Co-culture device based on microfluidic organ chip

Abstract

The utility model discloses a co-culture device based on a microfluidic organ chip, which is characterized by comprising an upper-layer box body, a lower-layer box body detachably connected with the upper-layer box body, and an upper cover movably connected with the upper-layer box body, an upper-layer chip groove and an upper-layer pipe frame are arranged at the bottom in the upper-layer box body, the upper-layer chip groove is a through groove communicated with the upper-layer box body and the lower-layer box body, and an upper-layer liquid inlet and outlet hole and an upper-layer air inlet and outlet hole are formed in the side edge of the upper-layer box body; a lower-layer chip groove and a lower-layer pipe frame are arranged at the bottom in the lower-layer box body, and a lower-layer liquid inlet and outlet hole and a lower-layer air inlet and outlet hole are formed in the side edge of the lower-layer box body; the chip grooves are respectively arranged in the upper-layer box body and the lower-layer box body, and different gas environments are arranged in the upper-layer box body and the lower-layer box body, so that the co-culture of microorganisms and cells is realized, the operation steps are simplified, and the experiment efficiency is improved.

Description

TECHNICAL FIELD

[0001] The utility model relates to micro -fluidic technique field, concretely is a kind of co-culture device based on micro -fluidic organ chip. BACKGROUND

[0002] Microorganism and cell co-culture in simulated gas environment in human body is an important way to study the growth, metabolism and interaction of microorganism and cell in human body.

[0003] At present, micro -fluidic organ chip is used to simulate the microenvironment of human organ, and different environment microchannels, microvalves and micropumps are connected, and the components are numerous and the operation is cumbersome, so as to cause low experimental efficiency.

[0004] It should be noted that the information disclosed in the above BACKGROUND section is only intended to strengthen the understanding of the background of the present application, and therefore can include information that does not constitute prior art known to those of ordinary skill in the art. CONTENT OF THE UTILITY MODEL

[0005] In order to overcome the shortcomings of the prior art, the purpose of the utility model is to provide a co-culture device based on micro -fluidic organ chip, by setting chip groove in upper layer box and lower layer box respectively, and setting different gas environment for upper layer box and lower layer box, the co-culture of microorganism and cell is realized, the operation steps are simplified, and the experimental efficiency is improved.

[0006] To achieve the above purpose, the utility model provides the following technical scheme:

[0007] A co-culture device based on micro -fluidic organ chip, including upper layer box, with the detachable connection of the lower layer box of the upper layer box, with the movable connection of the upper cover of the upper layer box;The inner bottom of the upper layer box is provided with upper layer chip groove and upper layer pipe rack, the upper layer chip groove is the through groove that communicates the upper layer box and the lower layer box, and the side of the upper layer box is provided with upper layer inlet and outlet liquid hole and upper layer inlet and outlet gas hole;The inner bottom of the lower layer box is provided with lower layer chip groove and lower layer pipe rack, and the side of the lower layer box is provided with lower layer inlet and outlet liquid hole and lower layer inlet and outlet gas hole.

[0008] In some embodiments, the upper layer box is provided with palladium catalyst oxygen removal box.

[0009] In some embodiments, the upper layer box is detachably provided with a sealing strip around one side close to the upper cover, an upper layer locking member is arranged on the outer side surface of the side close to the upper cover of the upper layer box, and an upper layer buckle is arranged on the upper cover at a position corresponding to the upper layer locking member; the lower layer box is detachably provided with a sealing strip around one side close to the upper layer box, a lower layer locking member is arranged on the outer side surface of the side close to the upper layer box of the lower layer box, and a lower layer buckle is arranged on the outer side of the upper layer box at a position corresponding to the lower layer locking member.

[0010] In some embodiments, a peristaltic pump and a control valve are further included, and a fluid pipe is arranged to communicate the peristaltic pump and the control valve.

[0011] In some embodiments, the control valve is a three-way valve.

[0012] In some embodiments, a gas cylinder group and a gas pipe are further included.

[0013] In some embodiments, the gas cylinder group includes a carbon dioxide gas cylinder and a mixed gas cylinder, the mixed gas cylinder is communicated with the upper layer gas inlet and outlet hole through the gas pipe, and the carbon dioxide gas cylinder is communicated with the lower layer gas inlet and outlet hole through the gas pipe.

[0014] In some embodiments, a detection mechanism is further included, and the detection mechanism includes a detection electrode.

