CN109337814B - Cell well plate - Google Patents
Cell well plate Download PDFInfo
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- CN109337814B CN109337814B CN201811319964.7A CN201811319964A CN109337814B CN 109337814 B CN109337814 B CN 109337814B CN 201811319964 A CN201811319964 A CN 201811319964A CN 109337814 B CN109337814 B CN 109337814B
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- 238000012360 testing method Methods 0.000 claims abstract description 40
- 239000003814 drug Substances 0.000 claims abstract description 33
- 239000007788 liquid Substances 0.000 claims abstract description 24
- 239000011148 porous material Substances 0.000 claims abstract description 15
- 239000011810 insulating material Substances 0.000 claims abstract description 4
- 238000005086 pumping Methods 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
- 238000007789 sealing Methods 0.000 claims description 15
- 239000012780 transparent material Substances 0.000 claims description 6
- 230000007613 environmental effect Effects 0.000 claims description 5
- 230000000149 penetrating effect Effects 0.000 claims 2
- 238000002474 experimental method Methods 0.000 abstract description 11
- 230000008859 change Effects 0.000 abstract description 9
- 230000003993 interaction Effects 0.000 abstract description 4
- 230000002452 interceptive effect Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 70
- 239000003570 air Substances 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 210000004881 tumor cell Anatomy 0.000 description 8
- 238000000034 method Methods 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000007789 gas Substances 0.000 description 4
- 238000005286 illumination Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000004308 accommodation Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- 239000012080 ambient air Substances 0.000 description 2
- 238000009434 installation Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000012774 insulation material Substances 0.000 description 1
- 238000010030 laminating Methods 0.000 description 1
- 239000002135 nanosheet Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/12—Well or multiwell plates
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Clinical Laboratory Science (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention provides a cell pore plate which comprises a plate body and a cover body, wherein the plate body is made of opaque heat-insulating materials, so that a plurality of through holes are opaque and heat-insulating, and each through hole is provided with a transparent plug or a transparent test tube to form an independent and non-interfering space, and the adjacent through holes are not influenced by the change of cells and liquid medicine in the containing space of the transparent plug and the inner wall of the through hole or the transparent test tube, so that the interaction result of the liquid medicine in each through hole and the cells is more authentic. In addition, through transparent plug or transparent test tube accept the mode in the through-hole, after the experiment is accomplished, take out transparent plug or transparent test tube, the cell orifice plate can realize repeatedly usable, only need change transparent plug or transparent test tube and can carry out the experiment next time, and the cost of transparent plug or transparent test tube is for the cell orifice plate, has reduced the experiment cost by a wide margin.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to a cell pore plate.
Background
Cancer tumor treatment is a worldwide difficult problem which is not completely solved at present, researchers find that a two-dimensional material (such as a black phosphorus nano sheet) has good drug loading characteristic and permeability characteristic, and can accurately convey drugs into tumor cells, and then laser or near infrared light irradiation is applied to the two-dimensional material, so that the two-dimensional material is heated to release the drugs, the drugs act on the tumor cells, and the purpose of treating tumor diseases is achieved. In the study of therapeutic methods and therapeutic drugs, different light conditions, different drugs and dosages will have different effects on tumor cells, and therefore, it is necessary to obtain the optimal relationship between light conditions and drugs. In the research process, a large number of repeated experiments are needed, so that the experiment is feasible in vitro, the surrounding environment of tumor cells in vivo is simulated, a large number of target cells (tumor cells and normal cells) and target drugs are needed, interaction is carried out for observation through illumination for a plurality of times, and the experimental process involves cell pore plates for accommodating the target cells and the target drugs.
The present cell plate is a device for accommodating target cells and target drugs in batches, in particular, a plurality of accommodating holes are formed in the cell plate, target cells and target drugs to be acted are placed in each accommodating hole, and a cell culture solution is also arranged in each accommodating hole so as to simulate the real environment in vivo. The cell pore plate can realize the data acquisition work of the proportion of various target cells and target drugs under one-time illumination. In the illumination test process, the accommodating holes are often mutually interfered due to the refraction of light and the difference of temperature. In addition, after a large number of accommodating holes on one cell pore plate are subjected to one test, a part of the plurality of accommodating holes may need to be discarded after being used, so that the cell pore plate cannot be reused, the consumption of the cell pore plate is huge, the cost of the cell pore plate is too high, and the cell pore plate is not environment-friendly.
Disclosure of Invention
The invention aims to provide a cell pore plate which solves the problem of mutual interference among accommodating holes, can be reused and reduces the cost.
In order to achieve the purpose of the invention, the invention provides the following technical scheme:
The utility model provides a cell pore plate, includes plate body and lid, the plate body is opaque thermal-insulated material, be equipped with a plurality of through-holes on the plate body, the lid is located on the plate body, and cover a plurality of through-holes, the lid is in a plurality of through-hole axial direction's projected position is transparent material, a plurality of through-holes are used for holding transparent plug or transparent test tube, transparent plug or transparent test tube with the laminating of through-hole inner wall, transparent plug with the inner wall of through-hole encloses jointly and forms accommodation space, accommodation space or transparent test tube is used for holding cell and liquid medicine.
The plate body comprises a mounting part and a central part, wherein the mounting part surrounds the periphery of the central part, a plurality of through holes are formed in the central part, a sealing groove surrounding the central part is formed in the mounting part, and when the cover body is covered on the plate body, the cover body part stretches into the sealing groove which is used for containing liquid, so that the joint of the cover body and the plate body is filled with the liquid and is sealed.
The mounting portion comprises a first surface and a second surface which are opposite to each other, the central portion comprises a third surface and a fourth surface which are opposite to each other, the first surface and the third surface face the direction of the cover body, the sealing groove is formed in the first surface, the through holes penetrate through the third surface and the fourth surface, the second surface and the fourth surface are coplanar, and in the axial direction of the through holes, the distance between the third surface and the fourth surface is larger than the distance between the first surface and the second surface.
