WO2023065299A1

WO2023065299A1 - Microscopic sample preparation device and cell phenotype control device

Info

Publication number: WO2023065299A1
Application number: PCT/CN2021/125686
Authority: WO
Inventors: 王雷; 张荣荣; 郦野; 金帆
Original assignee: 深圳先进技术研究院; 中国科学院深圳理工大学(筹)
Priority date: 2021-10-22
Filing date: 2021-10-22
Publication date: 2023-04-27

Abstract

A microscopic sample preparation device and a cell phenotype control device. The microscopic sample preparation device comprises: a forming plate (101) provided with a plurality of forming holes (102) which penetrate through two opposite surfaces of the forming plate (101) and are used for forming a plurality of solid culture media; a sample cell plate (103) provided with a plurality of sample holes (106) which penetrate through two opposite surfaces of the sample cell plate (103) and are used for accommodating a plurality of solid culture media; a cover glass (104) placed on one surface of the sample cell plate (103); and a pressing plate (105) provided with a plurality of pressing columns (107), which are used for pressing the plurality of solid culture media in the plurality of forming holes (102) into the plurality of sample holes (106) and pressing the plurality of solid culture media on the cover glass (104). The plurality of solid culture media can be prepared at a time, and a tableting operation of a plurality of samples can be completed at a time, thereby saving on time, and effectively improving the experiment efficiency, so that misoperation is not prone to occurring, and the cover glass is not easily crushed.

Description

Micro-sample preparation device and cell phenotype control device

technical field

The invention relates to the technical field of micro-experiments, in particular to a micro-sample preparation device and a cell phenotype control device.

Background technique

In the process of biological or medical experiments, in order to better observe individual bacteria or cells on the microscope, the following sample preparation process is often used: drop the bacteria/cell suspension on the cut solid medium (such as agar block); etc. After the agar surface is slightly dry, press the side of the agar block dripping the suspension onto a glass coverslip; then place it on an inverted microscope to observe bacteria or cells. The process described above may be referred to as the tableting process.

The above experimental process requires manual operations such as cutting the agar block, dropping the bacteria/cell suspension on the agar block, pressing the agar block dripped with the suspension on the glass cover slip, etc. The experimenter must operate carefully to get better results. For example, the glass coverslip may be crushed. In addition, when a large number of experimental samples are pressed, it is necessary to operate one by one. The whole experimental process is time-consuming, inefficient, and consumes a lot of time and energy of the experimenter. Operation errors occur, seriously affecting the progress of scientific research or medical diagnosis.

Contents of the invention

In order to solve the problems pointed out by the above-mentioned background technology, an embodiment of the present invention provides a micro sample preparation device and a cell phenotype control device.

According to an aspect of the embodiments of the present invention, there is provided a micro-sample preparation device, comprising: a forming plate having a plurality of forming holes passing through two opposite surfaces of the forming plate for forming a plurality of solid culture media; a well plate having a plurality of sample wells extending across two opposing surfaces of said sample well plate for containing a plurality of said solid media; a cover slip for placement on one surface of said sample well plate; a press plate , a plurality of pressing columns are provided for pressing the plurality of solid culture media in the plurality of shaped holes into the plurality of sample wells and onto the cover glass.

According to another aspect of the embodiments of the present invention, a cell phenotype control device is provided, including a cell culture plate and the micro-sample preparation device of the foregoing embodiments.

The beneficial effects of the embodiments of the present invention at least include:

1. In the embodiment of the present invention, by setting a forming plate with multiple forming holes, a sample pool plate with multiple sample holes, and a pressure plate with multiple pressure columns, it is possible to prepare multiple solid media at one time, and complete multiple solid media at one time. The tablet pressing operation of the sample saves time and effectively improves the efficiency of the experiment. The operation is simple, convenient and fast, and it is not easy to make operation mistakes and crush the cover glass;

2. In the embodiment of the present invention, by setting the first glass sheet, the second glass sheet and the forming plate to form the solid medium together, the surface of the solid medium is guaranteed to be smooth, and a medium with a higher surface quality is provided for the drop suspension;

3. In the embodiment of the present invention, by setting the storage box, the liquid medium can be accommodated, and the forming plate can be well supported when the solid medium is prepared, and the forming plate, the first glass sheet and the second glass sheet can also be supported. Play the role of positioning and alignment;

