the consistency of the corresponding positions in the plate glass can be improved, and the accuracy and processing efficiency of the dyeing process can be enhanced. Further, the cover structure of the present invention can be manufactured to meet the needs of different types of automatic processing devices and well plates, and thereby can be widely applied to all fields where it is necessary to dye samples of plate glass.

[0050] The embodiments described above are only some embodiments of the present invention, and any equivalent modifications and changes made within the scope of the claims of the present invention are all included in the scope covered by the present invention.

Explanation of Reference Numerals

[0051] 1: Cover structure 11: Groove 12: Positioning structure 13: Top opening 14: Side opening 2: Well plate 22: Well 3: Plate glass 31: Waterproof ring 4: Automatic processing device 41: Sample area 42: Mechanical module 421: Liquid suction and discharge mechanism 43: Dyeing solution storage area S101, S102: Step

Claims

1. A cover structure for covering a well plate, n grooves formed on a top portion of the cover structure; a positioning structure formed on a top of the cover structure and located inside or outside the groove; and the value of n is a positive integer, and the positioning structure is adapted to the position of a well in the well plate. Cover structure.

2. The cover structure of claim 1 , wherein the value of n is a positive integer from 1 to 9.

3. The cover structure of claim 1 , wherein the positioning structure is a hollow portion or a transparent material.

4. The cover construction of claim 1 , wherein the channel further comprises a top opening and a side opening.

5. The cover structure of claim 1 , wherein the groove is rectangular.

6. The cover structure of claim 1 , wherein the groove is adapted to receive a glass sheet.

7. 7. The cover structure of claim 6, wherein the glass sheet is coated with a waterproof ring, and the positioning structure further accommodates the waterproof ring.

8. a sample area for receiving the combination of the cover structure and the well plate according to claim 1; a positioning module for determining a spatial position of the cover structure by the positioning structure of the cover structure; a mechanical module coupled to the positioning module and having a liquid aspirating and dispensing mechanism for positioning the cover structure and well plate combination.

9. The combination of the cover structure and the well plate further includes a glass plate having a waterproof ring on a surface thereof, which is disposed in the groove of the cover structure; 9. The device according to claim 8, wherein the liquid suction and discharge mechanism is used to suction or discharge staining liquid, and to accurately place staining liquid into the waterproof ring based on the determined spatial position of the cover structure.

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