The fourth surface is provided with a first groove and a second groove which are opposite to each other along the inner walls of the through holes, the first groove and the second groove are used for installing a temperature measuring piece, and the temperature measuring piece is used for measuring the temperature inside the through holes.
The installation part further comprises a first side face and a second side face which are opposite to each other, the first side face and the second side face are connected with the first surface and the second surface, the first side face and the second side face are located on two sides of the central part respectively, a plurality of third connecting holes are formed in the first side face, a plurality of fourth connecting holes are formed in the second side face, the first connecting holes, the second connecting holes, the third connecting holes and the fourth connecting holes are all used for being connected with a connecting rod, and the connecting rod is used for driving the plate body to move.
The first connecting hole extends from the first surface to the second surface, the first connecting hole is not penetrated through the second surface, a first sub hole and a second sub hole which are arranged along the first direction and are opposite to each other are arranged on the periphery of the first connecting hole, a third sub hole is arranged at the bottom wall of the first connecting hole, the radius of the third sub hole is not smaller than the distance from the first sub hole to the center of the first connecting hole, a fourth sub hole and a fifth sub hole are further arranged on the plate body on one side, close to the first surface, of the third sub hole, the fourth sub hole and the fifth sub hole are arranged on the periphery of the first connecting hole, the fourth sub hole and the fifth sub hole are communicated with the first connecting hole and the third sub hole, the fourth sub hole and the fifth sub hole are arranged oppositely and are not penetrated through the first surface, the third sub hole and the fifth sub hole are arranged along the second direction, and the first direction and the second direction are not parallel.
The cover body comprises a top plate and a side plate, the side plate is connected around the top plate, the side plate is used for extending into the sealing groove, the axial projections of the through holes are formed in the top plate, the top plate comprises a fifth surface and a sixth surface which are opposite, the sixth surface faces the plate body, a plurality of concave lenses are arranged on the fifth surface, a plurality of convex lenses are arranged on the sixth surface, each concave lens and each convex lens correspond to each through hole on the plate body, and the concave lenses and the convex lenses are matched to enable the sectional area of a light beam emitted from the fifth surface to be enlarged on the sixth surface, so that the light beam emitted into the through hole covers a larger area.
The sixth surface is further provided with a plurality of steam absorbing members, each steam absorbing member corresponds to one convex lens, each steam absorbing member comprises a micro-channel, an inlet of each micro-channel is close to a mirror surface of the convex lens, and an outlet of each micro-channel is communicated with a water pumping hole formed in the side plate.
The side plates are provided with water pumping holes and air inlets, the water pumping holes are used for being connected with water pumping equipment, the water pumping equipment is used for pumping out water vapor in the space between the cover body and the plate body, the air inlets are used for being connected with air inlet equipment, the air inlet equipment is used for providing environmental gas in the space between the cover body and the plate body, and the environmental gas is used for providing experimental environment for the cells.
The side plate around the water pumping hole is provided with a hole shielding structure, the hole shielding structure is used for shielding the water pumping hole, the hole shielding structure comprises a supporting rod, an operating rod, a pressing plate, a sliding plate and a sliding rod, one end of the supporting rod is fixed on the side plate, the operating rod is elastically rotated and connected to the supporting rod, the pressing plate comprises a first flat plate and a second flat plate, the first flat plate and the extending direction of the second flat plate form an included angle, the first flat plate is fixedly connected with the operating rod, the second end, opposite to the first end, of the first flat plate is connected with the second flat plate, the operating rod is elastically abutted to the supporting rod, so that the second flat plate is attached to the side plate, a mounting groove is formed in the pressing plate, the sliding plate is contained in the mounting groove and covers the water pumping hole, the pressing plate is pressed by the pressing plate and attached to the side plate, the sliding groove is formed in the top plate, the sliding rod is contained in the sliding groove and is connected with the sliding plate in the sliding groove, the sliding rod is connected with the sliding plate through the sliding rope in a sliding mode, and the sliding rope is exposed out of the sliding plate.
The plate body is made of opaque heat-insulating materials, light-tight and heat-insulating are arranged between the through holes, so that independent and noninterference spaces are formed after each through hole accommodates the transparent plug or the transparent test tube, and adjacent through holes cannot be affected by changes of cells and liquid medicine in the accommodating space of the transparent plug and the inner wall of the through hole or the transparent test tube, so that the interaction result of the liquid medicine in each through hole and the cells is more true and reliable. In addition, through transparent plug or transparent test tube accept the mode in the through-hole, after the experiment is accomplished, take out transparent plug or transparent test tube, the cell orifice plate can realize repeatedly usable, only need change transparent plug or transparent test tube and can carry out the experiment next time, and the cost of transparent plug or transparent test tube is for the cell orifice plate, has reduced the experiment cost by a wide margin.
