Biological reaction system
By introducing the fluid injection flow channel and the fluid extraction flow channel of the fixture into the biological reaction system, combined with the infusion device, the problem of difficulty in discharge of waste liquid in the prior art is solved, more efficient waste liquid removal is achieved, and the environmental quality of biological cell culture is improved.
Patent Information
- Application Number
- PCT/CN2024/080616
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-12-27
- Filing Date
- 2024-03-07
- Publication Date
- 2025-07-03
AI Technical Summary
During the liquid change process of existing biological reaction systems, the pumping pressure of the infusion device makes it difficult for the cavity liquid to flow back to the capillary, making it difficult for waste liquid to be discharged, affecting the creation of the biological cell culture environment.
A biological reaction system is designed to connect the microfluidic chip and the infusion device through the liquid injection flow channel and the liquid extraction flow channel of the fixture. The liquid in the microfluidic chip is flowed into the fixture storage tank by using the infusion device, and waste liquid is discharged through the liquid extraction flow channel to improve the waste liquid discharge rate.
The waste liquid discharge rate is improved, a better biological cell culture environment is created, and the smooth progress of the biological reaction process is ensured.
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Figure CN2024080616_03072025_PF_FP_ABST
Abstract
Description
Bioreactor system
[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on December 27, 2023, with application number 202311833578.0 and application name “Bioreactor System”, the entire contents of which are incorporated by reference into this application. Technical Field
[0002] The present application relates to the field of biological culture technology, and in particular to a biological reaction system. Background Art
[0003] Currently, biological reactions are conducted in a bioreactor system culture environment, such as organ cell culture, tumor cell culture, and cell-drug tolerance experiments. Generally, a bioreactor system comprises a microfluidic chip, a fixture, and an infusion device. The microfluidic chip is equipped with capillaries and a cavity. The cavity is used for conducting the biological reaction, and the capillaries are used to transport the liquid required for the biological reaction into the cavity. The microfluidic chip is secured by a fixture, which is equipped with a flow channel that connects the capillaries of the microfluidic chip and the infusion device. The infusion device replaces the liquid in the capillaries through this flow channel, thereby continuously transporting the liquid required for the biological reaction into the cavity. The inventors have discovered that in this liquid exchange method, due to the pump pressure of the infusion device, the liquid in the cavity has difficulty flowing back into the capillaries. As a result, during the liquid exchange process, only the liquid in the capillaries is replaced, while the waste liquid generated during the biological reaction is not discharged, making it difficult to create a good environment for the biological reaction.
[0004] Application Contents
[0005] The main purpose of the embodiments of the present application is to provide a bioreactor system for discharging waste liquid left over from a microfluidic chip during a biological cell culture process, thereby creating a better biological cell culture environment.
[0006] In a first aspect, an embodiment of the present application provides a bioreaction system, comprising: a microfluidic chip, a fixture, and an infusion device;
[0007] The clamp comprises: a clamp body and a fixing assembly, a first surface of the clamp body is provided with a receiving groove, a second surface of the clamp body is opposite to the first surface, the receiving groove is used to place the microfluidic chip, the clamp body is further provided with an injection channel and a liquid extraction channel, a first end of the injection channel is used to transport liquid to the microfluidic chip, and liquid discharged from the microfluidic chip flows into the receiving groove, the receiving groove is connected to the first end of the liquid extraction channel; the fixing assembly is provided on the clamp body, and is used to fix the microfluidic chip in the receiving groove;
[0008] An infusion device is connected to the second end of the injection channel and the second end of the extraction channel respectively, and is used to replace the liquid in the microfluidic chip.
[0009] An embodiment of the present application provides a bioreactor system, which includes: a microfluidic chip, a fixture and an infusion device, the fixture includes: a fixture body and a fixing component, the first surface of the fixture body is provided with a receiving groove, the second surface of the fixture body is opposite to the first surface, the receiving groove is used to place the microfluidic chip, the fixture body is also provided with an injection channel and a liquid extraction channel, the first end of the injection channel is used to transport liquid to the microfluidic chip, the liquid discharged from the microfluidic chip flows into the receiving groove, and the receiving groove is connected to the first end of the liquid extraction channel; the fixing component is provided on the fixture body, and is used to fix the microfluidic chip in the receiving groove; the infusion device is connected to the second end of the injection channel and the second end of the liquid extraction channel, respectively, and is used to replace the liquid in the microfluidic chip. In the bioreactor system provided in the embodiment of the present application, the perfusion device transports liquid to the microfluidic chip through the injection channel of the clamp, and the liquid flowing out of the microfluidic chip flows into the receiving tank of the clamp. The liquid in the receiving tank is extracted by the perfusion device through the extraction channel, thereby discharging waste liquid generated during the biological cell culture process and remaining in the microfluidic chip. Compared with the microfluidic chip discharging liquid only from its own liquid outlet, the waste liquid discharge rate is higher, which can create a better biological cell culture environment. BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG1 is a schematic structural diagram of a bioreactor system provided in an embodiment of the present application;
[0011] FIG2 is a schematic structural diagram of a microfluidic chip provided in an embodiment of the present application;
[0012] FIG3 is a schematic structural diagram of a fixture for a microfluidic chip provided in an embodiment of the present application;
[0013] FIG4 is a schematic structural diagram of a fixture for a microfluidic chip provided in an embodiment of the present application;
[0014] FIG5 is a schematic cross-sectional view of a clamp provided in an embodiment of the present application;
[0015] FIG6 is a schematic diagram of a half-section structure of a clamp body provided in an embodiment of the present application;
[0016] FIG7 is a schematic structural diagram of a clamp provided in an embodiment of the present application;
[0017] FIG8 is a schematic diagram of a half-section structure of a clamp body provided in an embodiment of the present application;
[0018] FIG9 is a bottom schematic diagram of a clamp provided in an embodiment of the present application;
[0019] FIG10 is a schematic diagram of a clamp provided in an embodiment of the present application;
[0020] FIG11 is a schematic diagram of a fixture for a microfluidic chip provided in an embodiment of the present application.
[0021] FIG12 is a schematic half-section view of a clamp provided in an embodiment of the present application along the center of two guide holes;
[0022] FIG13 is an exploded schematic diagram of a clamp provided in an embodiment of the present application;
[0023] FIG14 is an exploded schematic diagram of a clamp provided in an embodiment of the present application;
[0024] FIG15 is a schematic structural diagram of a perfusion device provided in an embodiment of the present application;
[0025] FIG16 is a partial structural diagram of a perfusion device provided in an embodiment of the present application;
[0026] FIG17 is an exploded schematic diagram of a perfusion device provided in an embodiment of the present application;
[0027] FIG18 is a schematic structural diagram of a first clamping assembly provided in an embodiment of the present application;
[0028] FIG19 is a schematic structural diagram of a first clamping assembly provided in an embodiment of the present application;
[0029] FIG20 is a schematic structural diagram of a second clamping assembly provided in an embodiment of the present application;
[0030] FIG21 is a schematic structural diagram of a second clamping assembly provided in an embodiment of the present application;
[0031] FIG22 is a schematic structural diagram of a combination of a first clamping assembly and a second clamping assembly provided in an embodiment of the present application;
[0032] FIG23 is a schematic structural diagram of a first fixing member provided in an embodiment of the present application;
[0033] FIG24 is a schematic structural diagram of a second fixing member provided in an embodiment of the present application;
[0034] FIG25 is a schematic structural diagram of a clamp provided in an embodiment of the present application;
[0035] FIG26 is a schematic structural diagram of a bioreactor system provided in an embodiment of the present application;
[0036] FIG27 is a schematic structural diagram of a microfluidic chip provided in an embodiment of the present application;
[0037] Figure 28 is a cross-sectional schematic diagram of a capillary provided in an embodiment of the present application. DETAILED DESCRIPTION
[0038] It should be understood that the specific embodiments described herein are only used to explain the present application and are not intended to limit the present application.