4. The embodiment of the present invention basically dries the solid medium before dropping the suspension by setting a drying rack, shortens the drying time in the process of dropping the suspension, prevents a large amount of water from being produced in the subsequent tableting process, and then avoids the suspension of the suspension. The microorganisms in the medium swim with the water and fail to meet the experimental requirements;

5. In the embodiment of the present invention, the solid culture medium in the sample pool plate is moisturized by setting a moisturizing member to prevent the solid culture gene from being dehydrated and deformed and separated from the cover glass, which is convenient for the experimenter to perform microscopic observation for a long time;

6. In the embodiment of the present invention, the forming plate and the cell culture plate are detachably connected by setting a connecting plate to form a set of cell phenotype control devices that are easy to disassemble and assemble, and are convenient for optogenetics experiments.

With reference to the following description and accompanying drawings, there are disclosed in detail specific embodiments of the invention, indicating the manner in which the principles of the invention may be employed. It should be understood that embodiments of the invention are not limited thereby in scope. Embodiments of the invention encompass many changes, modifications and equivalents within the spirit and scope of the appended claims.

Description of drawings

The following drawings are only intended to illustrate and explain the present invention schematically, and do not limit the scope of the present invention. in:

The included drawings are used to provide further understanding of the embodiments of the invention, and constitute a part of the specification, are used to illustrate the implementation mode of the invention, and together with the description, explain the principle of the invention. Apparently, the drawings in the following description are only some embodiments of the present invention, and those skilled in the art can obtain other drawings according to these drawings without creative efforts. In the attached picture:

FIG. 1 is a schematic diagram of an example of some components of a microsample preparation device according to an embodiment of the present invention;

2 is a schematic diagram of an example of a forming plate of a microsample preparation device according to an embodiment of the present invention;

3 is a schematic diagram of an example of a sample pool plate of a microsample preparation device according to an embodiment of the present invention;

4 is a schematic diagram of an example of a choke ring of a microsample preparation device according to an embodiment of the present invention;

Fig. 5 is a schematic diagram of an example of a storage box of a microsample preparation device according to an embodiment of the present invention;

6 is a schematic diagram of an example of a sample preparation component of a micro sample preparation device according to an embodiment of the present invention;

7 to 10 are schematic diagrams of the cooperation of components of the microsample preparation device in the sample preparation process according to the embodiment of the present invention;

Figure 11 is a cross-sectional view of the assembly in Figure 10;

Fig. 12 and Fig. 13 are the schematic diagrams of an example of the drying rack of the microsample preparation device of the embodiment of the present invention;

14 to 16 are schematic diagrams of an example of a sample cell plate assembly of a microsample preparation device according to an embodiment of the present invention;

Fig. 17 is a schematic diagram of placing the viscous pad between the sample pool plate and the cover glass of the microsample preparation device according to the embodiment of the present invention;

Fig. 18 is a schematic diagram of an example of a positioning tray of a microsample preparation device according to an embodiment of the present invention;

Fig. 19 and Fig. 20 are schematic diagrams of placing the sample cell plate assembly on the positioning tray of the microsample preparation device according to the embodiment of the present invention;

Fig. 21 and Fig. 22 are schematic diagrams of placing the sample cell plate assembly and the forming plate on the positioning tray of the micro sample preparation device according to the embodiment of the present invention;

Fig. 23 is a schematic diagram of an example of a platen of a microsample preparation device according to an embodiment of the present invention;

Fig. 24 and Fig. 25 are schematic diagrams of the cooperation of the components of the microsample preparation device in the embodiment of the present invention during the tableting process;

Fig. 26 and Fig. 27 are schematic diagrams of the cooperation of components of the microsample preparation device of the embodiment of the present invention after tableting;

Fig. 28 is a schematic diagram of an example of a moisture-retaining member of a microsample preparation device according to an embodiment of the present invention;

Fig. 29 and Fig. 30 are schematic diagrams of cooperation between the moisture-retaining element and the sample pool plate of the microsample preparation device according to the embodiment of the present invention;

Fig. 31 is a schematic diagram of an example of the connecting plate of the micro-sample preparation device according to the embodiment of the present invention;

Fig. 32 and Fig. 33 are schematic diagrams of an example of a cell phenotype control device according to an embodiment of the present invention.

Detailed ways

In order to have a clearer understanding of the technical features, purposes and effects of the present invention, the specific implementation manners of the present invention will now be described with reference to the accompanying drawings. In the description of the present invention, unless otherwise specified, "plurality" means two or more.