Drawings
In order to more clearly illustrate the embodiments of the invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1a is a schematic exploded perspective view of a cell well plate according to one embodiment of the present invention;
FIG. 1b is a schematic perspective view of the plate body of the cell well plate of FIG. 1;
FIG. 1c is a schematic perspective view of a cover of the cell well plate of FIG. 1;
FIG. 1d is a schematic top view of the cell well plate of FIG. 1;
FIG. 2a is a schematic perspective view of a plate body according to an embodiment;
FIG. 2b is a schematic view of the partial enlarged structure at A in FIG. 2 a;
FIG. 3a is a schematic plan view of a plate body of an embodiment;
FIG. 3b is a schematic bottom plan view of the plate of FIG. 3 a;
FIG. 3c is a schematic view of a partial enlarged structure at B in the plate body of FIG. 3 a;
FIG. 3d is a schematic cross-sectional view of the structure of FIG. 3c taken along the direction E-E;
FIG. 3e is a schematic cross-sectional view taken along the direction F-F in FIG. 3 c;
FIG. 3f is a schematic illustration of the structure of a connecting rod of an embodiment;
FIG. 3g is a schematic top view of the connecting rod of FIG. 3 f;
FIG. 4a is a schematic exploded view of a cross-sectional structure of a cell well plate of one embodiment;
FIG. 4b is a schematic view of the partial enlarged structure at C in FIG. 4 a;
FIG. 4c is a schematic diagram of the use of one embodiment of FIG. 4 b;
FIG. 4d is a schematic diagram of the use of the alternative embodiment of FIG. 4 b;
FIG. 5a is a schematic cross-sectional view of a cell well plate of an embodiment;
FIG. 5b is a schematic view of the partial enlarged structure at D in FIG. 5 a;
FIG. 5c is a schematic diagram of the use of one embodiment of FIG. 5 b;
FIG. 5d is a schematic cross-sectional area structure of a beam covered by a via of an embodiment;
FIG. 5e is a schematic cross-sectional area structure of a beam covered by a via in another embodiment;
FIG. 6a is a schematic perspective view of a cover of an embodiment;
FIG. 6b is a schematic top view of the cover of FIG. 6 a;
FIG. 6c is a schematic cross-sectional view of the structure of FIG. 6b taken along the M-M direction;
FIG. 6d is a schematic bottom view of the cover of FIG. 6 a;
FIG. 6e is a schematic view of a portion of a hole blocking structure according to one embodiment;
FIG. 6f is a schematic view of a partially enlarged structure of the cover of FIG. 6 a;
fig. 6g is a schematic perspective view of the cover of fig. 6a in an initial state.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Referring to fig. 1 and 2, an embodiment of the invention provides a cell pore plate, which includes a plate body 10 and a cover body 20, wherein the plate body 10 is made of opaque heat insulation material, a plurality of through holes 13 are formed in the plate body 10, the cover body 20 is covered on the plate body 10 and covers the plurality of through holes 13, and projection positions of the cover body 20 on the axial directions of the plurality of through holes 13 are made of transparent material. Referring to fig. 4c and fig. 4d, the through holes 13 are used for accommodating the transparent plugs 30 or the transparent test tubes, the transparent plugs 30 or the transparent test tubes are attached to the inner walls of the through holes 13, the transparent plugs 30 and the inner walls of the through holes 13 together enclose to form an accommodating space, and the accommodating space or the transparent test tubes are used for accommodating cells and the liquid medicine 40.
According to the invention, the plate body 10 is made of opaque heat-insulating materials, so that a plurality of through holes 13 are opaque and heat-insulating, and each through hole 13 is provided with the transparent plug 30 or the transparent test tube to form an independent and non-interfering space, and the adjacent through holes 13 are not influenced by the change of cells and liquid medicine 40 in the accommodating space between the transparent plug 30 and the inner wall of the through hole 13 or in the transparent test tube, so that the interaction result of the liquid medicine in each through hole 13 and the cells is more authentic. In addition, through transparent plug 30 or transparent test tube accept the mode in through-hole 13, after the experiment is accomplished, take out transparent plug 30 or transparent test tube, the cell orifice plate can realize repeatedly usable, only need change transparent plug 30 or transparent test tube can carry out the experiment next time, and the cost of transparent plug 30 or transparent test tube is compared with the cell orifice plate, has reduced the experiment cost by a wide margin.
The through hole 13 in this embodiment is a circular hole, and the extending direction of the axis of the through hole 13 is perpendicular to the plane of the whole cell plate. Referring to fig. 5c, when light is applied to the cell plate, light is irradiated from the outside of the cover 20 to the plate 10, and the direction of the light is parallel to the axis of the through hole 13. Since light enters from one end of the through hole 13 and exits from the other end, the transparent plug 30 or the transparent test tube is made of transparent material, and has light transmittance, and light is detected at the light exit position, and light irradiation condition data can be obtained by comparing the change of the light and the light.
The plurality of through holes 13 in the present embodiment are arranged at intervals on the cell plate, preferably in an array, and the number of through holes 13 may be 48, 72, 96, etc., and the arrangement of the through holes 13 on the cell plate may be 6 rows×8 columns, 8 rows×9 columns, 8 rows×12 columns, etc., although the arrangement is not limited thereto, and other numbers and arrangements of through holes 13 are also possible. Obviously, the specific size of the through hole 13 is not limited in this embodiment either.
The cells of this embodiment are target cells, i.e., tumor cells or normal cells, the liquid medicine is a drug for treating tumor diseases, and the culture solution is a liquid simulating an in vivo environment, and specific components thereof are not limited herein. In this embodiment, by respectively accommodating normal cells and tumor cells in different through holes 13, the data of the effect of light and medicine on the normal cells and the effect on the tumor cells can be obtained simultaneously, so that the light conditions and the components of the medicine can be analyzed later to obtain the optimal light conditions and the components of the medicine.
In an embodiment, referring to fig. 3a and fig. 4a, the plate body 10 includes a mounting portion 11 and a central portion 12, the mounting portion 11 surrounds the periphery of the central portion 12, the plurality of through holes 13 are formed in the central portion 12, a sealing groove 106 surrounding the central portion 12 is formed in the mounting portion 11, when the cover body 20 is covered on the plate body 10, a portion of the cover body 20 extends into the sealing groove 106, and the sealing groove 106 is used for accommodating liquid, so that a joint between the cover body 20 and the plate body 10 is filled with the liquid and sealed.