[0015] In some embodiments, an upper layer collection pipe is inserted into the upper layer pipe rack, and a lower layer collection pipe is inserted into the lower layer pipe rack.

[0016] In some embodiments, a temperature control mechanism is further included, and the temperature control mechanism includes a temperature control screen and a power supply assembly electrically connected to the temperature control screen.

[0017] Compared with the prior art, the utility model has the beneficial effects that:

[0018] By arranging the chip grooves in the upper layer box and the lower layer box respectively, and arranging different gas environments in the upper layer box and the lower layer box, the co-culture of microorganisms and cells is realized, the operation steps are simplified, and the experimental efficiency is improved.

[0019] Further, the pipe racks arranged in the upper layer box and the lower layer box can store the co-culture effluent collection pipes, and facilitate subsequent detection.

[0020] Further, the gas cylinder group and the peristaltic pump are arranged in the co-culture device, and the co-culture experimental device is further integrated, so that the experimental operation is more convenient.

[0021] Further, the detection mechanism is arranged in the co-culture device, the experimental effluent can be detected in real time, and the experimental efficiency is improved.

[0022] Further, the temperature control mechanism is arranged in the co-culture device, so that the temperature in the co-culture device can be monitored in real time, constant temperature control and temperature visualization are realized, and the experimental efficiency is further improved. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 It is a front perspective structural schematic view of one embodiment of the utility model.

[0024] Figure 2 It is a back perspective structural schematic view of one embodiment of the utility model.

[0025] Figure 3 It is a perspective structural schematic view of another embodiment of the utility model.

[0026] Figure 4 It is a perspective structural schematic view in the upper layer box of another embodiment of the utility model.

[0027] Figure 5 It is a top view structural schematic view of the lower layer box of another embodiment of the utility model.

[0028] Figure 6 It is a back perspective structural schematic view of another embodiment of the utility model.

[0029] In the drawing: 100, upper layer box; 110, upper cover; 111, upper layer buckle; 120, upper layer chip slot; 130, upper layer pipe rack; 131, upper layer collection pipe; 140, upper layer in-out liquid hole; 150, upper layer in-out gas hole; 160, palladium catalyst oxygen removal box; 170, sealing strip; 180, upper layer locking piece; 190, lower layer buckle; 200, lower layer box; 210, lower layer chip slot; 220, lower layer pipe rack; 221, lower layer collection pipe; 230, lower layer in-out liquid hole; 240, lower layer in-out gas hole; 250, lower layer locking piece; 300, peristaltic pump; 310, fluid pipe; 400, control valve; 500, gas cylinder group; 510, gas pipe; 520, carbon dioxide gas cylinder; 530, mixed gas cylinder; 600, detection mechanism; 610, electrode; 700, temperature control mechanism; 710, temperature control screen; 720, power supply assembly. DETAILED DESCRIPTION

[0030] The technical solutions in the embodiments of the utility model will be clearly and completely described below with reference to the drawings in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, rather than all the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the utility model.

[0031] Please refer to Figures 1-2The embodiment provides a co-culture device based on a micro-fluidic organ chip, Figure 1 A front perspective structure schematic diagram of one embodiment of the utility model is shown, Figure 2 A back perspective structure schematic diagram of one embodiment of the utility model is shown.

[0032] In one embodiment, a co-culture device based on a micro-fluidic organ chip comprises an upper box body 100, a lower box body 200 detachably connected with the upper box body 100, and an upper cover 110 movably connected with the upper box body 100.

[0033] The detachable connection mode between the upper box body 100 and the lower box body 200 is not limited in the embodiment of the application, for example, the bottom of the upper box body 100 directly contacts the top of the lower box body 200; the movable connection mode between the upper box body 100 and the upper cover 110 is not limited in the embodiment of the application, for example, the upper box body 100 is hingedly connected with the upper cover 110.

[0034] An upper chip groove 120 and an upper pipe rack 130 are arranged on the inner bottom of the upper box body 100, the upper chip groove 120 is a through groove connecting the upper box body 100 and the lower box body 200, and an upper liquid inlet and outlet hole 140 and an upper gas inlet and outlet hole 150 are arranged on the side of the upper box body 100.