[0039] In the subsequent description, suffixes such as "module," "component," or "unit" used to represent elements are used only to facilitate the description of the present application and have no specific meaning. Therefore, "module," "component," or "unit" may be used interchangeably.
[0040] The present application provides a bioreactor system comprising a microfluidic chip, a fixture, and an infusion device. The fixture comprises a fixture body and a fixing assembly. A first surface of the fixture body defines a receiving groove, and a second surface of the fixture body is opposite to the first surface. The receiving groove is used to accommodate the microfluidic chip. The fixture body further defines an injection channel and a liquid extraction channel. The first end of the injection channel is used to deliver liquid to the microfluidic chip. Liquid discharged from the microfluidic chip flows into the receiving groove, which is connected to the first end of the liquid extraction channel. The infusion device is connected to the second end of the injection channel and the second end of the liquid extraction channel, respectively, for replacing liquid in the microfluidic chip.
[0041] As shown in Figure 1, the bioreactor system 400 includes a fixture 100 and a perfusion device 300. The perfusion device 300 includes a first perfusion device 31, a second perfusion device 32, and a perfusion pump 39. The perfusion pump 39 drives one of the first perfusion device 31 and the second perfusion device 32 to pump liquid and the other to inject liquid. The first perfusion device 31 and the second perfusion device 32 are connected to the fixture 100 via a connecting tube 41. The fixture 100 includes a fixture body 11. In this embodiment, the two connecting tubes 41 each include an infusion tube and a needle. One end of one infusion tube is connected to one perfusion device, and the other end is connected to the injection channel of the fixture 100 via a needle. The other end of the infusion tube is connected to the other perfusion device, and the other end is connected to the extraction channel of the fixture 100 via a needle. For example, the first perfusion device 31 is used for pumping liquid, and the second perfusion device 32 is used for injecting liquid.
[0042] As shown in Figure 2, the microfluidic chip 300 includes a chip body 31, a cavity 32, and a capillary 33. The opening of the cavity 32 is located on the second surface M2 of the chip body 31, and the capillary 33 is located in the cavity 32. The third surface F3 of the chip body 31 also defines a liquid inlet 311 and a liquid outlet 312, through which the capillary 33 can exchange liquid. The second surface M2 of the chip body 31 is opposite to the first surface M1, and the third surface M3 of the chip body 31 is perpendicular to the first surface M1 and the second surface M2 of the chip body 31.
[0043] As shown in FIG3 , the fixture 100 includes a fixture body 11 and a fixing assembly 12 . The fixing assembly 12 is used to fix the microfluidic chip 300 in the fixture body 11 .
[0044] Exemplarily, the fixture 100 is placed horizontally during use, with the first surface F1 of the fixture body 11 facing downward and toward the bottom of the accommodating cavity, that is, the first surface F1 of the fixture body 11 is the bottom surface of the fixture body 11, and the second surface F2 of the fixture body 11 is facing upward, that is, the second surface F2 of the fixture body 11 is the top surface. When the microfluidic chip 300 is fixed to the fixture 100, the first surface M1 of the chip body 31 is placed downward, that is, the first surface M1 of the chip body 31 is the bottom surface of the microfluidic chip 300, and the first surface M1 of the chip body 31 is placed upward, that is, the first surface M1 of the chip body 31 is the top surface. It should be noted that the chip body 31 is the main part of the microfluidic chip 300, and the first surface M1, second surface M2 and third surface M3 of the chip body 31 can also serve as the first surface M1, second surface M2 and third surface M3 of the microfluidic chip 300.
[0045] As shown in FIG4 , the fixing assembly 12 is disposed on the fixture body 11 and is used to secure the microfluidic chip 300 in the receiving groove 111. The first surface F1 of the fixture body 11 defines a receiving groove 111. The receiving groove 111 is used to accommodate the microfluidic chip 300 shown in FIG2 . The cavity 32 of the microfluidic chip 300 communicates with the receiving groove 111, and liquid flowing out of the opening of the cavity 32 flows into the receiving groove 111. When liquid in the cavity 32 of the microfluidic chip 300 overflows the cavity 32, it flows into the receiving groove 111 through the connecting groove 112.
[0046] The two ends of the receiving groove 111 are used to limit the two ends of the microfluidic chip 300, and one end of the receiving groove 111 is also used to install the fixing assembly 12. When the fixing assembly 12 is in the extended state, it facilitates the placement of the microfluidic chip 300 in the receiving groove 111; when the fixing assembly 12 is in the reset state, it can secure the microfluidic chip 300 placed in the receiving groove 111.
[0047] As shown in FIG5 , the fixture body 11 is provided with an injection channel 114. The first end of the injection channel 114 is used to connect to the second injector 32 shown in FIG1 , and the second end of the injection channel 114 is used to connect to the liquid inlet 311 of the microfluidic chip 300. The first end of the injection channel 114 is disposed on the second surface F2 of the fixture body 11, and the second end of the injection channel 114 is disposed on the sidewall of the receiving groove 111, which sidewall is aligned with the third surface M3 of the microfluidic chip 300. When the microfluidic chip 300 is secured in the receiving groove 111, the second end of the injection channel 114 is connected to the liquid inlet 311 of the microfluidic chip 300. A sealing member, such as a rubber ring or a silicone ring, is also provided at the second end of the injection channel 114 to ensure sealing between the second end of the injection channel 114 and the liquid inlet 311 of the microfluidic chip 300.
[0048] As shown in FIG6 , the fixture body 11 defines a liquid extraction channel 115, the first end of which is located on the second surface F2 of the fixture body 11. The second end of the liquid extraction channel 115 communicates with the receiving tank 111 (the figure shows the area where the receiving tank 111 is located).
[0049] The first end of the liquid extraction channel 115 is disposed on the second surface F2 of the fixture body 11 and is configured to connect to the first syringe 31 shown in FIG1 . The second end of the liquid extraction channel 115 is connected to the receiving tank 111 and is configured to extract liquid from the receiving tank 111 via the first syringe 31 to lower the liquid level in the receiving tank 111 when the liquid level in the receiving tank 111 reaches a predetermined height.
[0050] In the bioreactor system provided in the embodiment of the present application, the perfusion device transports liquid to the microfluidic chip through the injection channel of the clamp, and the liquid flowing out of the microfluidic chip flows into the receiving tank of the clamp. The liquid in the receiving tank is extracted by the perfusion device through the extraction channel, thereby discharging waste liquid generated during the biological cell culture process and remaining in the microfluidic chip. Compared with the microfluidic chip discharging liquid only from its own liquid outlet, the waste liquid discharge rate is higher, which can create a better biological cell culture environment.
[0051] In order to more clearly introduce the technical solution of the present application, the technical solution of the present application will be introduced through specific embodiments below. It should be noted that the specific embodiments are used to expand the technical solution of the present application, but are not intended to limit the present application.
