Solution handling guide device and solution handling method using same

Abstract

The present invention provides: a solution handling guide device that can be detached from or attached to a plate in which a plurality of wells are spaced apart from each other, wherein a solution required for various experiments or the like can be injected into the wells via through-holes or extracted from the wells; and a solution handling method using same. The solution handling guide device that can be detached from or attached to a plate in which a plurality of wells are spaced apart from each other and a central space is formed between the plurality of wells according to an embodiment of the present invention comprises: a substrate that has a certain thickness and can be detached from or attached to the plate; and a plurality of main guide units which are spaced apart from each other on the substrate, are respectively fastened to the upper portions of the plurality of wells, and have first through-holes formed therein. Also, the solution handling method using the solution handling guide device according to an embodiment of the present invention comprises: preparing the solution handling guide device and a plate in which a plurality of wells are spaced apart from each other and a central space is formed between the plurality of wells; fastening the solution handling guide device to the upper portion of the plate; and handling solutions in the first through-holes using the solution handling guide device.

Description

Solution handling guide device and solution handling method using the same

[0001] The present invention relates to a solution handling guide device and a solution handling method using the same, and more particularly, to a solution handling guide device that is detachable from a plate in which a plurality of wells are spaced apart, and can inject solutions required for various experiments into the wells through through holes or extract solutions from the wells, and a solution handling method using the same.

[0002] Recently, interest in and research on cell culture have been increasing as the use of cultured cells in disease treatment has expanded. Cell culture is a technology that extracts cells from living organisms and cultivates them ex vivo. Cultured cells can be differentiated into various tissues of the body, such as skin, organs, and nerves, and then transplanted into the human body. Alternatively, they can be transplanted into the human body in a pre-differentiated state, allowing simultaneous engraftment and differentiation, enabling their use in the treatment of various diseases.

[0003] Additionally, as interest in alternative animal testing methods that utilize cells without using animals increases in the process of developing new drugs used to treat diseases, the demand for customized cell culture cultureware and electrode plates is increasing.

[0004] In the past, when placing cells at the exact center of the inner surface of a well of a cell culture cultureware or cell culture plate, or conducting protein experiments, etc., the worker would open the outer blocking door of the sterilization workbench and work while looking inside the well while exposed to contaminants, or work in an external experimental environment, making the worker vulnerable to a contaminated environment.

[0005] In addition, injecting a small amount of solution, such as 1 to 50 μL, into the center of a well is dependent on the operator's operating ability, as even an experienced technician may have to try several times to succeed, and there may be significant deviations in the injection location depending on the operator performing the experiment.

[0006] In addition, when handling cell culture media or solutions, a pipette is used to inject the solution, but in many cases, the pipette tip is attached to the well wall and the solution is injected or removed. In this case, sensitive cells are stressed by the fluid flow and pressure and fall off, or cells in a suspended state that are dividing during cell growth are sucked, causing cell culture deviations between wells.

[0007] Meanwhile, when cells are made into 3D spheroids, the spheroid size is determined by controlling the amount of culture solution and cell concentration. The total amount of each cell droplet is 15 to 30 ㎕, and each cell culture solution droplet contains approximately 300 to 3000 cells / ㎕. At this time, when controlling the 15 to 30 ㎕ solution, injection technology assistance is required to position it at the exact center of the surface of the culture dish well.

[0008] The technical problem to be solved by the present invention is to provide a solution handling guide device and a solution handling method using the same, in which a substrate is mounted on a plate on which a plurality of wells are spaced apart, a main guide unit having a through hole formed on the substrate is fastened to the plate, and the through hole of the main guide unit is positioned at the upper part of the well, so that a solution is handled at the exact center of the well by the main guide unit, making work convenient, and minimizing deviation in the culture position to improve culture efficiency.

[0009] The technical problems of the present invention are not limited to the technical problems mentioned above, and other technical problems not mentioned will be clearly understood by those skilled in the art from the description below.

[0010] According to one embodiment of the present invention for achieving the above technical task, a detachable solution handling guide device is provided on a plate in which a plurality of wells are spaced apart from each other and a central space is formed between the plurality of wells, and may include a substrate that is detachably provided on the plate and has a predetermined thickness, and a plurality of main guide units that are spaced apart from each other on the substrate and are each fastened to an upper portion of the plurality of wells, and have first through holes formed therein.