[0035] The number of the upper chip groove 120 is not limited in the embodiment of the application, for example, six upper chip grooves 120 are arranged; the pore diameter of the accommodation cavity in the upper pipe rack 130 is not limited in the embodiment of the application, a plurality of accommodation cavities with different pore diameters can be arranged in the upper pipe rack 130, or only one kind of accommodation cavity with a certain pore diameter can be arranged, that is, the upper pipe rack 130 can accommodate a plurality of specifications of collection tubes, or can accommodate a certain specification of collection tubes, for example, the upper pipe rack 130 is a pipe rack accommodating 1.5ml collection tubes; the arrangement mode of the upper pipe rack 130 in the upper box body 100 is not limited in the embodiment of the application, for example, the upper pipe rack 130 can be inserted into the bottom of the upper box body 100 or fixedly arranged on the bottom of the upper box body 100; the upper chip groove 120 is a through groove connecting the upper box body 100 and the lower box body 200, when used, the organ chip is put in, so that the upper box body 100 and the lower box body 200 are relatively independent; the number of the single side of the upper liquid inlet and outlet hole 140 needs to be not less than twice the number of the upper chip groove 120, for example, twelve upper liquid inlet and outlet holes 140 are arranged; the upper gas inlet and outlet hole 150 is arranged on the side of the upper box body 100, and the number of the upper gas inlet and outlet hole 150 is more than two.

[0036] A lower chip groove 210 and a lower pipe rack 220 are arranged on the inner bottom of the lower box body 200, and a lower liquid inlet and outlet hole 230 and a lower gas inlet and outlet hole 240 are arranged on the side of the lower box body 200.

[0037] The number of the lower chip grooves 210 is not limited in the embodiments of the present application, for example, six lower chip grooves 210 are provided; the hole diameter of the accommodating cavity in the lower tube rack 220 is not limited in the embodiments of the present application, the lower tube rack 220 can be provided with accommodating cavities of multiple hole diameters, or can be provided with only one kind of accommodating cavities, that is, the lower tube rack 220 can accommodate collecting tubes of multiple specifications, or can accommodate collecting tubes of a certain specification, for example, the lower tube rack 220 is a tube rack accommodating 1.5ml collecting tubes; the arrangement of the lower tube rack 220 in the lower box body 200 is not limited in the embodiments of the present application, for example, the lower tube rack 220 can be inserted at the bottom of the lower box body 200, or can be fixedly arranged at the bottom of the lower box body 200; the lower chip groove 210 can be a through groove or a non-through groove, which is not limited in the embodiments of the present application, and in use, the lower chip groove 210 is relatively independent due to the placement of the organ chip; the number of the single side of the lower liquid inlet and outlet holes 230 needs to be not less than twice the number of the lower chip grooves 210, for example, twelve lower liquid inlet and outlet holes 230 are provided; the position of the lower gas inlet and outlet holes 240 needs to be arranged at the side of the lower box body 200, and the number of the lower gas inlet and outlet holes 240 needs to be not less than two.

[0038] In one embodiment, the upper box body 100 is provided with a palladium catalyst oxygen removal box 160, and the arrangement of the palladium catalyst oxygen removal box 160 is not limited in the embodiments of the present application, for example, the palladium catalyst oxygen removal box 160 can be detachably placed in the upper box body 100, and in use, the palladium catalyst oxygen removal box 160 is used to store palladium catalyst.

[0039] In one embodiment, the upper box body 100 is detachably provided with a sealing strip 170 around the side close to the upper cover 110, the outer side surface of the side close to the upper cover 110 of the upper box body 100 is provided with an upper locking member 180, and the side surface of the upper cover 110 is provided with an upper buckle 111 at a position corresponding to the upper locking member 180.

[0040] The upper locking member 180 and the upper buckle 111 are engaged, the sealing strip 170 between the upper box body 100 and the upper cover 110, and cooperate with the organ chip, so that the upper box body 100 is relatively sealed and independent, that is, except for the gas inlet of the upper gas inlet and outlet hole 150, the upper box body 100 has no gas exchange with the environment.

[0041] The lower box body 200 is detachably provided with a sealing strip 170 around the side close to the upper box body 100, the outer side surface of the side close to the upper box body 100 of the lower box body 200 is provided with a lower locking member 250, and the outer side of the upper box body 100 is provided with a lower buckle 190 at a position corresponding to the lower locking member 250.