[0052] As shown in Figure 7, the fixture 100 also includes a tray 14, which is used to place the fixture body 11. The fixture 11 is placed in the receiving cavity provided by the tray 14, wherein one tray 14 can place multiple fixture bodies 11, and the tray 14 is used to provide a separate receiving cavity for each fixture body 11. The fixture body 11 is used to place the microfluidic chip 300. After the liquid in the microfluidic chip 300 flows out, it flows into the receiving cavity provided by the tray 14. Since the first surface F1 of the fixture body 11 faces the bottom of the receiving cavity, that is, the opening of the receiving groove 111 is facing the receiving cavity, the liquid gathers in the receiving cavity, which is equivalent to gathering in the receiving groove 111. After gathering to a certain height, it is drawn away by the first injector 31 as shown in Figure 1.
[0053] In some embodiments, as shown in FIG4 , the first surface F1 of the clamp body 11 further defines a connecting groove 112. The connecting groove 112 is connected to the receiving groove 111, and the depth of the connecting groove 112 is greater than the depth of the receiving groove 111. It should be noted that in this embodiment of the present application, the reference plane for the depth is the first surface F1 of the clamp body 11.
[0054] As shown in FIG. 5 , the liquid in the microfluidic chip 300 overflows from the opening of the cavity 32 and is discharged through the communicating groove 112 .
[0055] In the embodiment of the present application, the receiving tank 111 and the cavity 32 of the microfluidic chip 300 are connected via the connecting groove 112 to ensure that the liquid can quickly flow into the receiving tank 111 after overflowing the cavity 32 .
[0056] In some embodiments, as shown in FIG. 4 , an observation hole 113 is further defined between the first surface F1 and the second surface F2 of the fixture body 11 , and the observation hole 113 is in communication with the receiving groove 111 .
[0057] The observation through hole 113 is used to provide light to the microfluidic chip 300 from the second surface F2 of the fixture body 11 . The observation through hole 113 also facilitates a user to remove a biological sample from the microfluidic chip 300 .
[0058] In some embodiments, as shown in FIG4 , the first surface F1 of the fixture body 11 further defines a liquid outlet groove 1114. The liquid outlet groove 1114 communicates with the receiving tank 111 at a sidewall of the receiving tank 111, which sidewall corresponds to the third surface M3 of the microfluidic chip 300. When the microfluidic chip 300 shown in FIG2 is placed in the receiving tank 111, the liquid outlet 312 of the microfluidic chip 300 is located within the receiving tank 111, and the liquid outlet 312 of the microfluidic chip 300 corresponds to the liquid outlet groove 1114. Liquid flowing out of the liquid outlet 312 can be discharged more quickly into the receiving tank 111 through the liquid outlet groove 1114.
[0059] In some embodiments, as shown in FIG. 4 , the first surface F1 of the clamp body 11 further defines an anti-overflow groove 116 , which is in communication with the accommodating groove 111 .
[0060] As shown in Figure 8, the dotted-line area illustrates the receiving groove 111, the anti-overflow groove 116, and the viewing hole 113. The anti-overflow groove 116 forms a stepped relationship with the receiving groove 111. The depth of the anti-overflow groove 116 is greater than that of the receiving groove 111, with the depth referenced by the first surface F1 of the fixture body 11. The depth difference between the anti-overflow groove 116 and the receiving groove 111 ranges from 0.5 mm to 3 mm. For example, the depth difference between the anti-overflow groove 116 and the receiving groove 111 is 1.7 mm.
[0061] Due to the capillary effect of the liquid, the liquid in the receiving tank 111 flows along the sidewalls of the receiving tank 111 toward the second end of the liquid extraction channel 115. When the liquid level in the receiving tank 111 does not reach the preset height, the second end of the liquid extraction channel 115 can still extract the liquid from the receiving tank 111. This abnormal liquid extraction phenomenon causes the liquid level in the receiving tank 111 to be insufficient, resulting in insufficient liquid storage in the microfluidic chip 300, and thus, the biological reaction conditions in the microfluidic chip 300 cannot be guaranteed.
[0062] In the embodiment of the present application, an anti-overflow groove 116 is provided at the second end of the liquid extraction channel 115, and there is a height difference between the anti-overflow groove 116 and the receiving tank 111. Therefore, when the liquid in the receiving tank 111 reaches the anti-overflow groove 116 due to capillary phenomenon, liquid droplets are first generated on the side wall of the anti-overflow groove 116. Under the action of gravity, most of the liquid droplets fall, thereby reducing the number of liquid droplets reaching the second end of the liquid extraction channel 115, thereby avoiding excessive extraction of liquid in the receiving tank 111 and improving the balance of the liquid replacement process.
[0063] In addition, it is also necessary to ensure that the distance between the second end of the liquid extraction channel 115 and the side wall of the anti-overflow groove 116 is 2 mm-5 mm to obtain a better anti-capillary effect.
[0064] As shown in FIG9 , the sidewall of the overflow prevention groove 116 includes an arc-shaped sidewall segment with the second end of the liquid extraction channel 115 as the center and a radius r. The value of r ranges from 2 mm to 5 mm. For example, r can be any one of 2.4 mm, 3.5 mm, or 4.5 mm. By limiting the distance between the second end of the liquid extraction channel 115 and the sidewall of the overflow prevention groove 116, liquid droplets generated by capillary action can drip before converging at the second end of the liquid extraction channel 115, thereby reducing the number of liquid droplets reaching the second end of the liquid extraction channel 115 and preventing excessive extraction of liquid from the receiving tank 111.
[0065] In some embodiments, as shown in Figure 5, the injection channel 114 includes at least a first injection channel section 1141 and a second injection channel section 1142 from the first end to the second end, the diameter of the first injection channel section 1141 is larger than the diameter of the second injection channel section 1142, and the connection between the first injection channel section 1141 and the second injection channel section 1142 is in the shape of a slope.
[0066] In some embodiments, as shown in Figure 6, the first end to the second end of the liquid pumping channel 115 includes at least a first liquid pumping channel section 1151 and a second liquid pumping channel section 1152, the diameter of the first liquid pumping channel section 1151 is larger than the diameter of the second liquid pumping channel section 1152, and the connection between the first liquid pumping channel section 1151 and the second liquid pumping channel section 1152 is in the shape of a slope.
[0067] Generally, the diameters of the injection channel 114 and the extraction channel 115 are the same as the diameter of the filling piece. However, such a configuration is not conducive to the insertion of the filling piece, not only reducing the operating efficiency, but also possibly bending the needle during the insertion process of the filling piece. Therefore, in the embodiment of the present application, the first end of the injection channel 114 and the first end of the extraction channel 115 are used to insert the filling piece. The diameter of the first injection channel section 1141 located at the first end of the injection channel 114 is larger than the diameter of the second injection channel section 1142. The diameter of the first extraction channel section 1151 located at the first end of the extraction channel 115 is larger than the diameter of the second extraction channel section 1152, so as to facilitate the insertion of the filling piece from the first end of the injection channel 114. At the same time, the embodiment of the present application also makes a bevel treatment at the connection between the first liquid injection channel section 1141 and the second liquid injection channel section 1142, and the first liquid extraction channel section 1151 and the second liquid extraction channel section 1152, so that the connection achieves a transition from large to small, thereby improving the passability of the filling parts at the connection, thereby improving the user's operating efficiency.
[0068] In some embodiments, the inclined surface includes a cone shape, and also includes other shapes from large to small, such as an arc shape. It should be noted that the inclined surface provided in the embodiments of the present application is only used to specifically introduce the embodiments and is not intended to limit the present application.