In this embodiment, the liquid contained in the seal groove 106 is water, and after the cover 20 extends into the seal groove 106, the gap between the cover 20 and the plate 10 is filled with water, so that the central portion 12 and the cover 20 enclose to form a closed space, the external space and the through hole 13 are not communicated, so that the cells and the liquid medicine 40 are in a stable environment, and the influence of other factors on experimental results is reduced.
In an embodiment, referring to fig. 1d and fig. 3a, the central portion 12 is rectangular and includes three right angles and a rounded corner, the position of the sealing groove 106 corresponding to the rounded corner is set to be arc-shaped, and the cover 20 is set to be a shape 205 corresponding to the arc-shaped sealing groove 106, so that the cover 20 and the plate 10 have a preset cover position, and alignment of the cover 20 and the plurality of through holes 13 is facilitated.
Referring to fig. 4a, the mounting portion 11 includes a first surface 111 and a second surface 112 opposite to each other, the central portion 12 includes a third surface 121 and a fourth surface opposite to each other, and the second surface 112 is coplanar with the fourth surface, so the second surface and the fourth surface are denoted by the reference numerals of the second surface 112. The first surface 111 and the third surface 121 face the direction of the cover 20, and the sealing groove 106 is formed on the first surface 111. The plurality of through holes 13 penetrate the third surface 121 and the fourth surface 112, and a distance between the third surface 121 and the fourth surface 112 is greater than a distance between the first surface 111 and the second surface 112 in an axial direction of the through holes 13. In other words, the central portion 12 is larger than the thickness dimension of the mounting portion 11, since the second surface is coplanar with the fourth surface, i.e., the central portion 12 is higher than the height dimension of the mounting portion 11.
In this embodiment, the first surface 111, the second surface 112, the third surface 121 and the fourth surface are all planar, and the axis of the through hole 13 is perpendicular to the third surface 121 and the fourth surface 112. The central portion 12 is provided to be higher than the mounting portion 11 in height dimension so that the axial extension length of the through hole 13 is sufficiently long, the transparent plug 30 or the transparent test tube can be accommodated in the through hole 13, and also has a sufficient accommodation space to accommodate cells and the drug solution 40.
Referring to fig. 2a, 2b and 4a to 4d, first and second grooves 131 and 132 are formed on the fourth surface 112 along the inner walls of the plurality of through holes 13, the first and second grooves 131 and 132 being used for mounting a temperature measuring member 50 for measuring the temperature inside the plurality of through holes 13.
In this embodiment, the temperature measuring device 50 is partially accommodated in the first groove 131 and the second groove 132, and when the transparent plug 30 or the transparent tube needs to be replaced, the temperature measuring device 50 can be detached, and the transparent plug 30 or the transparent tube is ejected from one end of the fourth surface 112 toward the third surface 121, so that the connection between the temperature measuring device 50 and the inner wall of the first groove 131 and the inner wall of the second groove 132 is detachable. The temperature measuring member 50 may be a temperature sensor, but may be other temperature measuring devices.
Since the light of the through hole 13 needs to be measured from one end of the fourth surface 112, in one embodiment, the temperature measuring element 50 is made of a transparent material, the light can be transmitted, and a light measuring device is additionally disposed on the side of the temperature measuring element 50 away from the cover 20, and after the temperature measuring element 50 measures the temperature and the light, the temperature and the light data are transmitted to a data processing device (not shown in the figure), so that the data can be analyzed and processed. In another embodiment, the temperature measuring element 50 also has the function of measuring light, and the light is received by the temperature measuring element 50 to obtain data of the light, and the data of the temperature can be transmitted to a data processing device (not shown in the figure) together, so that the data can be analyzed and processed.
The temperature measuring member 50 may be attached to the transparent plug 30, i.e. the temperature measuring member 50 is attached to a surface of the transparent plug 30 remote from the first surface 111. Or the temperature measuring part 50 is attached to the transparent test tube, please refer to fig. 4d specifically, the transparent test tube includes a flange 321, a side wall 322 and a bottom wall 323, the side wall 322 is connected to the periphery of the bottom wall 323 and attached to the inner wall of the through hole 13, the bottom wall 323 is in a flat plate shape, one side of the bottom wall 323 is attached to the temperature measuring part 50, the flange 321 is disposed at an end portion of the side wall 322 far away from the bottom wall 323 and protrudes in a direction far away from the inner cavity 33 of the transparent test tube, and the flange 321 surrounds the periphery of the side wall 322 and is used for being hung on the third surface 121 of the central portion 12. The internal cavity 33 of the transparent tube is used to contain cells and a liquid medicine 40.
Referring to fig. 4a, and referring to fig. 1a, fig. 1b, fig. 3a, and fig. 3b, the first surface 111 is provided with a plurality of first connection holes 101, the second surface 112 is provided with a plurality of second connection holes 102, the mounting portion 11 further includes a first side 113 and a second side 114 opposite to each other, the first side 113 and the second side 114 are connected to the first surface 111 and the second surface 112, the first side 113 and the second side 114 are respectively located at two sides of the central portion 12, the first side 113 is provided with a plurality of third connection holes 103, and the second side 114 is provided with a plurality of fourth connection holes 104. Referring to fig. 3f and 3g, the first connecting hole 101, the second connecting hole 102, the third connecting hole 103 and the fourth connecting hole 104 are all used for connecting with the connecting rod 60, and the connecting rod 40 is used for driving the plate body 10 to move.