The foregoing and other features of the invention will become apparent from the following description, taken with reference to the accompanying drawings. In the specification and drawings, specific embodiments of the present invention are disclosed, which show some embodiments in which the principles of the present invention can be employed. It should be understood that the present invention is not limited to the described embodiments, but rather, This invention includes all modifications, variations and equivalents that come within the scope of the appended claims.

In the embodiments of the present invention, the terms "first", "second", etc. are used to distinguish different elements from the name, but do not indicate the spatial arrangement or time order of these elements, and these elements should not be referred to by these Terminology limited. The term "and/or" includes any and all combinations of one or more of the associated listed items. The terms "comprising", "including", "having" and the like refer to the presence of stated features, elements, elements or components, but do not exclude the presence or addition of one or more other features, elements, elements or components.

In the embodiments of the present invention, the singular forms "a", "the" and the like may include plural forms, which should be broadly understood as "one" or "one type" and not limited to the meaning of "one"; in addition, the term " Said" should be understood as including both singular and plural forms, unless the context clearly indicates otherwise; in addition, the term "according to" should be understood as "based at least in part on...", and the term "based on" should be understood as "based at least in part on... ...", unless the context clearly indicates otherwise; in addition, the term "plurality" means two or more, unless otherwise stated.

In the examples of the present invention, the use of the adjective or adverb modifiers "upper" and "lower", "top" and "bottom", "inner" and "outer", "front" and "back" is only for Relative references between sets of terms are facilitated and do not describe any particular directional limitation on modified terms.

The implementation of the embodiments of the present invention will be described below with reference to the accompanying drawings.

Embodiments of the first aspect

Embodiments of the first aspect of the present invention provide a microscopic sample preparation device.

The microscopic sample preparation device of the embodiment of the present invention includes a sample preparation assembly and a tablet pressing assembly. As shown in FIG. Forming hole 102, a plurality of forming holes 102 are used for forming a plurality of solid medium 200 (as shown in Figure 11), realizes a single preparation of multiple solid medium 200, such as solid medium 200 is an agar block; Figure 14, As shown in FIG. 23 , the pressing assembly includes a sample pool plate 103, a cover glass 104 and a pressing plate 105. The sample pool plate 103 has a plurality of sample holes 106 that run through two opposite surfaces of the sample pool plate 103. The plurality of sample holes 106 can Corresponding to a plurality of forming holes 102 one by one, the cover glass 104 is used to be placed on a surface of the sample cell plate 103, and the pressing plate 105 is provided with a plurality of pressing columns 107, and the plurality of pressing columns 107 can be matched with the plurality of forming holes 102 one by one. Correspondingly, it is used to press a plurality of solid culture media 200 in a plurality of forming holes 102 into a plurality of sample wells 106 and press them on the cover glass 104, for example, a handle 108, handle 108 and pressing column are also provided on the pressing plate 105 107 are respectively arranged on opposite sides of the pressing plate 105 so as to hold the handle 108 to press down the pressing plate 105 .

Sample preparation using the microscopic sample preparation device of this embodiment may include the following steps:

Step S100: Prepare solid medium (such as agar block): as shown in Figure 11, pour the liquid medium (such as agar liquid) into a plurality of forming holes 102 of the forming plate 101, and the liquid medium becomes solid culture after cooling and solidifying Base 200;

Step S200: Dropping: drop the bacteria/cell suspension on the surfaces of multiple solid culture media 200 (called the front side);

Step S300: sheet pressing: as shown in Figure 24 to Figure 27, place the cover glass 104 on the bottom surface of the sample pool plate 103, place the forming plate 101 on the top surface of the sample pool plate 103 (the front side of the solid medium 200 faces Next), the pressing plate 105 is placed on the forming plate 101, at this time, the pressing column 107, the forming hole 102 and the sample hole 106 correspond to each other from top to bottom, and the pressing plate 105 is pressed down until the pressing column 107 covers the plurality of forming holes 102. A plurality of solid culture media 200 are pressed into a plurality of sample wells 106 and pressed on the cover glass 104 to obtain a plurality of microscopic samples in which bacteria/cell suspension droplets are in contact with the cover glass 104, and the samples can be subsequently The pool plate 103 is placed on the microscope platform, and the hanging drop on the solid medium 200 is observed through the cover glass 104 .

The microscopic sample preparation device of this embodiment can realize the preparation of multiple solid culture media at one time, complete the tabletting operation of multiple samples at one time, save time, effectively improve the experimental efficiency, simple and convenient operation, and less prone to operational errors , not easy to crush the coverslip.