[0042] The lower layer locking piece 250 is engaged with the lower layer buckle 190, the sealing strip 170 between the lower layer box 200 and the upper layer box 100 is matched with the organ chip, and the lower layer box 200 is relatively sealed and independent, that is, except for the air inlet of the lower layer air inlet and outlet hole 240, the lower layer box 200 has no gas exchange with the environment.

[0043] Please refer to Figures 3-6 , Figure 3 The figure shows the perspective structure schematic diagram of another embodiment of the utility model; Figure 4 The figure shows the perspective structure schematic diagram in the upper layer box 100 of another embodiment of the utility model; Figure 5 The figure shows the top view structure schematic diagram of another embodiment of the utility model lower layer box 200; Figure 6 The figure shows the back perspective structure schematic diagram of another embodiment of the utility model.

[0044] In another embodiment, the co-culture device further comprises a peristaltic pump 300, a control valve 400 and a fluid pipe 310 connecting the peristaltic pump 300 and the control valve 400.

[0045] In another embodiment, the control valve 400 is a three-way valve.

[0046] In another embodiment, the co-culture device further comprises a gas cylinder group 500 and a gas pipe 510 for providing the required gas for the co-culture device.

[0047] In another embodiment, the gas cylinder group 500 comprises a carbon dioxide cylinder 520 and a mixed gas cylinder 530, the mixed gas cylinder 530 stores 90% pure nitrogen, 5% carbon dioxide and 5% hydrogen mixed gas, the mixed gas cylinder 530 is connected to the upper layer air inlet and outlet hole 150 through the gas pipe 510, the carbon dioxide cylinder 520 is connected to the lower layer air inlet and outlet hole 240 through the gas pipe 510, after the mixed gas cylinder 530 is connected to the gas, the gas is discharged from another upper layer air inlet and outlet hole 150 to achieve the state of gas balance, similarly, after the carbon dioxide cylinder 520 is connected to the gas, the gas is discharged from another lower layer air inlet and outlet hole 240 to achieve the state of gas balance.

[0048] In another embodiment, the co-culture device further comprises a detection mechanism 600, the detection mechanism 600 comprises a detection electrode 610, and the part of the effluent of the co-culture device that needs to be detected is introduced into the detection electrode 610 by setting the control valve 400, and the detection is directly performed using the detection mechanism 600. Among them, the detection mechanism 600 can be a wireless signal transmission, and the detection result is transmitted to the terminal, or the detection result can be stored in the detection mechanism 600, and after the detection result, the detection data is transmitted to the terminal in a wired manner. Here, the embodiments of the present application are not limited.

[0049] In another embodiment, the upper pipe frame 130 is inserted into the upper collection pipe 131, and the lower pipe frame 220 is inserted into the lower collection pipe 221, which is used to receive the effluent of the part that needs to be detected, for example, to collect the bacterial metabolic liquid, and to be used for subsequent detection. Among them, the specification of the collection pipe 221 is not limited in the embodiments of the present application, for example, the collection pipe 221 is a 1.5ml centrifugal tube.

[0050] In another embodiment, the co-culture device further comprises a temperature control mechanism 700, the temperature control mechanism 700 comprises a temperature control screen 710 and a power supply assembly 720 electrically connected to the temperature control screen 710, which is used to control the temperature in the device, for example, to control the temperature in the device at a constant temperature of 37℃ to simulate the human body environment.

[0051] It should be noted that the material of the upper box body 100 and the lower box body 200 of the co-culture device is not limited in the present application, and preferably, the upper box body 100 and the lower box body 200 are transparent materials, which are convenient for observing the experimental process.

[0052] Further, in some other embodiments, the lower box body 200 and its internal structure can be provided in multiple groups for culturing more organ chips, and the fluid pipes 310 are used for liquid communication between the multiple lower box bodies 200, and the gas pipes 510 are used for gas supply, which will not be described here.