[0011] At this time, the substrate may be formed such that one side is formed in a step or slope shape, so that the width of the upper part is wider than the width of the lower part.

[0012] Additionally, the main guide unit may include a first protrusion formed protrudingly on the upper surface of the substrate and a concave portion formed concavely on the lower surface of the substrate.

[0013] Meanwhile, the concave portion can be fastened to the upper portion of the well.

[0014] In addition, the first through hole may include a first opening formed in the first protrusion, a second opening formed in the concave portion, and an inner wall extending between the first opening and the second opening.

[0015] At this time, the width may become narrower as it moves from the first opening to the second opening.

[0016] Additionally, the ratio of the diameter (r1) of the first opening to the diameter (r2) of the second opening may be 12 to 8.

[0017] Additionally, the inclination angle of the inner wall may be 5 to 85 degrees.

[0018] In addition, the height (h1) of the first protrusion and the diameter (r1) of the first opening can satisfy the following equation 1.

[0019] 0≤h1 / r1≤55e.......(1)

[0020] The height (h1) of the first protrusion and the depth (d1) of the concave portion can satisfy the following equation 2.

[0021] 0≤h1 / d1≤10e.......(2)

[0022] And, it may include at least one sub-guide unit disposed between the plurality of main guide units and inserted into the central space.

[0023] In addition, the sub-guide unit includes a second protrusion formed convexly on the lower surface of the substrate, and the second protrusion can be fastened to the central space.

[0024] At this time, the height (h2) of the second protrusion may be greater than 0 and less than 21 mm.

[0025] Meanwhile, the sub-guide unit may be formed with a second through hole penetrating the second protrusion.

[0026] A solution handling method using a solution handling guide device according to one embodiment of the present invention may include a step of preparing a plate in which a solution handling guide device and a plurality of wells are spaced apart from each other and a central space is formed between the plurality of wells, a step of fastening the solution handling guide device to an upper portion of the plate, and a step of handling a solution in the first through-hole using the solution handling guide device.

[0027] According to the present invention as described above, a substrate is detachably provided on a plate in which a plurality of wells are spaced apart, a main guide unit is disposed on the substrate, and a through hole formed in the main guide unit is positioned at the upper part of the well, so that a solution is handled to the exact center of the well through the through hole, so that even a non-skilled worker can easily work, thereby improving convenience and efficiency of work, and minimizing deviation in the culture position, thereby improving culture efficiency.

[0028] The effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description below.

[0029] FIG. 1 is a perspective view illustrating a solution handling guide device according to Example 1 of the present invention.

[0030] Figure 2 is a front view illustrating a solution handling guide device according to Example 1 of the present invention.

[0031] Figure 3 is a plan view illustrating a solution handling guide device according to Example 1 of the present invention.

[0032] Figure 4 is a cross-sectional view illustrating a solution handling guide device according to Example 1 of the present invention.

[0033] FIG. 5 is a cross-sectional view illustrating the main guide unit of the solution handling guide device according to Example 1 of the present invention.

[0034] Figure 6 is an exploded perspective view of a solution handling guide device according to Example 1 of the present invention being installed on a plate.

[0035] Figure 7 is a cross-sectional view showing a state in which a solution handling guide device according to Example 1 of the present invention is installed on a plate.

[0036] Figure 8 is a perspective view illustrating a solution handling guide device according to Example 2 of the present invention.

[0037] Figure 9 is a cross-sectional view illustrating a solution handling guide device according to Example 2 of the present invention.

[0038] Fig. 10 is a bottom perspective view illustrating a solution handling guide device according to Example 3 of the present invention.

[0039] Fig. 11 is a cross-sectional view illustrating a solution handling guide device according to Example 3 of the present invention.

[0040] Fig. 12 is a bottom perspective view illustrating a solution handling guide device according to Example 4 of the present invention.

[0041] Fig. 13 is a cross-sectional view illustrating a solution handling guide device according to Example 4 of the present invention.

[0042] Figure 14 is an exemplary diagram illustrating a method for evaluating a solution center injection deviation according to one embodiment of the present invention.

[0043] Figure 15 is a flowchart illustrating a solution handling method using a solution handling guide device according to an embodiment of the present invention.