Further, the height of the pressing column 107 should not be smaller than the height of the forming hole 102 , so as to press the solid culture medium 200 out of the forming hole 102 and into the sample hole 106 .

Further, the aperture of the sample hole 106 is larger than the aperture of the forming hole 102, so that when the solid medium 200 is pressed into the sample hole 106, the edge of the solid medium 200 is prevented from contacting the hole wall of the sample hole 106 and damaged, and in addition, it is prevented from being damaged. There is trapped gas under the solid medium 200 pressed into the sample hole 106 to cause pressure suppression.

In some embodiments, as shown in Fig. 2, Fig. 3 and Fig. 23, the forming plate 101, the sample pool plate 103 and the pressing plate 105 can all be square plates, and the length dimensions of the forming plate 101, the sample pool plate 103 and the pressing plate 105 can be Same, the width dimension can be the same. A plurality of forming holes 102 on the forming plate 101 can be arranged in multiple rows and columns, such as being arranged in 8 rows and 12 columns, that is, the number of forming holes 102 can be 96, the arrangement and quantity of sample holes 106, the number of pressing columns 107 The arrangement and quantity are consistent with the arrangement and quantity of the forming holes 102, so as to form a one-to-one correspondence.

Further, as shown in FIG. 2 , hole position marks can be set on the two vertical sides of the forming board 101, such as marking with numbers (such as 1 to 12) in the length direction and marking with letters (such as A ~H), in order to describe the position of each forming hole 102, that is, to describe the positions of multiple samples.

Further, as shown in Fig. 3 and Fig. 20, positioning pin installation holes 109 can be respectively provided at two opposite sides of the sample cell plate 103 to fix the positioning pin 144, correspondingly, as shown in Fig. 2, Fig. 20 and Fig. 21 As shown, positioning holes 110 can be respectively provided at the two opposite side plates of the forming plate 101 to be inserted and positioned with the positioning pins 144, so that in the tablet pressing step of step S300, the alignment of the sample cell plate 103 and the forming plate 101 The relative position is positioned so that the two are centered and aligned.

In some embodiments, as shown in FIG. 6 , the sample preparation assembly can also include a first glass slide 111, a choke ring 112 and a second glass slide 113, for example, the thickness of the first glass slide 111 and the second glass slide 113 is less than 0.2mm ultra-thin glass, the first glass sheet 111 is used to be placed on the bottom surface of the forming plate 101 to close the lower end of the forming hole 102, and the choke ring 112 is used to be placed on the top surface of the forming plate 101, that is, the choke ring 112 Around the outside of a plurality of forming holes 102, together with the top surface of the forming plate 101, it forms a pouring groove for pouring liquid culture medium, and the pouring groove communicates with a plurality of forming holes 102; the second glass sheet 113 is used for removing The choke ring 112 is placed on the top surface of the forming plate 101 to form the sample together with the first glass plate and the forming hole 102 to ensure that the surface of the solid medium is smooth and provide a medium with a high surface quality for the drop suspension.

When using the microscopic sample preparation device of this embodiment to prepare samples, in the step of preparing a solid medium in step S100, it may specifically include:

Step S110: as shown in FIG. 7 and FIG. 8, place the first glass sheet 111 on the bottom surface of the forming plate 101, and place the choke ring 112 on the top surface of the forming plate 101;

Step S120: pour the liquid culture medium into the pouring groove inside the choke ring 112 (such as using a large-volume pipette gun), and the liquid culture medium flows into the plurality of forming holes 102 from the pouring groove, wherein the injection amount of the liquid culture medium It is necessary to ensure that after the plurality of forming holes 102 are filled with liquid medium, the liquid level of the liquid medium is still higher than the top surface of the forming plate 101. After pouring is completed, observe whether each forming hole 102 is filled with liquid medium. If it is not full, you can gently shake the forming plate 101 to distribute the liquid medium evenly, ensuring that the multiple forming holes 102 are filled with liquid medium;

Step S130: After the multiple forming holes 102 are filled with liquid culture medium, remove the choke ring 112 from the top surface of the forming plate 101;

Step S140: As shown in Figure 9, slowly put down the second glass sheet 113 attached to one side of the forming plate 101, so that the second glass sheet 113 contacts and infiltrates the liquid culture medium on the top surface of the forming plate 101 to ensure that there is no Bubbles, until the second glass sheet 113 is integrally attached to the top surface of the forming plate 101;