[0069] It should be noted that in the above embodiment, a seal is also provided at the first liquid injection channel section 1141 and the first liquid extraction channel section 1151. For example, the seal is a rubber ring or a silicone ring to ensure the sealing between the first liquid injection channel section 1141, the first liquid extraction channel section 1151 and the filling piece.
[0070] In some embodiments, as shown in FIG10 , the receiving tank 111 includes a first recessed portion 1111 and a second recessed portion 1112 extending along the side of the microfluidic chip 300. The first recessed portion 1111 is connected to the anti-overflow groove 116. The cross-sectional shape of the microfluidic chip 300 on the first surface M1 is rectangular, with the long sides of the rectangle forming the side edges of the microfluidic chip 300. This not only increases the liquid capacity of the receiving tank 111 but also makes it easier for the user to place the microfluidic chip 300 in the receiving tank 111.
[0071] In some embodiments, as shown in FIG10 , one end of the receiving groove 111 is further provided with a first fool-proofing portion 1113. Specifically, the first fool-proofing portion 1113 is provided at two corners of one end of the receiving groove 111, one of which is groove-shaped and the other is arc-shaped. The microfluidic chip 300 includes a second fool-proofing portion 213. Specifically, the second fool-proofing portion 213 is provided at two corners of one end of the microfluidic chip 300, one of which is a right angle and the other is inscribed. When the first fool-proofing portion 1113 and the second fool-proofing portion 213 cooperate, the inscribed corners of the microfluidic chip 300 can only be placed at the corners of the arc-shaped receiving groove 111, and the right-angled corners of the microfluidic chip 300 can only be placed at the groove-shaped receiving groove 111, thereby preventing the microfluidic chip 300 from being placed in reverse.
[0072] In some embodiments, as shown in FIG11 , a first connecting component 117 is provided on the second surface F2 of the fixture body 11. The fixture 100 also includes a fixture cover 13, which includes a second connecting component 131 and two guide holes 132. The second connecting component 131 is configured to connect to the first connecting component 117 of the fixture body 11. The fixture body 11 and the fixture cover 13 are connected to form a single unit via the first connecting component 117 and the second connecting component 131. The two guide holes 132 connect the second surface S2 and the first surface S1 of the fixture cover 13, with the second surface S2 and the first surface S1 of the fixture cover 13 facing each other.
[0073] The two guide holes 132 correspond to the first end of the liquid injection channel 114 and the first end of the liquid extraction channel 115 respectively.
[0074] As shown in Figure 12, the first end of guide hole 132 is located on the second side S2 of clamp cover 13, while the second end of guide hole 132 is located on the first side S1 of clamp cover 13. The first end of guide hole 132 is used to insert the potting element. After the clamp body 11 and clamp cover 13 are formed into a single unit, the second ends of the two guide holes 132 correspond to the first ends of the injection channel 114 and the first ends of the withdrawal channel 115, respectively.
[0075] The fixture cover 13 is used to reduce the amount of impurities that fall into the microfluidic chip 300 from the observation hole 113. The guide holes 132 on the fixture cover 13 can also assist the user in inserting the filling piece into the injection channel 114 and the extraction channel 115 to improve the user's operating efficiency.
[0076] In some embodiments, as shown in Figure 11, the first connecting component 117 includes: a first protrusion 1171 and a second protrusion 1172, and the second connecting component 131 includes: a first groove 1311 and a second groove 1312, and the first protrusion 1171 and the second protrusion 1172 are used to connect with the first groove 1311 and the second groove 1312 respectively.
[0077] Exemplarily, the first groove 1311 and the second groove 1312 have different sizes or shapes. The size and shape of the first groove 1311 are the same as the size and shape of the first protrusion 1171, and the size and shape of the second groove 1312 are the same as the size and shape of the second protrusion 1172. In this way, it is ensured that the first groove 1311 and the second groove 1312 cannot simultaneously reversely place the second protrusion 1172 and the first protrusion 1171, thereby preventing the clamp body 11 and the clamp cover 13 from reversing their mating.
[0078] It should be noted that the first connecting component 117 can also be provided on the clamp cover 13, and the second connecting component 131 can also be provided on the clamp body 11. The number and shape of the mating components of the first connecting component 117 and the second connecting component 131 are not fixed. The embodiments of this application are only for specific illustration and are not intended to limit this application.
[0079] In some embodiments, the first connecting component 117 and the second connecting component 131 cooperate to prevent the clamp cover 13 from being reversely connected to the clamp body 11 .
[0080] The exemplary first connecting component 117 and the second connecting component 131 can only form a match at one angle. Specifically, the first connecting component 117 includes: a first protrusion 1171 and a second protrusion 1172, and the second connecting component 131 includes: a first groove 1311 and a second groove 1312. The first groove 1311 and the second groove 1312 are different in size or shape. The size and shape of the first groove 1311 are the same as the size and shape of the first protrusion 1171, and the size and shape of the second groove 1312 are the same as the size and shape of the second protrusion 1172. In this way, it is ensured that the first groove 1311 and the second groove 1312 cannot simultaneously reverse the second protrusion 1172 and the first protrusion 1171.
[0081] In other embodiments, the first connecting assembly 117 and the second connecting assembly 131 can be machined into irregular shapes to achieve mating at only one angle. Furthermore, the number and form of mating components of the first connecting assembly 117 and the second connecting assembly can be adjusted to achieve mating at only one angle. The first connecting assembly 117 and the second connecting assembly 131 can also be mated using other existing foolproofing mechanisms, which will not be elaborated on here.
[0082] In some embodiments, as shown in FIG12 , from the second surface S2 to the first surface S1 of the fixture cover 13 , the guide hole 132 includes at least a first guide hole segment 1321 and a second guide hole segment 1322 , the diameter of the first guide hole segment 1321 is larger than the diameter of the second guide hole segment 1322 , and the connection between the first guide hole segment 1321 and the second guide hole segment 1322 is in the shape of a slope.
[0083] It should be noted that, in the above embodiment, sealing members, such as rubber rings, are further provided at the first guide hole section 1321 and the second guide hole section 1322 to ensure sealing between the first guide hole section 1321, the second guide hole section 1322 and the potting member.
[0084] The inclined surface includes a cone shape, and also includes other shapes from large to small, such as an arc shape. It should be noted that the inclined surface provided in the embodiments of the present application is only used to specifically introduce the embodiments, and is not intended to limit the present application.
[0085] In some embodiments, please refer to FIG13 , which illustrates an exploded view of a clamp provided by an embodiment of the present application. As shown in FIG13 , the fixing assembly 12 includes a sliding plate 121 and a spring 122. A sliding groove 1181 is defined on the second surface F2 of the clamp 100 body. The sliding groove 1181 faces the receiving groove 111. A spring hole 1182 is defined between the sliding groove 1181 and the receiving groove 111. The spring hole 1182 is used to mount the spring 122. The sliding plate 121 is U-shaped, with a portion of the sliding plate 121 positioned within the sliding groove 1181 and a portion positioned within the receiving groove 111. One end of the spring 122 is connected to the bottom of the U-shaped portion of the sliding plate 121, and the other end of the spring 122 is connected to the clamp 100 body. When an external force is applied to the sliding plate 121, the sliding plate 121 moves within the sliding groove 1181, facilitating placement of the microfluidic chip 300 within the receiving groove 111. After the microfluidic chip 300 is placed and the application of external force stops, the spring 122 resets the sliding piece 121 to clamp the microfluidic chip 300 .