In this embodiment, in the test process, the cell plate is required to be moved, for example, the cell plate is moved to another position, or the cell plate is lifted up integrally to perform a shaking operation, so as to achieve sufficient contact between the cells and the liquid medicine 40, and the cell plate is required to be moved in a three-dimensional space, i.e., the movement of the cell plate includes up-and-down movement, front-and-back movement, left-and-right movement, and swinging operation. Therefore, the first connecting hole 101, the second connecting hole 102, the third connecting hole 103 and the fourth connecting hole 104 are all connected with the connecting rod 60, and the connecting rod 40 drives the plate body 10 to move, so that the cell pore plate is controlled to move by a mechanical structure, the operation is not needed, and the labor intensity can be reduced. It will be appreciated that the connection between the connection rod 60 and the first connection hole 101, the second connection hole 102, the third connection hole 103 and the fourth connection hole 104 is a detachable connection, so that the connection rod 60 can be easily removed to place the cell well plate on a table top or replace the cell well plate. Wherein, the cell plate moves along with the movement of the connecting rod 60, one end of the connecting rod 60 is connected with the connecting hole, and the other end is connected with a driving device (not shown in the figure), and the driving device drives the connecting rod 60 to move so as to drive the cell plate to move.
On the first surface 111, a plurality of first connection holes 101 are provided on the outer periphery of the seal groove 106, and preferably, the mounting portion 11 is rectangular overall, and 4 first connection holes 101 are provided at four corners of the mounting portion 11. Similarly, the plurality of second connection holes 102 provided on the second surface 112 are also 4 and provided at the four corners of the mounting portion 11. On the third surface 113, the number of the plurality of third connection holes 103 provided is 2 or more, and the intervals between the plurality of third connection holes 103 are as far as possible. The fourth plurality of connecting holes 104 on the fourth surface 114 are similar to the third connecting holes 103, and will not be described again.
The mounting portion 11 further includes a third side and a fourth side, where the third side and the fourth side are connected to the first side 113 and the second side 114, and a plurality of connection holes may be formed in the third side and the fourth side, which are not described herein. Through the above arrangement, a plurality of connecting holes are formed in the mounting portion 11 in the front, rear, left and right directions, and the cell orifice plate is moved after being connected with the connecting rod 60.
In an embodiment, referring to fig. 3a and fig. 3c to fig. 3g, the first connecting hole 101 extends from the first surface 111 toward the second surface 112, and does not penetrate the second surface 112, a first sub-hole 1011 and a second sub-hole 1012 are disposed on the outer periphery of the first connecting hole 101, which are opposite to each other in the first direction, a third sub-hole 1014 is disposed at the bottom wall of the first connecting hole 101, the radius of the third sub-hole 1014 is not smaller than the distance from the first sub-hole 1011 to the center of the first connecting hole 101, a fourth sub-hole 1015 and a fifth sub-hole 1016 are further disposed on the plate body 10 on one side of the third sub-hole 1014 near the first surface 111, the fourth sub-hole 1015 and the fifth sub-hole 1016 are disposed on the outer periphery of the first connecting hole 101, the fourth sub-hole 1015 and the fifth sub-hole 1016 are in communication with the first connecting hole 101 and the third sub-hole 1014, and the fourth sub-hole 1015 and the fifth sub-hole 1016 are disposed on the outer periphery of the first connecting hole 101, which is not parallel to the first surface 1016, and the fourth sub-hole 1015 and the fifth sub-hole 1016 are disposed in the second direction.
The connecting rod 60 has a first bump 61 and a second bump 62 at one end, and the first bump 61 and the second bump 62 are disposed on two opposite sides of the end surface of the connecting rod 60 in the radial direction. When connecting the connecting rod 60 with the first connecting hole 101, one end of the connecting rod 60 provided with the first bump 61 and the second bump 62 is aligned with the first connecting hole 101, specifically, the first bump 61 is aligned with the first sub-hole 1011, the second bump 62 is aligned with the second sub-hole 1012, the connecting rod 60 is inserted into the first connecting hole 101 so that the first bump 61 and the second bump 62 are inserted into the third sub-hole 1014, the connecting rod 60 is rotated so that the first bump 61 and the second bump 62 are rotated in the space of the third sub-hole 1014 until the first bump 61 is aligned with the fourth sub-hole 1015, the second bump 62 is aligned with the fifth sub-hole 1016, and the connecting rod 60 is pulled against the cell-orifice plate so that the first bump 61 is inserted into the fourth sub-hole 1015, and the second bump 62 is inserted into the fifth sub-hole 1016, thereby completing the installation of the connecting rod 60. When the connecting rod 60 needs to be removed, the above steps are reversed.
In order to facilitate the connecting rod 60 extending into the first connecting hole 101, a transition fillet 1013 is disposed at the wall surfaces of the first connecting hole 101 and the first and second sub-holes 1011 and 1012 and the first surface 111, and the transition fillet 1013 can enable the connecting rod 60 to be aligned with the first connecting hole 101 rapidly, so that the connecting rod 60 can be installed more rapidly.
The second, third, fourth, fifth and sixth connection holes 102, 103, 104, and 101 may have the same structure as the first connection hole 101, so that the same connection rod 60 may be used to connect with each of the connection holes.
Referring to fig. 1a, 1b and 5a to 5e, the cover 20 includes a top plate 22 and a side plate 21, the side plate 21 is circumferentially connected around the top plate 22, the side plate 21 is configured to extend into the seal groove 106, the axial projections of the plurality of through holes 13 are projected on the top plate 22, the top plate 22 includes a fifth surface 221 and a sixth surface 222 opposite to each other, the sixth surface 222 faces the plate 10, the fifth surface 221 is provided with a plurality of concave lenses 23, the sixth surface 222 is provided with a plurality of convex lenses 24, each of the concave lenses 23 and each of the convex lenses 24 corresponds to each of the through holes 13 on the plate 10, and the concave lenses 23 and the convex lenses 24 are configured to expand the cross-sectional area of the light beam incident from the fifth surface 221 on the sixth surface 222, so that the light beam incident into the through holes 13 covers a larger area.