[0053] In use, the culture medium required for the experiment is configured in advance, the lower box 200 is placed on a table top, the upper box 100 is placed on the upper portion of the lower box 200, the organ chip is placed in the upper chip slot 120 and the lower chip slot 210 respectively, the palladium catalyst is placed in the palladium catalyst oxygen removal box 160, the liquid channel is connected by using the fluid pipe 310, the gas channel is connected by using the gas pipe 510, the power supply assembly 720 is connected, the temperature is set by the temperature control screen 710, the upper cover 110 is covered, the upper locking member 180 and the upper buckle 111 are buckled, the lower locking member 250 and the lower buckle 190 are buckled, the peristaltic pump 300 and the gas cylinder group 500 are started, and the experiment is started. The mixed gas containing a small amount of hydrogen is introduced into the upper box 100, the hydrogen reacts with the remaining trace oxygen to generate water by the catalytic action of the palladium catalyst, so that the oxygen removal purpose is achieved, so that the upper layer can be ensured to be in a completely anaerobic state, the anaerobic environment for the life of the human intestinal microorganism is simulated, the mixed gas introduced into the upper layer is discharged from another upper layer gas inlet and outlet hole, the gas balance state is achieved, the lower incubator is connected with the carbon dioxide gas cylinder, the gas environment in which the human intestinal cells are located is simulated, the carbon dioxide gas is discharged from the lower layer gas inlet and outlet hole, and the gas balance state is achieved. The liquid in the upper collecting pipe 131 and the lower collecting pipe 221 is observed, the experimental data of the receiving detection mechanism 600 are received, and subsequent experimental processing is performed.

[0054] It should be noted that the upper box 100 forms an oxygen-free environment for culturing anaerobic microorganisms, and the lower box 200 forms an aerobic environment for culturing aerobic cells.

[0055] The above only describes preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can be variously changed and modified. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A co-culture device based on microfluidic organ-on-a-chip, characterized in that, It includes an upper box (100), a lower box (200) detachably connected to the upper box (100), and an upper cover (110) movably connected to the upper box (100); The upper box (100) is provided with an upper chip slot (120) and an upper tube rack (130) at the bottom. The upper chip slot (120) is a through slot connecting the upper box (100) and the lower box (200). The upper box (100) is provided with an upper liquid inlet / outlet hole (140) and an upper air inlet / outlet hole (150) on its side. The lower housing (200) is provided with a lower chip slot (210) and a lower tube rack (220) at the bottom. The lower housing (200) is provided with a lower liquid inlet / outlet hole (230) and a lower air inlet / outlet hole (240) on the side.

2. The co-culture device based on microfluidic organ-on-a-chip according to claim 1, characterized in that, The upper box (100) is equipped with a palladium catalyst deoxygenation box (160).

3. The co-culture device based on microfluidic organ-on-a-chip according to claim 1, characterized in that, The upper housing (100) has a detachable sealing strip (170) around the perimeter of the side near the upper cover (110). The upper housing (100) has an upper locking member (180) on the outer surface of the side near the upper cover (110). The upper cover (110) has an upper buckle (111) at the corresponding position of the upper locking member (180). The lower housing (200) has a detachable sealing strip (170) around the side of the upper housing (100) near the upper housing (100). The lower housing (200) has a lower locking member (250) on the outer surface of the side of the lower housing (200) near the upper housing (100). The upper housing (100) has a lower buckle (190) at the position corresponding to the lower locking member (250) on the outer side.

4. The co-culture device based on microfluidic organ-on-a-chip according to claim 1, characterized in that, It also includes a peristaltic pump (300) and a control valve (400) and a fluid conduit (310) connecting the peristaltic pump (300) and the control valve (400).

5. A co-culture device based on microfluidic organ-on-a-chip according to claim 4, characterized in that, The control valve (400) is a three-way valve.

6. A co-culture device based on microfluidic organ-on-a-chip according to claim 1, characterized in that, It also includes a gas cylinder assembly (500) and a gas tube (510).

7. A co-culture device based on microfluidic organ-on-a-chip according to claim 6, characterized in that, The gas cylinder group (500) includes a carbon dioxide cylinder (520) and a mixed gas cylinder (530). The mixed gas cylinder (530) is connected to the upper air inlet / outlet (150) through the gas pipe (510), and the carbon dioxide cylinder (520) is connected to the lower air inlet / outlet (240) through the gas pipe (510).

8. A co-culture device based on microfluidic organ-on-a-chip according to claim 1, characterized in that, It also includes a detection mechanism (600), which includes a detection electrode (610).

9. A co-culture device based on microfluidic organ-on-a-chip according to claim 1, characterized in that, The upper collection pipe (131) is inserted into the upper pipe rack (130), and the lower collection pipe (221) is inserted into the lower pipe rack (220).

10. A co-culture device based on microfluidic organ-on-a-chip according to claim 1, characterized in that, It also includes a temperature control mechanism (700), which includes a temperature control screen (710) and a power supply component (720) electrically connected to the temperature control screen (710).

Images