[0086] In some embodiments, as shown in FIG14 , the fixing assembly 12 includes a spring 123. The spring 123 includes a fixing member 1231 and a paddle 1232. A fixing slot 119 is defined on the second surface F2 of the fixture 100 body. The sliding slot 1181 faces the fixing slot 119. The fixing slot 119 is used to mount the fixing member 1231, which is secured to the fixing slot 119 by screws. When an external force is applied to the paddle 1232, the paddle 1232 deforms to facilitate placement of the microfluidic chip 300 in the receiving slot 111. After the microfluidic chip 300 is placed and the external force is removed, the paddle 1232 automatically returns to secure the microfluidic chip 300. The spring 123 can be made of SUS304, SUS316, beryllium copper, or Teflon-coated carbon steel.
[0087] It should be noted that the embodiment of the fixing component 12 in the embodiment of the present application is only used to provide a detailed introduction to the fixture 100 of the microfluidic chip 300, and other existing forms of fixing components are all within the scope of the embodiment of the present application.
[0088] An embodiment of the present application provides a perfusion device for installing a syringe, which includes a receiving member and a piston member. Two groups of syringes are installed in the same direction on the perfusion device, one of the two groups of syringes being a first syringe and the other being a second syringe. That is, when the two groups of syringes are installed on the perfusion device, the relative positions of the receiving member and the piston member of each group of syringes are the same.
[0089] Referring to Figure 15 , as shown in Figure 15 , the perfusion device 100 includes a base 33, a drive assembly 34, a slider assembly 35, a first clamping assembly 36, and a second clamping assembly 37. The drive assembly 34 is mounted on the base 33. The slider assembly 35 is slidably connected to the drive assembly 34 and is used to drive the slider assembly 35. The first clamping assembly 36 is mounted on the slider assembly 35 and is used to secure the container 311 of at least one first syringe 31. The second clamping assembly 37 is mounted on the base 33 and is used to secure the container 321 of at least one second syringe 32. The slider assembly 35 includes a first fixing member 354, which is used to secure the piston 322 of the second syringe 32, and / or the base 33 includes a second fixing member 331, which is used to secure the piston 312 of the first syringe 31. The drive assembly 34 drives the slider assembly 35 to move, driving one of the first syringe 31 to pump liquid and the other to inject liquid. The bottom of the second fixing member 331 is provided with a waist-shaped hole that can be adjusted forward and backward to adapt to different brands and models of syringes.
[0090] In some embodiments, the slider assembly 35 is provided with a first fixing member 354, which is used to fix the piston member 322 of the second syringe 32, so that when the slider assembly 35 moves in the first direction, it pulls the piston member 322 of the second syringe 32. The container 321 of the second syringe 32 is fixed to the base 33. When the slider assembly 35 moves in the first direction, the second syringe 32 performs a liquid extraction function. The container 311 of the first syringe 31 is fixed to the slider assembly 35, and the piston member 312 of the first syringe 31 is supported by the second fixing member 331 on the base 33. When the slider assembly 35 moves in the first direction, it pushes the container 311 of the first syringe 31, and the second syringe 32 performs a liquid injection function.
[0091] In some embodiments, as shown in FIG15 , a first fixing member 354 is mounted on the side of the slider assembly 35 facing the second direction. The piston member 322 of the second syringe 32 includes a protrusion, and the first fixing member 354 is used to fix the protrusion of the piston member 322 of the second syringe 32. In this way, when the slider assembly 35 pushes the piston member 322 of the second syringe 32 to move in the first direction, the relative position of the slider assembly 35 and the piston member 322 of the second syringe 32 is maintained unchanged, thereby ensuring the accuracy of the movement of the piston member 322 of the second syringe 32 within the receiving member 321 of the second syringe 32, thereby improving the accuracy of liquid injection.
[0092] In other embodiments, the piston member 312 of the first syringe 31 is fixed to the second fixing member 331. When the slider assembly 35 pulls the receiving member 311 of the first syringe 31 in the second direction, the first syringe 31 performs a liquid extraction function. The receiving member 321 of the second syringe 32 is fixed to the base 33. When the slider assembly 35 pushes the piston member 322 of the second syringe 32 in the second direction, the liquid injection function is performed.
[0093] It should be noted that when the slider assembly 35 moves in the first direction, only the second fixing member 331 is provided, and the first fixing member 354 is not provided. Thus, one of the first and second syringes 31 and 32 can be simultaneously driven to perform a liquid extraction function, while the other performs a liquid injection function. When the slider assembly 35 moves in the second direction, only the first fixing member 354 is provided, and the second fixing member 331 is not provided. Alternatively, one of the first and second syringes 31 and 32 can be simultaneously driven to perform a liquid extraction function, while the other performs a liquid injection function.
[0094] In the perfusion device provided in the embodiment of the present application, the first clamping assembly is connected to the slider assembly, the container of the first syringe is fixed on the first clamping assembly, the piston of the first syringe is fixed on the second fixing piece of the base, the container of the first syringe is fixed on the second clamping assembly, the second clamping assembly is fixed on the base, and the piston of the second syringe is fixed on the second fixing piece of the slider assembly. Therefore, when the slider assembly moves, it will drive the container of the first syringe to move, and drive the piston of the second syringe to move, so that the two groups of syringes can realize the injection function and the liquid extraction function at the same time, reducing the number of perfusion devices required to realize the injection function and the liquid extraction function at the same time, saving space and equipment expenses, and at the same time, realizing equal or equal proportions of liquid extraction and injection.
[0095] Because the first and second syringes in the embodiment of the present application are installed in the same direction, the two syringes share the same longitudinal space, reducing the lateral space required for installation. This reduces the lateral space required for the syringe, thereby reducing the footprint of the syringe. The same orientation of the needles allows for more uniform drainage of the aspiration / injection pipelines.
[0096] In order to more clearly introduce the technical solution of the present application, the technical solution of the present application will be introduced through specific embodiments below. It should be noted that the specific embodiments are used to expand the technical solution of the present application, but are not intended to limit the present application.
[0097] In some embodiments, as shown in FIG16 , the drive assembly 34 includes a motor (not shown), a guide rod 341, and a drive screw 342. The base 33 includes a main base 332, a first support 333, and a second support 334. The first support 333 and the second support 334 are disposed opposite each other on the main base 332, and the ends of the guide rod 341 and the drive screw 342 are mounted on the first support 333 and the second support 334, respectively.
[0098] The motor is mounted on any one of the main base 332, the first support 333, and the second support 334. The motor is used to rotate the drive screw 342, which is also connected to the slider assembly 35 to drive the slider assembly 35. The base 33 also includes a transmission assembly and a control circuit. The transmission assembly is used to connect the motor and the drive screw 342, and the control circuit is used to control the rotation of the motor.
[0099] In some embodiments, as shown in Figure 16, the slider assembly 35 also includes a slider member 351, a connecting member 352 and a sliding seat member 353. The sliding seat member 353 is slidingly connected to the guide rod 341 and the driving screw rod 342. The sliding seat member 353 is also connected to the connecting member 352, and the slider member 351 is installed on the connecting member 352.