Step S150: As shown in Fig. 10 and Fig. 11 , press down the second glass sheet 113 uniformly and forcefully to squeeze out a layer of liquid culture medium remaining between the second glass sheet 113 and the top surface of the forming plate 101 to form There is as little residual liquid medium as possible between the plate 101 and the second glass sheet 113 to ensure that the two ends of the solid medium 200 formed in each forming hole 102 are smooth;

Step S160: After the liquid culture medium in the forming hole 102 is cooled and solidified, clean up the residual agar on the edge of the forming plate 101, and then place the first glass sheet 111 and the second glass sheet 113 along the bottom surface of the forming plate 101 and the The top surface is translated and pushed away to obtain a cylindrical solid culture medium 200 with flat ends.

Furthermore, the choke ring 112 and the forming plate 101 can be fixed and bonded by magnetic attraction, which is very convenient for disassembly and assembly. For example, specifically, as shown in Figure 4, at least two opposite sides of the choke ring 112 are provided with first magnet installation holes 114 for installing the first magnet; A second magnet installation hole 115 is provided at the two opposite side edges for installing the second magnet. The second magnet corresponds to the first magnet. When the choke ring 112 is placed on the top surface of the forming plate 101, the first magnet and the first magnet Two magnets are magnetically attracted, so that the choke ring 112 and the forming plate 101 are attached and fixed, and the magnet and the magnet mounting hole can be fixed by interference fit.

In order to facilitate the taking and placing of the choke ring 112, side ears (as shown in Fig. 4 and Fig. 8 ) can also be respectively provided at two opposite sides of the choke ring 112, when the choke ring 112 is placed on the top surface of the forming plate 101 At this time, the two side ears are located on the outside of the forming board 101 instead of being attached to the forming board 101 .

Further, the shapes of the first glass sheet 111 , the choke ring 112 and the second glass sheet 113 can all be squares consistent with the shape of the forming plate 101 .

In some embodiments, as shown in FIG. 5 , the microsample preparation device can also include a storage box 116 for supporting and positioning the forming plate 101 when preparing the solid medium 200, and for accommodating the overflow liquid culture medium, the storage box 116 has an open top and is used to place the receiving cavity 117 of the forming board 101, the bottom support frame 118 for supporting the forming board 101, and the outer peripheral limit for the forming board 101. Side limit frame 119, in the example of Fig. 5, bottom support frame 118 and side portion limit frame 119 are all arranged in the storage cavity 117, for example, bottom support frame 118 and side portion limit frame 119 are all ribs, An operation avoidance groove 120 may be provided on the outer peripheral wall of the storage box 116, so as to facilitate putting in components such as the forming board 101 .

When using the microscopic sample preparation device of this embodiment to prepare samples, in step S110, as shown in Figure 6 to Figure 8, the first glass sheet 111, the forming plate 101 and the choke ring 112 can be stacked sequentially from bottom to top On the bottom support frame 118 in the storage cavity 117 , the side limit frame 119 limits the horizontal positions of the first glass sheet 111 , the forming plate 101 and the choke ring 112 , so that the three are centered and aligned. In step S150 , as shown in FIG. 9 , when the second glass sheet 113 is pressed down, the extruded liquid culture medium flows into the storage cavity 117 .

In some embodiments, as shown in FIGS. 14 to 16 , the microsample preparation device may further include a pressure ring 121, which is used to press the cover glass 104 onto the surface of the sample cell plate 103 so that the cover glass The glass slide 104 and the surface of the sample pool plate 103 are closely attached.

When using the microscopic sample preparation device of this embodiment to prepare samples, in the pressing step of step S300, the cover glass 104 can be placed on the bottom surface of the sample cell plate 103, and the pressure ring 121 can be placed on the cover glass 104. The bottom surface is used to fix the cover glass 104 and the sample cell plate 103 through the pressure ring 121 .

In a feasible technical solution, the pressure ring 121 and the sample cell plate 103 are fixed by magnetic attraction. Specifically, the material of the pressure ring 121 is a metal that can be attracted by a magnet, and at least two opposite sides of the sample pool plate 103 are provided with a third magnet mounting hole 122 (as shown in Figure 3 ) for installing a third magnet. , when the pressure ring 121 is placed on the surface of the cover glass 104 facing away from the sample pool plate 103, the third magnet and the pressure ring 121 are magnetically attracted (as shown in Figure 15), so that the cover glass 104 and the sample pool plate 103 Tight fit, easy to disassemble.