Referring to fig. 5c, a plurality of arrows arranged in parallel are used to represent the light beam, and referring to fig. 5d, when the concave lens 23 and the convex lens 24 are not provided, the first cross-sectional area 01 of the light beam after entering the through hole 13 is smaller. Referring to fig. 5e, when the concave lens 23 and the convex lens 24 are disposed, the second cross-sectional area 02 of the light beam after entering the through hole 13 is significantly larger than the first cross-sectional area 01. Because the cross-sectional area of the light beam provided by the light source is often small and is far smaller than the diameter of the through hole 13 due to the limitation of the light source of the laser or near infrared light, only a partial area can be covered when the light beam irradiates into the accommodating space or the transparent test tube in the through hole 13. During the test, it was found that the part of the cells irradiated by the beam was essentially dead, but the areas not irradiated by the beam were mostly living, the more far from the beam. It is necessary to increase the cross-sectional area of the light beam incident into the through hole 13 to verify whether or not the illumination intensity causes excessive cell death rather than the drug property. Therefore, the beam is expanded by a concave lens 23, and then collimated by a convex lens 24, so as to expand the cross-sectional area of the beam.
Referring to fig. 5a and fig. 5b, in combination with fig. 1, in one embodiment, a plurality of vapor absorbing members are further disposed on the sixth surface 222, each vapor absorbing member corresponds to one of the convex lenses 24, the vapor absorbing members include a micro-channel 255, an inlet of the micro-channel 255 is close to a mirror surface of the convex lens 24, and an outlet of the micro-channel 255 is communicated with a water pumping hole 201 disposed on the side plate 21.
Because the human body environment needs to be simulated in the test process, the temperature of the environment where the cells and the liquid medicine 40 are located is almost equal to the human body temperature, namely, the temperature of the environment where the cells and the liquid medicine 40 are located is not lower than 36 ℃, so that the vapor evaporated from the cells and the liquid medicine 40 is attached to the convex lens 24 to influence the light irradiation into the through hole 13, the vapor needs to be removed, and the water pumping hole 201 is arranged to suck the vapor. The micro-channel 255 is arranged close to the convex lens 24, and according to the fluid mechanics theory, the smaller the flow channel is, the larger the flow velocity is, so that the micro-channel 255 can suck the water vapor on the mirror surface of the convex lens 24 more quickly.
Specifically, the vapor absorbing member includes an upper plate 251, a lower plate 252 and a transverse plate 253, wherein the upper plate 251 is connected to the sixth surface 222, and is in a cover shape as a whole, i.e. one end of the upper plate 251 is connected to the edge position of the convex lens 24 on the sixth surface 222, and the opposite end is spread outwards. In other words, the upper plate 251 has a truncated cone shape as a whole, and one end connected to the sixth surface 222 surrounds the outer periphery of the convex lens 24, and the other end spreads in a direction away from the convex lens 24. The lower plate 252 is similar to the upper plate 251 in shape and also has a truncated cone shape, the lower plate 252 is positioned on the inner side of the upper plate 251, one end of the lower plate 252 is close to the mirror surface of the convex lens 24, but a gap is formed between the lower plate 252 and the convex lens 24, and the micro-channel 255 formed between the lower plate 252 and the upper plate 251 has a cone shape. The transverse plate 253 is connected to one end of the lower plate 252 far away from the convex lens 24, and the transverse plate 253 is made of transparent material, so that light irradiation into the through hole 13 is not affected. The lower plate 252 and the transverse plate 253 are integrally connected to the upper plate 251 through a plurality of connection ribs (not shown) provided in the micro-channels 255, thereby achieving fixation of the vapor absorbing member. A connecting pipe may be provided between the outlet of the micro channel 255 and the pumping hole 201, thereby achieving connection therebetween.
Referring to fig. 4a in combination with fig. 1a and 1c, the side plate 21 is provided with the water pumping hole 201 and the air inlet 202, and the water pumping hole 201 is used for connecting with a water pumping device (not shown in the figure) for pumping out the water vapor in the space between the cover 20 and the plate 10, more specifically, the water vapor attached to the top plate 22, such as the convex lens 24. The air intake 202 is adapted to be connected to an air intake device (not shown) for providing an ambient air in the space between the cover 20 and the plate 10, which ambient air is adapted to provide an experimental environment for the cells.
In the test, it is often necessary to change the environment to test the change condition of the cells in different environments, for example, different gases are input, so that the cells are observed to change in different gas environments, for example, whether substances are generated in the cells, the death condition of the cells, etc., so as to obtain a preferable environment which is possibly beneficial to treating tumor diseases, and therefore, the air inlet holes 202 are arranged on the side plate 21 of the cover body 20. Alternatively, a plurality of water pumping holes 201 and air intake holes 202 may be provided, as shown in fig. 1a and 1c, the number of water pumping holes 201 is 1, the number of air intake holes is 3, and the number of air intake holes 202, 203 and 204 are respectively.
Referring to fig. 6a to 6g, on the top plate 22 of the cover plate 20, a plurality of concave lenses 23 and convex lenses 24 are arranged in an array, and the concave lenses 23 and the convex lenses 24 may be integrally formed with the cover plate 20, or of course, the concave lenses 23 and the convex lenses 24 may be mounted on the cover plate 20. The sixth surface 222 of the top plate 22 around the convex lenses 24 is provided with steam pipelines 241 connected in series or parallel, and a plurality of steam absorbing members arranged around the convex lenses 24 are communicated with the steam pipelines 241. The steam pipe 241 is connected with the corresponding steam sucking parts of the convex lenses 24 and then is converged to the steam pipe joint 242, and the steam pipe joint 242 extends to the water pumping hole 201 so as to be connected with the pipe joint of external water pumping equipment. The steam pipe joint 242 can be multiple, so that the sucking efficiency of the steam on the convex lens 24 can be accelerated. In another embodiment, there are 2 steam pipe connectors 242, one of which is used for sucking the steam on the convex lens 24, and the other steam pipe connector 242 can be connected with an external air inlet device to provide the environmental air in the space between the cover 20 and the plate 10.