[0100] In some embodiments, as shown in Figure 17, the connecting member 352 is provided with a cavity, the sliding member 353 is installed in the cavity of the connecting member 352, and the sliding member 353 and the connecting member 352 are both provided with through holes corresponding to the guide rod 341 and the driving screw rod 342. The guide rod 341 and the driving screw rod 342 pass through the through holes of the sliding member 353 and the through holes of the connecting member 352, thereby allowing the slider assembly 35 to move linearly along the first direction or the second direction on the driving assembly 34.
[0101] In some embodiments, as shown in Figure 18, the first clamping assembly 36 includes: a first supporting member 361, a first cover member 362 and a first fixing stud 363, the first supporting member 361 is connected to the first cover member 362, the receiving member 311 of the first injector 31 is installed between the first supporting member 361 and the first cover member 362, and the first fixing stud 363 is used to keep the first supporting member 361 and the first cover member 362 fixed.
[0102] The first supporting member 361 is provided with a plurality of V-shaped mounting grooves, each of which is used to mount a receiving member 311 of the first pourer 31. After the receiving member 311 of the first pourer 31 is placed in the mounting groove, the first cover member 362 is placed on the first pourer 31. This improves the stability between the three parts and reduces shaking.
[0103] Before installing the first syringe 31 on the first clamping assembly 36, first separate the first cover 362 from the first support member 361, then install the container 311 of the first syringe 31 on the first support member 361, and then install the first cover 362 on the first support member 361. The three are then fastened together using the first fixing screws 363. In this way, the syringe can be stably clamped to the first clamping assembly 36.
[0104] The diameter of the upper section of the first fixing stud 363 is larger than the diameter of the lower section. The first cover 362 has a through hole to allow the lower section of the first fixing stud 363 to pass through and engage the upper section of the first threaded stud. The lower section of the first fixing stud 363 and the first supporting member 361 are also provided with interfitting threads and thread grooves to secure the first fixing stud 363 to the first supporting member 361.
[0105] 18 , the first clamping assembly 36 further includes a handle 364 and a first cover 362 . The user can lift the first clamping assembly 36 through the handle 364 .
[0106] As shown in Figure 17, the first supporting member 361 is connected to the slider member 351 via screws. A space is reserved between the first supporting member 361 and the slider member 351 via a positioning pin 38. The first cover member 362 has screw holes to facilitate tightening the screws connecting the first supporting member 361 and the slider member 351.
[0107] In some embodiments, as shown in FIG18 , the first clamping assembly further includes a hook member 365 and a first positioning member 366, and the slider assembly 35 further includes a buckle member 355, which is movably connected to the hook member 365. The upper portion of the slider member 351 is a protrusion, the width of which in the third direction is the same as the distance between the two first positioning members 366 of the first clamping assembly 36. The two first positioning members 366 can mate with the protrusion, and the buckle member 355 is then fastened to the hook member 365 to ensure stability between the first clamping assembly 36 and the slider assembly 35.
[0108] In some embodiments, as shown in FIG19 , the first clamping assembly 36 further includes a first clamping member 367 and a first locking member 368. The first locking member 368 is connected to the first supporting member 361, and the first clamping member 367 is connected to the first locking member 368. The first clamping member 367 is used to secure the container 311 of the first syringe 31 to the first supporting member 361. A protrusion is provided at one end of the container 311 of the first syringe 31. The protrusion is clamped between the first clamping member 367 and the first supporting member 361, thereby further improving the stability between the first syringe 31 and the first clamping assembly 36.
[0109] Illustratively, the first locking member 368 is connected to the first supporting member 361 and is rotatable. The first locking member 368 and the first clamping member 367 are provided with cooperating threads and thread grooves. The first locking member 368 is rotated to adjust the tightness between the first clamping member 367 and the first supporting member 361, thereby adjusting the tightness between the first clamping member 367 and the first supporting member 361, thereby facilitating the removal and placement of the first syringe 31.
[0110] In some embodiments, as shown in Figure 20, the second clamping assembly 37 includes: a second supporting member 371, a second cover member 372 and a second fixing stud 373, the second supporting member 371 is connected to the second cover member 372, and the accommodating member 321 of the second injector 32 is installed between the second supporting member 371 and the second cover member 372.
[0111] The second supporting member 371 is connected to the second cover member 372 , the receiving member 321 of the second injector 32 is installed between the second supporting member 371 and the second cover member 372 , and the second fixing screw 373 is used to keep the second supporting member 371 and the second cover member 372 fixed.
[0112] The second supporting member 371 is provided with a plurality of V-shaped mounting grooves, each of which is used to mount two receiving members 321 of the second pouring device 32. After the receiving members 321 of the second pouring device 32 are placed in the mounting grooves, the second cover member 372 is placed on the second supporting member 371. This improves the stability between the three and reduces shaking.
[0113] Before installing the second syringe 32 on the second clamping assembly 37, first separate the second cover 372 from the second support member 371, then install the container 321 of the second syringe 32 on the second support member 371, and then install the second cover 372 on the second support member 371. The three are then fastened together using the second fixing screws 373. In this way, the syringe can be stably clamped to the second clamping assembly 37.
[0114] The upper section of the second fixing stud 373 has a larger diameter than the lower section. The second cover 372 has a through hole to allow the lower section of the second fixing stud 373 to pass through and engage the upper section of the second threaded stud. The lower section of the second fixing stud 373 and the second supporting member 371 also have mating threads and thread grooves to secure the second fixing stud 373 to the second supporting member 371.
[0115] In some embodiments, the second clamping assembly 37 also includes a second fixing stud 374, the base 33 includes a clamping assembly mounting plate 335, and the second fixing stud 374 is used to fix the second supporting member 371 on the clamping assembly mounting plate 335. As shown in Figure 17, a positioning pin 38 is provided between the second supporting member 371 and the clamping assembly mounting plate 335 to separate the second supporting member 371 and the clamping assembly mounting plate 335.
[0116] In some embodiments, the second cover member 372 is provided with a through hole to facilitate a user to operate the second fixing screw 374 through the through hole.
[0117] In some embodiments, the second clamping assembly 37 further includes a support frame 375 and an indexing pin 376 .
[0118] In some embodiments, as shown in Figure 21, the second clamping assembly 37 also includes: a second clamping member 377 and a second locking member 378, the second locking member 378 is connected to the second supporting member 371, the second clamping member 377 is connected to the second locking member 378, and the second clamping member 377 is used to fix the container 321 of the second injector 32 to the second supporting member 371.
[0119] Exemplarily, the second locking member 378 is rotatably connected to the second supporting member 371. The second locking member 378 and the second clamping member 377 are provided with interlocking threads and thread grooves. The second locking member 378 is rotated to adjust the tightness between the second clamping member 377 and the second supporting member 371, thereby adjusting the tightness between the second clamping member 377 and the second supporting member 371, thereby facilitating the removal and placement of the second syringe 32. The housing 321 of the second syringe 32 has a protrusion at one end. This protrusion is clamped between the second clamping member 377 and the second supporting member 371, further enhancing the stability between the second syringe 32 and the second clamping assembly 37.
[0120] In some embodiments, as shown in FIG. 22 , the second clamping assembly 37 further includes a support frame member 375 and an indexing pin 376 . The support frame member 375 is connected to the second cover member 372 , and the indexing pin 376 is connected to the second cover member 372 .