Further, as shown in FIG. 3 , two limiting ribs 123 can be set on the surface of the sample pool plate 103 for mounting the cover glass 104 , and the two limiting ribs 123 are respectively arranged on two sides of the sample pool plate 103 . On the opposite side, on the one hand, the cover glass 104 is limited left and right, and on the other hand, the pressure ring 121 is limited left and right.

In some other embodiments, as shown in FIG. 17 , the microsample preparation device can also include a black sticky pad 143, which is used to stick the cover glass 104 on the surface of the sample cell plate 103, and the sticky pad 143 has A plurality of openings run through two opposite surfaces of the adhesive pad 143 , and when the adhesive pad 143 is pasted on the surface of the sample cell plate 103 , the plurality of openings communicate with the plurality of sample wells 106 in one-to-one correspondence.

Compared with the fixing method of the pressure ring in the previous embodiment, the sticky pad 143 is covered with the sample cell plate 103, which can be well attached to the cover glass 104 and the sample cell plate 103 with a smooth surface. The pad 143 is easily separated from the surface of the cover glass 104 and the surface of the sample cell plate 103 after encountering water, and can be pasted repeatedly. The thickness of the sticky pad 143 should be as thin as possible, and the color is black, so as to ensure that no light leaks between the holes when performing optogenetics experiments.

However, the present invention is not limited thereto, and the cover glass 104 and the sample cell plate 103 can also be fixed by other existing connection methods that are easy to disassemble.

In some embodiments, as shown in FIG. 18 , the micro-sample preparation device may further include a positioning tray 124, the positioning tray 124 includes an accommodating cavity 125 with an open top for placing the sample cell plate 103, and a holding chamber for supporting the cover glass. 104 and the central support protrusion 126 of the sample pool plate 103, and the outer limit protrusion 127 for limiting the outer periphery of the cover glass 104 and the sample pool plate 103, when the cover glass 104, the sample pool plate 103 and the When the sample cell assembly composed of the pressure ring 121 is placed on the middle support protrusion 126 (as shown in Figures 19 and 20), the pressure ring 121 is in a suspended state and is located outside the middle support protrusion 126, rather than being connected to the middle support protrusion. 126 fit. The surface of the middle supporting protrusion 126 is a plane, so as to have a good supporting effect on the cover glass 104 .

In the sheet pressing step of step S300, the above-mentioned sample cell assembly can be placed on the middle support protrusion 126 of the positioning tray 124 with the pressure ring 121 facing down (as shown in Figures 18 to 20), and then the forming plate 101 is placed on the top surface of the sample cell plate 103 (as shown in Figure 21 and Figure 22 ) with the front side of the solid medium 200 facing down, at this time, the outer limit protrusion 127 of the positioning tray 124 is opposite to the sample cell assembly and The outer peripheral edge of the forming plate 101 is limited, so that the sample pool plate 103 is aligned with the forming plate 101 to prevent their misalignment. Since the cover glass 104 is supported by the middle support protrusion 126, when the pressing plate 105 is pressed down, the cover glass 104 is not easily deformed and damaged.

In some embodiments, as shown in Figure 12, the microsample preparation device can also include a drying rack 128 for drying the solid medium 200 on the forming plate 101, and the drying rack 128 has at least one left side support block 129 and at least one right side support block 130, the left side support block 129 and the right side support block 130 are arranged at intervals and correspond to each other, and the sides facing each other of the left side support block 129 and the right side support block 130 are respectively provided with a The slot 131 into which the molding board 101 is inserted, makes the molding board 101 air in a suspended state on the drying rack 128, preventing the solid medium 200 in the molding hole 102 from contacting with the drying rack 128 and deforming.

When using the microscopic sample preparation device of this embodiment to prepare samples, in the step of preparing a solid medium in step S100, step S170 may also be included: as shown in Figure 13, the forming plate 101 is placed on the drying rack 128 to Dry the solid medium for 200 g. After the solid medium 200 is basically dried, drop the suspension on the solid medium 200, thereby shortening the drying time in the process of dropping the suspension, preventing a large amount of water from being produced in the subsequent tabletting process, and preventing the microorganisms in the suspension from randomly The water swims away and fails to meet the experimental requirements.