[0044] The advantages and features of the present invention, and the methods for achieving them, will become clearer with reference to the embodiments described in detail below together with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below, but may be implemented in various different forms. These embodiments are provided only to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims. Accordingly, in some embodiments, well-known process steps, well-known device structures, and well-known techniques are not specifically described to avoid ambiguity in the interpretation of the present invention. Like reference numerals refer to like elements throughout the specification.

[0045] Spatially relative terms such as "below," "beneath," "lower," "above," and "upper" may be used to readily describe the relationship of one element or component to another, as illustrated in the drawings. Spatially relative terms should be understood to encompass different orientations of the elements during use or operation in addition to the orientation depicted in the drawings. For example, if an element depicted in the drawings were flipped over, an element described as "below" or "beneath" another element could end up "above" the other element. Thus, the exemplary term "below" could encompass both the above and below orientations. Elements may also be oriented in other directions, and thus spatially relative terms may be interpreted accordingly.

[0046] The terminology used herein is for the purpose of describing embodiments only and is not intended to limit the present invention. In this specification, the singular also includes the plural unless the context clearly dictates otherwise. As used herein, the terms "comprises" and / or "comprising" do not exclude the presence or addition of one or more other components, steps, operations, and / or elements.

[0047] Unless otherwise defined, all terms (including technical and scientific terms) used herein may be used in their common sense to those of ordinary skill in the art to which the present invention pertains. Furthermore, terms defined in commonly used dictionaries are not to be interpreted ideally or excessively unless explicitly and specifically defined otherwise.

[0048] FIG. 1 is a perspective view illustrating a solution handling guide device according to Embodiment 1 of the present invention, FIG. 2 is a front view illustrating a solution handling guide device according to Embodiment 1 of the present invention, FIG. 3 is a plan view illustrating a solution handling guide device according to Embodiment 1 of the present invention, FIG. 4 is a cross-sectional view illustrating a solution handling guide device according to Embodiment 1 of the present invention, FIG. 5 is a cross-sectional view illustrating a main guide unit of a solution handling guide device according to Embodiment 1 of the present invention, FIG. 6 is an exploded perspective view illustrating a solution handling guide device according to Embodiment 1 of the present invention for installation on a plate, FIG. 7 is a cross-sectional view illustrating an installation state of a solution handling guide device according to Embodiment 1 of the present invention, FIG. 8 is a perspective view illustrating a solution handling guide device according to Embodiment 2 of the present invention, FIG. 9 is a cross-sectional view illustrating a solution handling guide device according to Embodiment 2 of the present invention, FIG. 10 is a bottom perspective view illustrating a solution handling guide device according to Embodiment 3 of the present invention, and FIG. 11 is a cross-sectional view illustrating a solution handling guide device according to Embodiment 3 of the present invention. This is a cross-sectional view illustrating a solution handling guide device, FIG. 12 is a bottom perspective view illustrating a solution handling guide device according to Example 4 of the present invention, FIG. 13 is a cross-sectional view illustrating a solution handling guide device according to Example 4 of the present invention, FIG. 14 is an exemplary view for explaining a solution center injection deviation evaluation method according to an embodiment of the present invention, and FIG. 15 is a flowchart illustrating a solution handling method using a solution handling guide device according to an embodiment of the present invention.

[0049]

[0050] As illustrated in FIGS. 1 to 13, a solution handling guide device according to one embodiment of the present invention may include a substrate (100) detachably mounted on a plate (10) having a plurality of wells (20) spaced apart from each other, and a main guide unit (200) spaced apart from each other on the substrate (100).

[0051] Referring to FIGS. 6 and 7, the plate (10) on which the solution handling guide device of the present invention is installed serves as a cell culture body and may be a flat plate, typically in the shape of a rectangular parallelepiped. Furthermore, the plate (10) is preferably made of a biocompatible material. Although not particularly limited, it may be made of, for example, a transparent biocompatible plastic such as PDMS, PMMA, PET, or PC, glass, or the like.

[0052] In addition, the wells (20) may be arranged in a plurality of rows (horizontal) and columns (vertical) at preset intervals on one side of the plate (10). At this time, the number of the wells (20) may be variously determined, such as 4, 6, 12, 16, 24, 96, 128, etc. In the attached drawing, the number of wells (20) is set to 16, but is not limited thereto.

[0053] Additionally, the well (20) may be open at the top and sunken to a predetermined depth to form a bottom and sidewalls. A solution for cell culture may be handled in the well (20). Meanwhile, "handling" refers to a concept encompassing the injection or extraction of a solution into the well (20).