[0121] In some embodiments, as shown in Figure 22, the first clamping assembly 36 includes: a first positioning member 366, the first positioning member 366 has a positioning hole, the second clamping assembly 37 also includes an indexing pin 376, the indexing pin 376 is matched with the positioning hole, the indexing pin 376 is installed on the support frame, and when the first clamping assembly 36 and the second clamping assembly 37 are combined, the support frame member 375 is used to support the first clamping assembly 36.
[0122] For example, as shown in FIG22 , the first clamping assembly 36 and the second clamping assembly 37 can be stacked together. After the first and second clamping assemblies 36 and 37 are respectively installed on the first and second syringes 31 and 32, they are first stacked together as a whole and then installed on the injection device 100. When stacked, the first clamping assembly 36 is on top and the second clamping assembly 37 is on the bottom. The support frame 375 of the second clamping assembly 37 separates the first and second clamping assemblies 36 and 37 and provides support for the first clamping assembly 36. Indexing pins 376 are mounted on both ends of the support frame member 375. These indexing pins 376 include retractable pins that engage with the positioning holes of the first positioning member 366. When the first clamping assembly 36 and the second clamping assembly 37 are stacked together, the pins extend and engage with the positioning holes to maintain stability between the first clamping assembly 36 and the second clamping assembly 37. When the first clamping assembly 36 and the second clamping assembly 37 need to be separated, the pins retract and withdraw from the positioning holes, allowing the first clamping assembly 36 to be removed from the second clamping assembly 37. After the first clamping assembly 36 and the second clamping assembly 37 are stacked, the second clamping assembly 37 is first secured to the base 33, then removed from the first clamping assembly 36 and mounted on the slider assembly 35. The first clamping assembly 36 and the slider assembly 35 are then secured together using the buckle 355 and the hook 365.
[0123] In some embodiments, as shown in FIG. 22 , the first clamping assembly 36 further includes a hand-held component 364 , which is connected to the first cover component 362 to facilitate the user to lift and place the first clamping assembly 36 .
[0124] The stacking mechanism of the first clamping assembly 36 and the second clamping assembly 37 facilitates the user to simultaneously operate two sets of syringes for respectively realizing the injection function and the withdrawal function, thereby avoiding the mixing or misuse of syringes in a biological reaction.
[0125] In some embodiments, the second clamping assembly 37 further includes a second positioning member. When multiple second clamping assemblies 37 are stacked together, the second positioning member is used to cooperate with the indexing pin 376.
[0126] In some embodiments, as shown in FIG23 , the first fixing member 354 includes a first fixing groove 3541 and a first limiting plate 3542. Referring to FIG17 , the first fixing groove 3541 is provided on one side of the first fixing member 354 proximal to the slider 351, while the first limiting plate 3542 is provided on the other side of the first fixing member 354, with the two sides facing each other. The first fixing groove 3541 is configured to receive the protruding plate of the piston 322 of the second syringe 32. The first limiting plate 3542 defines a channel, for example, V-shaped. The channel of the first limiting plate 3542 is smaller than the protruding plate, thereby clamping the protruding plate of the piston 322 of the second syringe 32, thereby pulling the accommodating member 321 of the second syringe 32 in the first direction. It should be noted that the first limiting plate 3542 and the first fixing member 354 can be integrally formed or separately formed and then combined.
[0127] In some embodiments, as shown in FIG24 , the second fixing member 331 includes a second fixing groove 3311 and a second limiting plate 3312. The second fixing groove 3311 is provided on the side of the second fixing member 331 facing the second direction, and the second limiting plate 3312 is also provided on the side of the second fixing member 331 facing the second direction. The second fixing groove 3311 is configured to receive the protruding plate of the piston 312 of the first syringe 31. The second limiting plate 3312 defines a channel, for example, a V-shaped channel. The channel of the second limiting plate 3312 is smaller than the protruding plate, thereby clamping the protruding plate of the piston 312 of the first syringe 31, thereby preventing the piston 312 of the first syringe 31 from moving in the second direction along with the container 311 of the first syringe 31. It should be noted that the second limiting plate 3312 and the second fixing member 331 can be integrally formed or separately formed and then combined.
[0128] The first fixing member 354 and the second fixing member 331 are used to fix the piston portion of the second filling member and the piston portion of the first filling member, respectively. In this way, it can be ensured that during the movement of the container 311 of the first pourer 31 and the piston portion 322 of the second pourer 32, the piston portion of the first pourer 31 and the piston portion of the second pourer 32 are always fixed, thereby ensuring the movement accuracy of the piston member 312 of the first pourer 31 in the container 311 of the first pourer 31 and the movement accuracy of the piston member 322 of the second pourer 32 in the container 321 of the second pourer 32, thereby improving the fluid replacement accuracy.
[0129] In some embodiments, as shown in FIG25 , the fixture 100 further includes a tray handle 15 and a support plate 16. The tray handle 15 and the support plate 16 are both mounted on the tray 14. The support plate 16 is provided with a plurality of slots, each of which is used to stabilize a connecting tube 41.
[0130] In some embodiments, as shown in FIG26 , bioreactor system 400 further includes a first containment cabinet 42 and a second containment cabinet 43. The first containment cabinet is used to house perfusion device 300, and the second containment cabinet 43 is used to house fixture 100, wherein fixture 100 holds microfluidic chip 200, as shown in FIG2 . First containment cabinet 42 and second containment cabinet 43 have functions such as temperature and humidity control, dust prevention, and illumination, thereby providing a favorable reaction environment for the bioreactor.
[0131] In some embodiments, as shown in FIG. 26 , the first storage cabinet 42 further includes a cable tie 421 , which is used to bundle the connecting tubes 41 to prevent the connecting tubes 41 from being scattered and disordered.
[0132] In some embodiments, as shown in FIG26 , the second storage cabinet 43 further includes: a partition groove 431 and a support plate 432. The partition grooves 431 are respectively provided on two opposite side walls of the storage cavity of the second storage cabinet 43. Every two corresponding partition grooves 431 are used to accommodate the support plates 432. The support plates 432 are used to place the fixture 100.
[0133] In some embodiments, a light source may be placed on the carrier plate 432 placed above the fixture 100 . The light source is used to provide necessary lighting conditions for the microfluidic chip 200 in the fixture 100 to complete the biological reaction.
[0134] The carrier plate 432 can be made of a transparent material, such as glass and acrylic plate, so that an observation device can be placed on the carrier plate 432 below the fixture 100 to observe the microfluidic chip 200 in the fixture 100 through the carrier plate 432 on which the fixture 100 is placed.
[0135] In some embodiments, as shown in FIG27 , a bottom opening 34 is provided at the bottom of the microfluidic chip 300 , and the bottom opening 34 is connected to the cavity 32 shown in FIG2 . The bottom opening 34 is used to observe the biological reaction process in the cavity 32 .
[0136] In some embodiments, as shown in the tray 14 of FIG. 7 , the area at the bottom of the receiving tank of the tray 14 corresponding to the bottom opening 34 shown in FIG. 27 is made of a transparent material to facilitate observation of the microfluidic chip 200 in the fixture 100 through the area.
[0137] In some embodiments, as shown in FIG28 , the first opening 3311 of the micropore 331 of the capillary tube 33 is larger than the second opening 3312 of the micropore 331. The first opening 3311 corresponds to the opening of the micropore 331 on the outside of the capillary tube 33, while the second opening 3312 corresponds to the opening of the micropore on the inside of the capillary tube. The first opening 3311 gradually decreases toward the second opening 3312. When machining the wall of the micropore 331, process deviations may result in insufficient opening size of the micropore 331. Through the above-described opening mechanism, the micropore 331 is gradually reduced from the outside to the inside when it is formed on the capillary tube 33, ensuring the accuracy of the second opening 3312.