Further, as shown in Fig. 12 and Fig. 13, the drying rack 128 can have a plurality of left side support blocks 129 and a plurality of right side support blocks 130, and a plurality of left side support blocks 129 are spaced apart in the height direction of the drying rack 128 Correspondingly, the plurality of right support blocks 130 are arranged at intervals in the height direction of the drying rack 128 , and correspond one-to-one to the plurality of left support blocks 129 in the horizontal direction.

Further, as shown in Fig. 12 and Fig. 13, the drying rack 128 also includes a lower support plate 132, an upper support plate 133, and a plurality of columns 134 (such as copper columns) connecting the lower support plate 132 and the upper support plate 133, for example The lower support plate 132 and the upper support plate 133 are square hollow frames, and there are four columns 134, which are respectively connected and supported from the four corners of the lower support plate 132 and the upper support plate 133. The left support block 129 and the right side The support block 130 can be fixed on the column 134 .

In some embodiments, as shown in Fig. 28, Fig. 29, and Fig. 30, the micro-sample preparation device can also include a moisture-retaining element 135, the moisture-retaining element 135 includes a moisture-retaining plate 136 and a transparent cover plate 137, and the moisture-retaining plate 136 has a penetrating moisture-retaining plate A plurality of through-holes 138 on two opposite surfaces of 136, a plurality of through-holes 138 are in order to communicate with a plurality of sample holes 106 in one-to-one correspondence, a surface of the moisturizing board 136 is provided with a water storage tank 139, a plurality of through-holes 138 and a storage tank The water tank 139 is connected to allow the water vapor in the water storage tank 139 to enter the through hole 138, and the plurality of through holes 138 and the water storage tank 139 are separated by a flow blocking ring wall 140 to limit the water in the water storage tank 139 from flowing into the through hole 138 The transparent cover 137 can be a glass cover, which is used to cover the surface of the moisturizing board 136 to seal the water storage tank 139 .

During the experiment, when the microscopic sample needs to be observed for a long time, the solid medium 200 in the sample pool plate 103 can be moisturized by using the moisturizing member 135, so as to prevent the solid medium 200 from dehydrating and deforming (such as shrinking to the middle part) and separated from the cover glass 104 .

When using the microscopic sample preparation device of this embodiment to prepare samples, it may also include step S400: as shown in Figure 29 and Figure 30, the lower surface of the moisturizing board 136 facing away from the water storage tank 139 is opposite to the back of the sample pool plate 103 The surface of the cover glass 104 is attached and placed, and now the water storage tank 139 is facing upwards, water is added to the water storage tank 139, and then the transparent cover plate 137 is covered on the upper surface of the moisturizing board 136, so that the water storage tank 139 is closed to obtain an airtight In the moisturizing space, the water in the water storage tank 139 evaporates to maintain a certain humidity in the moisturizing space, effectively preventing the solid medium 200 in the sample pool plate 103 from being dehydrated.

In addition, since the plurality of through holes 138 correspond to the plurality of sample holes 106 one by one, and the transparent cover plate 137 is made of transparent material, it can ensure that the light source above the microscope device is irradiated on the solid medium 200 smoothly, without affecting the normal operation of the optical experiment.

In some embodiments, as shown in FIG. 31 , the micro-sample preparation device further includes an intermediate plate 141. The intermediate plate 141 is provided with a plurality of through holes 142 corresponding to the plurality of forming holes 102. The intermediate plate 141 The forming plate 101 and the cell culture plate 300 of the cell phenotype control device are detachably connected (as shown in FIG. 32 ), so that the microsample preparation device and the cell phenotype control device constitute a set, which is easy to assemble and disassemble. When the forming plate 101 and the cell culture plate 300 are connected by the connecting plate 141, the multiple forming holes 102 on the forming plate 101, the multiple sample holes 106 of the sample pool plate 103, and the multiple through holes 142 on the connecting plate 141 correspond to the multiple microwells 301 on the cell culture plate 300 .

Wherein, the connecting plate 141 and the forming plate 101 may be connected by magnetic attraction, and the connecting plate 141 and the cell culture plate 300 may be connected by an interference fit. For example, specifically, two opposite sides of the connecting plate 141 are provided with magnet installation holes for installing a fourth magnet, and the fourth magnet corresponds to the second magnet of the forming plate 101, so as to connect the connecting plate 141 and the forming plate. The board 101 is magnetically fixed.