[0054] Although not shown, a surface treatment layer that prevents cell fixation or a protein surface treatment layer for cell fixation may be formed on the surface of the well (20) depending on the intended use.

[0055] Meanwhile, the plate (10) may have a central space (30) formed between a plurality of wells (20).

[0056] The above substrate (100) can be detachably attached to the upper part of the plate (10).

[0057] In addition, the substrate (100) has a certain thickness, and as illustrated in FIG. 7, etc., one or both sides of the substrate (100) may be formed in a stepped or inclined shape so that the width of the upper side is wider than the width of the lower side. Accordingly, in the process of separating the substrate (100) from the plate (10), an operation of pressing one end of the substrate (100) downward and lifting the other end can be smoothly performed, and as a result, the convenience and safety of the process of separating the substrate (100) from the plate (10) can be improved.

[0058] In addition, in the process of separating the substrate (100) from the plate (10), the phenomenon of the solution injected into the well (20) being released to the outside or the cells adsorbed to the well (20) being detached can be prevented, and the phenomenon of external contaminants being introduced into the well (20) can also be prevented.

[0059] Meanwhile, the substrate (100) may be formed to match the horizontal (row) x vertical (column) width of the plate (1), or may be formed to be small or large.

[0060] The above main guide units (200) may be spaced apart from each other on the substrate (100) and may be respectively fastened to the upper portions of a plurality of wells (20). In addition, the main guide units (200) may be arranged in a plurality of rows (horizontal) and columns (vertical) on the substrate (100). For example, as shown in FIG. 1, 16 main guide units (200) may be arranged side by side in 2 rows (horizontal) and 8 columns (vertical) on the substrate (100). However, the number of rows and columns in which the main guide units (200) are arranged is not particularly limited.

[0061]

[0062] Example 1.

[0063] Referring to FIGS. 1 to 7, the main guide unit (200) may include a first protrusion (210) formed to protrude on the upper surface of the substrate (100) and a concave portion (220) formed to be concave on the lower surface of the substrate (100).

[0064] Referring to FIGS. 4 and 5, the main guide unit (200) may have a first through hole (230) formed therein for handling a solution as a well (20). At this time, the first through hole (230) may be formed by penetrating the first protrusion (210) and the concave portion (220).

[0065] In addition, referring to FIG. 5, the first through hole (230) may include a first opening (231) formed in the first protrusion (210), a second opening (232) formed in the concave portion (220), and an inner wall (233) extending between the first opening (231) and the second opening (232).

[0066] At this time, the inner wall (233) may become narrower in width from the first opening (231) toward the second opening (232). Meanwhile, the inclination angle (θ) of the inner wall (233) may be 5 to 85 degrees. Accordingly, the solution passing through the first through hole (230) may be injected into the exact center position of the well (20). Meanwhile, if the inclination angle (θ) of the inner wall (233) is less than 5 degrees, a problem of loss of function of the inner wall (233) of the main guide unit (200) occurs, and if it exceeds 85 degrees, the first opening (231) and the second opening (232) lose the sealing function of the finet tip having an inclination angle of approximately 85 degrees, resulting in a problem of injection deviation from the exact center position.

[0067] Results of the experiment evaluating the deviation of the injection of the solution at the center according to one embodiment of the present invention Inner wall angle 5 degrees 84 degrees 90 degrees Minimum inner wall thickness according to the inner wall angle 0.189 mm 2 mm 2 mm Maximum inner wall thickness according to the inner wall angle 1.811 mm 2 mm 2 mm Maximum distance between the end of the second through hole and the pipette tip according to the maximum driving angle 0.5007 mm 0.079 mm 0.3163 mm Injection deviation distance (d) based on the center 1.042 ± 0.25 mm 0.9 ± 0.05 mm 0.1184 ± 0.24 mm Degree of pipette tip shaking according to the inner wall angle Up, down, up

[0068] The above shaking levels are high; meaning a lot of shaking, medium; meaning shaking, and low; meaning no shaking.