In one embodiment, referring to fig. 6a to 6g, a hole shielding structure is disposed on the side plate 21 around the pumping hole 201, and the hole shielding structure is used for shielding the pumping hole 201. The hole shielding structure includes a support bar 71, an operation bar 72, a pressing plate 73, a sliding plate 74, and a sliding bar 75. One end of the supporting rod 71 is fixed on the side plate 21, and the operating rod 72 is elastically rotatably connected to the supporting rod 71. The pressing plate 73 comprises a first flat plate 731 and a second flat plate 732, wherein an included angle is formed between the first flat plate 731 and the extending direction of the second flat plate 732, a first end of the first flat plate 731 is fixedly connected with the operating rod 72, and a second end of the first flat plate 731 opposite to the first end is connected with the second flat plate 732.
In the initial state, the operation rod 72 and the support rod 71 elastically abut against each other, so that the second plate 732 is attached to the side plate 21. The pressure plate 73 is provided with a mounting groove 733, the sliding plate 74 is accommodated in the mounting groove 733 and covers the pumping hole 201, and is pressed by the pressure plate 73 to be attached to the side plate 21, the top plate 22 is provided with a sliding groove 76, the sliding rod 75 is accommodated in the sliding groove 76 and slides in the space of the sliding groove 76, and a connecting rope (not shown in the figure) is connected between the sliding rod 75 and the sliding plate 74.
In the use state, the operation lever 72 rotates to drive the first flat plate 731 and the second flat plate 732 to move, so that the second flat plate 732 is gradually far away from the side plate 21, and simultaneously slides the sliding lever 75 to drive the sliding plate 74 to move to expose the pumping hole 201, so that the pumping hole 201 can be connected with a pumping device.
When the use is stopped, the steps are reversed, so that the water pumping hole 201 can be covered, and dust and the like can be prevented from entering the space between the cover body 20 and the plate body 10 to cause pollution.
The included angle between the first flat plate 731 and the second flat plate 732 is in a range of 90 ° to 150 °, preferably 135 ° to 150 °, so that when the second flat plate 732 is attached to the side plate 21, the first flat plate 731 protrudes out of the side plate 21, and when the operating lever 72 rotates, the first flat plate 731 can be driven to follow movement without interference. Specifically, the middle part of the operating rod 72 is pivoted with the supporting rod 71, so that the operating rod 72 can rotate relative to the supporting rod 71, an elastic structure can be arranged at the pivot position of the pivoting, so that the operating rod 72 is elastically supported, and an elastic structure can also be arranged on the side plate 21 to support at the position where the operating rod 72 is far away from the pivoting, and the elastic structure can be a spring, such as a torsion spring, a compression spring and the like.
The shape of the mounting groove 733 formed on the pressing plate 73 corresponds to the shape of the sliding plate 74, and the mounting groove 733 penetrates through one side edge of the second flat plate 732 away from the first flat plate 731, so that the second flat plate 732 forms two strip-shaped plates extending from the first flat plate 731. The mounting groove 733 may also open to a partial region of the first panel 731. The shape of the sliding plate 74 is preferably the same as the pumping hole 201, and if the pumping hole 201 is a circular hole, the shape of the sliding plate 74 is in a pie shape. In the initial state, the slide plate 74 is limited in the space of the mounting groove 733, and when the water suction hole 201 is required to be used, the slide plate 74 slides on the side plate 21 in the vertical direction, so that the extending direction of the mounting groove 733 is also the vertical direction. In order to facilitate connection with the slide lever 75 through the connection rope, the slide plate 74 is provided to include a main body portion 741 and a protrusion portion 742, the protrusion portion 742 is provided at an edge position of the main body portion 741, and a rope connection hole 743 is provided on the protrusion portion 742, and the connection rope passes through the rope connection hole 743 to connect the slide plate 74, so that the slide plate 74 can be driven to move.
The extending direction of the sliding groove 76 and the sliding direction of the sliding plate 74 are in the same plane, the sliding groove 76 penetrates through the top plate 22 to the surface of the side plate 21, and the connection part of the bottom wall of the sliding groove 76 and the surface of the side plate 21 adopts a rounded corner transition, so that the friction force of the connecting rope is reduced. At least two fixing positions are provided when the slide bar 75 slides in the slide groove 76, that is, when the slide plate 74 covers the water pumping hole 201, the slide bar 75 is fixed, and when the slide plate 74 slides to expose the water pumping hole 201, the slide bar 75 is fixed. Regardless of the position of the slide plate 74, the connecting cord is always in a tight state, making the overall structure of the cover 20 compact.
The above-mentioned hole shielding structure of the water pumping hole 201 is also suitable for shielding the air inlet hole, and may be referred to in other embodiments, and will not be described again.
The above disclosure is only a preferred embodiment of the present invention, and it should be understood that the scope of the invention is not limited thereto, and those skilled in the art will appreciate that all or part of the procedures described above can be performed according to the equivalent changes of the claims, and still fall within the scope of the present invention.