Embodiments of the second aspect

The embodiment of the second aspect of the present invention provides a cell phenotype control device, as shown in Figure 32 and Figure 33, the cell phenotype control device includes a cell culture plate 300, a light source control box 400 and Describe the microsample preparation setup. Since in the embodiment of the first aspect, the structure of the microsample preparation device has been described in detail, the content thereof is incorporated here, and the description is omitted here.

In the embodiment of the present invention, for other structures of the cell phenotype control device, reference may be made to related technologies, and descriptions are omitted here.

The present invention has been described above in conjunction with specific embodiments, but those skilled in the art should be clear that these descriptions are all exemplary and not limiting the protection scope of the present invention. Those skilled in the art can make various variations and modifications to the present invention according to the spirit and principle of the present invention, and these variations and modifications are also within the scope of the present invention.

The preferred embodiments of the present invention have been described above with reference to the accompanying drawings. The many features and advantages of these embodiments are apparent from this detailed description, and thus the appended claims are intended to cover all such features and advantages of these embodiments that fall within their true spirit and scope. Moreover, since many modifications and changes will readily occur to those skilled in the art, it is not intended to limit the embodiments of the present invention to the precise structures and operations illustrated and described, but to cover all suitable modifications and equivalents falling within the scope thereof thing.

Claims

A kind of micro sample preparation device, is characterized in that, comprises:

a forming plate having a plurality of forming holes extending through two opposing surfaces of the forming plate for forming a plurality of solid media;

a sample well plate having a plurality of sample wells extending across two opposing surfaces of said sample well plate for containing a plurality of said solid media;

a cover glass for placing on one surface of the sample pool plate;

The pressing plate is provided with a plurality of pressing columns, which are used to press the plurality of solid culture media in the plurality of shaped holes into the plurality of sample holes and press them on the cover glass.
The microsample preparation device according to claim 1, further comprising:

a first glass sheet for placing on the bottom surface of the forming plate;

The choke ring is used to be placed on the top surface of the forming plate, so as to jointly enclose a pouring groove for pouring liquid medium with the top surface of the forming plate, and the pouring groove communicates with a plurality of the forming holes ;

The second glass piece is used to be placed on the top surface of the forming plate after removing the baffle ring, so as to form the solid culture medium together with the first glass plate and the forming hole.
The microsample preparation device according to claim 2, wherein the microsample preparation device further comprises:

The storage box includes a storage cavity with an open top for placing the molding board, a bottom support frame for supporting the molding board, and a side limiting frame for limiting the outer periphery of the molding board .
The microsample preparation device according to claim 1, further comprising:

The pressing ring is used to press the cover glass tightly on the surface of the sample pool plate.
The microsample preparation device according to claim 4, wherein the pressure ring and the sample cell plate are fixed by means of magnetic attraction.
The microsample preparation device according to claim 1, further comprising:

A black adhesive pad for sticking the cover glass on the surface of the sample cell plate, the adhesive pad has a plurality of openings running through the two opposite surfaces of the adhesive pad, a plurality of the openings It is used for one-to-one correspondence with a plurality of the sample holes.
The microsample preparation device according to claim 1, further comprising:

The positioning tray includes an opening at the top and is used to place the accommodating cavity of the sample pool plate, a central support protrusion for supporting the cover glass and the sample pool plate, and a support for the cover glass and the sample pool plate. The outer limit protrusion of the outer peripheral limit of the sample cell plate.
The microsample preparation device according to claim 1, further comprising:

The drying rack has at least one left support block and at least one right support block. The sides of the blocks facing each other are respectively provided with slots for insertion of the profiled plates.
The microsample preparation device according to claim 1, wherein a handle is further provided on the pressing plate, and the handle and the pressing column are respectively arranged on two opposite surfaces of the pressing plate.
The microsample preparation device according to claim 1, further comprising:

The moisturizing board is provided with a plurality of through holes for one-to-one communication with a plurality of the sample holes, a water storage tank is provided on one surface of the moisturizing board, and a plurality of the through holes communicate with the water storage tank, Each of the through holes is separated from the water storage tank by a flow blocking ring wall;

The transparent cover is used to cover the surface of the moisturizing board to close the water storage tank.
The microsample preparation device according to claim 1, further comprising:

The connecting plate is provided with a plurality of through holes for one-to-one correspondence with the forming holes, and the connecting plate is used for detachably connecting the forming plate and the cell culture plate of the cell phenotype control device.
A cell phenotype control device, characterized by comprising the micro sample preparation device and a cell culture plate according to any one of claims 1 to 11.