[0138] In some embodiments, the minimum width of the second opening 3312 ranges from 1 μm to 20 μm. Specifically, the minimum width of the second opening 3312 ranges from 3 μm. The minimum width of the second opening 3312 ranges from the width of the narrowest point of the second opening 3312. For example, if the second opening 3312 is rectangular, the wide side of the rectangle is the narrowest point of the second opening 3312, and the length of the wide side of the rectangle is the minimum width of the second opening 3312. The second opening 3312 facilitates the slow outflow of nutrients from the liquid in the cavity 32 as shown in FIG. 2, creating a capillary-like culture environment for better culturing biological cells.
[0139] In some embodiments, in order to improve production efficiency and precision, the microfluidic chip is integrally formed by photocuring 3D printing.
[0140] In a hardware implementation, the division between the functional modules / units mentioned in the above description does not necessarily correspond to the division of physical modules; for example, a physical module may have multiple functions, or a function or step may be performed by several physical modules in cooperation. Some physical modules or all physical modules may be implemented as software executed by a processor, such as a central processing unit, a digital signal characteristic electrical signal processor or a microprocessor, or implemented as hardware, or implemented as an integrated circuit, such as an application-specific integrated circuit. Such software may be distributed on a computer-readable medium, which may include a computer storage medium (or non-transitory medium) and a communication medium (or temporary medium). As known to those of ordinary skill in the art, the term computer storage medium includes volatile and non-volatile, removable and non-removable media implemented in any method or technology for storing information (such as computer-readable instructions, data structures, program modules or other data). Computer storage media include, but are not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disk (DVD) or other optical disk storage, magnetic cassettes, magnetic tapes, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store desired information and can be accessed by a computer. Furthermore, as is well known to those skilled in the art, communication media typically embodies computer-readable instructions, data structures, program modules, or other data in a modulated data signal such as a carrier wave or other transport mechanism, and may include any information delivery media.
[0141] The preferred embodiments of the present application are described above with reference to the accompanying drawings, but are not intended to limit the scope of the present application. Any modifications, equivalent substitutions, and improvements made by those skilled in the art without departing from the scope and essence of the present application shall fall within the scope of the present application.
Claims
1. A biological reaction system, the biological reaction system comprising: A microfluidic chip; A fixture, the fixture comprising: a fixture body and a fixing component, a receiving groove being formed on a first surface of the fixture body, a second surface of the fixture body being opposite to the first surface, the receiving groove being for placing the microfluidic chip, the fixture body further being provided with a liquid injection flow channel and a liquid extraction flow channel, a first end of the liquid injection flow channel being for delivering liquid to the microfluidic chip, the liquid discharged from the microfluidic chip flowing into the receiving groove, the receiving groove being in communication with a first end of the liquid extraction flow channel; the fixing component being disposed on the fixture body for fixing the microfluidic chip in the receiving groove; An infusion device, the infusion device being respectively connected to a second end of the liquid injection flow channel and a second end of the liquid extraction flow channel for performing liquid replacement on the microfluidic chip.
2. The biological reaction system according to claim 1, wherein, The microfluidic chip comprises: A chip body; A cavity, an opening of the cavity being located on a second surface of the chip body, the second surface and a first surface of the chip body being opposite; A capillary, the capillary being located in the cavity; Wherein, a liquid inlet and a liquid outlet are further formed on a third surface of the chip body, the capillary being capable of performing liquid replacement through the liquid inlet and the liquid outlet, the third surface of the chip body being perpendicular to the first surface and the second surface of the chip body.
3. The biological reaction system according to claim 2, wherein, The capillary is provided with at least one micropore, a first opening of the micropore being larger than a second opening of the micropore, the first opening being an opening corresponding to the outside of the capillary of the micropore, the second opening being an opening corresponding to the inside of the capillary of the micropore, the first opening gradually narrowing towards the second opening.
4. The fixture of the microfluidic chip according to claim 1, wherein, A communication groove is further formed on the first surface of the fixture body, and the liquid flowing out of the microfluidic chip flows into the receiving groove through the communication groove.
5. The fixture of the microfluidic chip according to claim 1, wherein, An observation through-hole is further formed between the first surface and the second surface of the fixture body, the observation through-hole being in communication with the receiving groove.
6. The fixture of the microfluidic chip according to claim 1, wherein, An anti-overflow groove is further formed on the first surface of the fixture body, the anti-overflow groove being connected to a second end of the liquid extraction flow channel, the anti-overflow groove and the receiving groove being in a stepped shape.
7. The fixture of the microfluidic chip according to claim 1, wherein, A height difference between the anti-overflow groove and the receiving groove is: 0.5 mm - 3 mm; and / or, a distance between a side wall of the anti-overflow groove and a second end of the liquid extraction flow channel is: 2 mm - 5 mm.
8. The fixture of the microfluidic chip according to claim 1, wherein, A first connection component is disposed on the second surface of the fixture body, the fixture further comprising a fixture cover, the fixture cover comprising: A second connection component for connecting with a first connection component of the fixture body; Two guiding holes, the guiding holes communicating a second surface and a first surface of the fixture cover, the second surface and the first surface of the fixture cover being opposite, the two guiding holes respectively corresponding to a first end of the liquid injection flow channel and a first end of the liquid extraction flow channel.
9. The biological reaction system according to any one of claims 1-8, wherein, The perfusion device comprises: A base; A driving component, the driving component being disposed on the base; A slider component, the slider component being slidably connected to the driving component, the driving component being for driving the slider component to move; The first clamping assembly is mounted on the slider assembly and is used to fix the housing of at least one first injector. The second clamping assembly is mounted on the base and is used to fix the housing of at least one second injector. Wherein, the slider assembly includes a first fixing member for fixing the piston member of the second injector, and / or the base is provided with a second fixing member for fixing the piston member of the first injector; the driving assembly drives the slider assembly to move, driving one of the first injector and the second injector to perform a liquid suction function and the other to perform a liquid injection function.
10. The biological reaction system according to claim 9, wherein, The driving assembly includes: a motor, a guide rod and a driving lead screw. The base includes a main seat, a first support and a second support. The first support and the second support are oppositely arranged on the main seat. The two ends of the guide rod and the driving lead screw are respectively mounted on the first support and the second support. The motor is arranged on any one of the main seat, the first support and the second support. The motor is used to drive the driving lead screw to rotate. The driving lead screw is also connected to the slider assembly and is thus used to drive the slider assembly to move. The slider assembly further includes a slider member, a connecting member and a sliding seat member. The sliding seat member is slidably connected to the guide rod and the driving lead screw. The sliding seat member is also connected to the connecting member. The slider member is mounted on the connecting member.
11. The biological reaction system according to claim 9, wherein, The first clamping assembly includes: a first supporting member and a first cover member. The first supporting member is connected to the first cover member. The housing of the first injector is mounted between the first supporting member and the first cover member. The second clamping assembly includes: a second supporting member and a second cover member. The second supporting member is connected to the second cover member. The housing of the second injector is mounted between the second supporting member and the second cover member.
12. The biological reaction system according to any one of claims 1-8, wherein, The fixture further includes a tray for placing the fixture body.
13. The biological reaction system according to any one of claims 1-8, wherein, The microfluidic chip is integrally formed by light-curing 3D printing.
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