Claims (6)
1. The cell pore plate is characterized by comprising a plate body and a cover body, wherein the plate body is made of opaque heat-insulating materials, a plurality of through holes are formed in the plate body, the cover body is covered on the plate body and covers the through holes, the projection position of the cover body on the axial direction of the through holes is made of transparent materials, the through holes are used for accommodating transparent plugs or transparent test tubes, the transparent plugs or the transparent test tubes are attached to the inner walls of the through holes, the transparent plugs and the inner walls of the through holes are enclosed together to form accommodating spaces, and the accommodating spaces or the transparent test tubes are used for accommodating cells and liquid medicine;
The plate body comprises a mounting part and a central part, wherein the mounting part surrounds the periphery of the central part, the through holes are formed in the central part, a sealing groove surrounding the central part is formed in the mounting part, when the cover body is covered on the plate body, the cover body part stretches into the sealing groove, and the sealing groove is used for containing liquid so that the joint of the cover body and the plate body is filled with the liquid and sealed;
The cover body comprises a top plate and a side plate, the side plate is connected around the top plate, the side plate is used for extending into the sealing groove, the axial projections of the through holes are projected on the top plate, the top plate comprises a fifth surface and a sixth surface which are opposite, the sixth surface faces the plate body, a plurality of concave lenses are arranged on the fifth surface, a plurality of convex lenses are arranged on the sixth surface, each concave lens and each convex lens correspond to each through hole on the plate body, the concave lenses and the convex lenses are matched to enlarge the cross section area of a light beam injected from the fifth surface on the sixth surface, and the light beam injected into the through holes covers a larger area;
The sixth surface is also provided with a plurality of steam absorbing pieces, each steam absorbing piece corresponds to one convex lens, each steam absorbing piece comprises a micro-channel, an inlet of each micro-channel is close to a mirror surface of each convex lens, and an outlet of each micro-channel is communicated with a water pumping hole arranged on each side plate;
The side plates are provided with the water pumping holes and the air inlet holes, the water pumping holes are used for being connected with water pumping equipment, the water pumping equipment is used for pumping out water vapor in the space between the cover body and the plate body, the air inlet holes are used for being connected with air inlet equipment, the air inlet equipment is used for providing environmental gas in the space between the cover body and the plate body, and the environmental gas is used for providing experimental environment for the cells;
the mounting part comprises a first surface, the first surface faces the direction of the cover body, and the sealing groove is formed in the first surface.
2. The cell well plate according to claim 1, wherein the mounting portion further comprises a second surface opposite to the first surface, the center portion comprises a third surface and a fourth surface opposite to each other, the third surface faces the cover direction, the plurality of through holes penetrate the third surface and the fourth surface, the second surface is coplanar with the fourth surface, and a distance between the third surface and the fourth surface is larger than a distance between the first surface and the second surface in an axial direction of the through holes.
3. The cell well plate according to claim 2, wherein first and second grooves are formed in the fourth surface along the inner walls of the plurality of through holes in opposition, the first and second grooves being for mounting temperature measuring members for measuring the temperature inside the plurality of through holes.
4. The cell well plate according to claim 2, wherein a plurality of first connecting holes are formed in the first surface, a plurality of second connecting holes are formed in the second surface, the mounting portion further comprises a first side surface and a second side surface which are opposite to each other, the first side surface and the second side surface are connected with the first surface and the second surface, the first side surface and the second side surface are located on two sides of the central portion respectively, a plurality of third connecting holes are formed in the first side surface, a plurality of fourth connecting holes are formed in the second side surface, and the first connecting holes, the second connecting holes, the third connecting holes and the fourth connecting holes are all used for being connected with a connecting rod for driving the plate body to move.
5. The cell well plate according to claim 4, wherein the first connecting hole extends from the first surface toward the second surface without penetrating the second surface, a first sub-hole and a second sub-hole which are arranged in a first direction and are opposite to each other are formed in the outer periphery of the first connecting hole, a third sub-hole is formed in the bottom wall of the first connecting hole, the radius of the third sub-hole is not smaller than the distance from the first sub-hole to the center of the first connecting hole, a fourth sub-hole and a fifth sub-hole are further formed in the plate body on one side, which is close to the first surface, of the third sub-hole, the fourth sub-hole and the fifth sub-hole are formed in the outer periphery of the first connecting hole, the fourth sub-hole and the fifth sub-hole are communicated with the first connecting hole and the third sub-hole without penetrating the first surface, the fourth sub-hole and the fifth sub-hole are arranged opposite to the fifth sub-hole and are arranged in the second direction, and the first direction and the second direction are not parallel.
6. The cell pore plate according to claim 1, wherein a hole shielding structure is arranged on the side plate around the water pumping hole and used for shielding the water pumping hole, the hole shielding structure comprises a supporting rod, an operating rod, a pressing plate, a sliding plate and a sliding rod, one end of the supporting rod is fixed on the side plate, the operating rod is elastically connected to the supporting rod in a rotating mode, the pressing plate comprises a first flat plate and a second flat plate, the extending direction of the first flat plate and the extending direction of the second flat plate form an included angle, the first end of the first flat plate is fixedly connected with the operating rod, the second end, opposite to the first end, of the first flat plate is connected with the second flat plate, the operating rod is elastically abutted against the supporting rod, so that the second flat plate is attached to the side plate, a mounting groove is formed in the pressing plate, the sliding plate is accommodated in the mounting groove and covers the water pumping hole, the pressing plate is pressed on the side plate, the sliding plate is provided with a sliding groove, the sliding rod is accommodated in the sliding groove and is connected to the sliding plate through the sliding rope, and the sliding plate is connected with the sliding plate in the sliding rope in a connecting mode.
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| CN201811319964.7A CN109337814B (en) | 2018-11-07 | 2018-11-07 | Cell well plate |
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| CN201811319964.7A CN109337814B (en) | 2018-11-07 | 2018-11-07 | Cell well plate |
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| US11492581B2 (en) * | 2019-04-17 | 2022-11-08 | Academia Sinica | Microwell device and method of manufacturing the same |
| WO2021223150A1 (en) * | 2020-05-07 | 2021-11-11 | 元锦生物科技股份有限公司 | Container for adjusting distribution of liquid and method thereof |
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