[0069] FIG. 14 is an exemplary diagram showing the degree of pipette tip injection clearance and the degree of center deviation according to the maximum inner wall thickness when the inner wall (233) has an inclination angle of 5 degrees, for example. As shown in FIG. 14 and Table 1, as the pipette tip (1) is fixed while being in close contact with the inner wall (233), the end of the pipette tip (1) can be positioned at the center of the well (20). At this time, the end of the pipette tip (1) can be spaced apart from the upper surface and the side wall of the well (20) by a predetermined interval. Accordingly, the solution injected into the well (20) through the pipette tip (1) can be positioned close to the center of the well (20), and also, the solution injected into the well (20) can be prevented from contacting the side wall of the well (20).

[0070] In addition, the ratio of the diameter (r1) of the first opening (231) to the diameter (r2) of the second opening (232) may be 12 to 8. If it is less than 12, the end of the pipette tip (1) cannot pass through the first through hole (230), which causes a problem of use restriction, and if it is more than 8, the end of the pipette tip (1) has a problem of fixing the pipette tip (1) due to the step of the concave portion (220) between the first opening (231) and the second opening (232).

[0071] Evaluation experiment results for fixing the pipette tip (1) by passing the end through the first through-hole (230) according to the type of pipette tip (1) according to one embodiment of the present invention Diameter ratio less than 1.2 Diameter ratio more than 8 Pipette tip type Blue TipYellow TipWhite TipBlue TipYellow TipWhite TipInjectable capacity 100~1000㎕20~200㎕0.5~10㎕100~1000㎕20~200㎕0.5~10㎕Pipette tip end diameter 1mm0.8mm0.3mm1mm0.8mm0.3mmPass through the first through-holeNoNoNoNoPassPassPassPassPresence of fixation of target positionNoNoNoNoNoNoNoNoShaking degree Confirm NoConfirm NoConfirm NoImaginableImaginable

[0072] The height (h1) of the first protrusion (210) and the diameter (r1) of the first opening (231) can satisfy the following equation 1.

[0073] 0≤h1 / r1≤55e.....(1)

[0074] And, the height (h1) of the first protrusion (210) and the depth (d1) of the concave portion (220) can satisfy the following equation 2.

[0075] 0≤h1 / d1≤10e.....(2)

[0076] Accordingly, the pipette tip (1) used for solution injection and extraction can be stably attached to the first protrusion (210), and the pipette tip (1) can be guided so as not to touch the bottom surface of the well (20).

[0077] At this time, e represents the thickness of the main guide unit (200), including the height (h1) of the first protrusion (210) and the depth (d1) of the concave portion (220).

[0078]

[0079] Example 2.

[0080] Referring to FIGS. 8 and 9, the main guide unit (200) may not have a first protrusion (210) protruding from the upper surface of the substrate (100) as in Example 1, but may have a concave portion (220) formed concavely on the lower surface of the substrate (100). In addition, a first through hole (230) may be formed to handle a solution by penetrating the substrate (100) and the concave portion (220).

[0081]

[0082] Example 3.

[0083] Referring to FIGS. 10 and 11, the sub-guide unit (300) may be disposed between the main guide units (200). That is, the sub-guide unit (300) may be disposed between a plurality of main guide units (200) and inserted into the central space (30) of the plate (10). In addition, the sub-guide unit (300) may be formed in at least one or more numbers.

[0084] Referring to Fig. 10, the sub-guide unit (300) may include a second protrusion (310) formed convexly on the lower surface of the substrate (100). The second protrusion (310) may be fastened to the central space (30) of the plate (10). Meanwhile, the outer shape of the central space (30) of the plate (10) and the second protrusion (310) may be formed in a diamond shape.

[0085] In addition, the height (h2) of the second protrusion (310) may be formed to be approximately greater than 0 and less than 21 mm. Accordingly, when the second protrusion (310) is fastened to the central space (30) of the plate (10), the stability of fastening may be improved.

[0086]

[0087] Example 4.

[0088] Referring to FIGS. 12 and 13, the sub-guide unit (300) may be formed with a second through-hole (320) penetrating the second protrusion (310). Accordingly, additional solution may be injected through the second through-hole (320) to prevent solution evaporation.

[0089] As shown in Fig. 15, the solution handling method using the solution handling guide device according to embodiments of the present invention first prepares a plate (10) in which a central space (30) is formed between a plurality of wells (20). (S100)

[0090] In addition, a solution handling guide device is placed on the upper portion of the plate (1) at a distance from a plurality of wells (20).

[0091] And, a solution handling guide device is fastened to the upper portion of the plate (10). (S200) At this time, the concave portion (220) of the main guide unit (200) can be connected to the well (20). That is, the interior of the well (20) where the solution is handled and the first through hole (230) are connected.

[0092] Afterwards, when the solution handling guide device is fastened to the plate (10), the solution is handled into the well (20) through the first through hole (230) using the solution handling guide device. (S300) Meanwhile, as the inner wall (233) of the first through hole (230) becomes narrower in the direction from the first opening (231) to the second opening (232), the solution passing through the first through hole (230) can be positioned at the exact center of the well (20).

[0093] As described above, the present invention connects a solution handling guide device to the upper portion of a plate (10) in which a plurality of wells (20) in which a solution is handled are formed, and the first through-hole (230) of the main guide unit (200) is connected to the inside of the well (20), thereby handling the solution into the well (20) using the solution handling guide device, thereby minimizing exposure to external contaminants and preventing contamination of the solution.

[0094] In addition, since the inner wall (233) of the first through hole (230) is formed to become narrower as it goes toward the well (20), the solution injected through the first through hole (230) is positioned at the exact center of the well (20), making it easy to handle the solution even for non-skilled technicians, and minimizing deviation in the culture position so that re-experimentation is not required and culture efficiency can be increased.

[0095] And, when the solution handling guide device is fastened on the plate (10), the second protrusion (310) formed convexly of the sub-guide unit (300) is inserted into the central space (30) formed between the wells (20) of the plate (10), so that the first through-hole (230) is naturally positioned in the well (20) as the second protrusion (310) is inserted into the central space (30), making it convenient to handle the solution.

[0096] The embodiments of the present invention described above are merely exemplary, and the scope of protection of the present invention may include various modifications and equivalent examples thereof by a person having ordinary skill in the art of the present invention.

Claims

1. In a detachable solution handling guide device on a plate in which a plurality of wells are spaced apart from each other and a central space is formed between the plurality of wells, a substrate having a certain thickness; and A plurality of main guide units spaced apart from each other on the substrate and each fastened to the upper portion of the plurality of wells, and having a first through hole formed therein; A solution handling guide device including:

2. In claim 1, The above substrate is a solution handling guide device characterized in that one side is formed in a stepped or inclined shape, and the width of the upper part is wider than the width of the lower part.

3. In claim 1, The above main guide unit includes a first protrusion formed protrudingly on the upper surface of the substrate and a concave portion formed concavely on the lower surface of the substrate, A solution handling guide device characterized in that the above concave portion is fastened to the upper portion of the well.

4. In claim 1 or claim 3, The first through hole includes a first opening formed in the first protrusion, a second opening formed in the concave portion, and an inner wall extending between the first opening and the second opening, A solution handling guide device characterized in that the width becomes narrower as it goes from the first opening toward the second opening.

5. In claim 4, A solution handling guide device, characterized in that the ratio of the diameter (r1) of the first opening to the diameter (r2) of the second opening is 1.2 to 8.

6. In claim 4, A solution handling guide device characterized in that the angle of inclination of the inner wall is 5 to 85 degrees.

7. In claim 4, The height (h1) of the first protrusion and the diameter (r1) of the first opening satisfy the following equation 1, A solution handling guide device characterized in that the height (h1) of the first protrusion and the depth (d1) of the concave portion satisfy the following equation 2. 0≤h1 / r1≤55e......(1) 0≤h1 / d1≤10e......(2) 8. In claim 1, A solution handling guide device further comprising at least one sub-guide unit disposed between the plurality of main guide units and inserted into the central space.

9. In claim 8, The above sub-guide unit includes a second protrusion formed convexly on the lower surface of the substrate, A solution handling guide device characterized in that the second protrusion is fastened to the central space.

10. In claim 9, A solution handling guide device characterized in that the height (h2) of the second protrusion is greater than 0 and less than 21 mm.

11. In claim 9, A solution handling guide device characterized in that the above sub-guide unit has a second through-hole formed therein that penetrates the second protrusion.

12. A step of preparing a solution handling guide device of claim 1 and a plate having a plurality of wells spaced apart from each other to form a central space between the plurality of wells; A solution handling method using a solution handling guide device, comprising: a step of attaching the solution handling guide device to the upper portion of the plate; and a step of handling a solution in the first through-hole using the solution handling guide device.

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