CN114247488A - Manufacturing method of bag reactor - Google Patents
Manufacturing method of bag reactor Download PDFInfo
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- CN114247488A CN114247488A CN202111391282.9A CN202111391282A CN114247488A CN 114247488 A CN114247488 A CN 114247488A CN 202111391282 A CN202111391282 A CN 202111391282A CN 114247488 A CN114247488 A CN 114247488A
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 22
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 95
- 239000010408 film Substances 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 32
- 238000007731 hot pressing Methods 0.000 claims abstract description 23
- 239000010409 thin film Substances 0.000 claims abstract description 21
- 239000012528 membrane Substances 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 85
- 238000001514 detection method Methods 0.000 claims description 29
- 238000002493 microarray Methods 0.000 claims description 27
- 239000000463 material Substances 0.000 claims description 8
- 238000007789 sealing Methods 0.000 claims description 8
- 239000002994 raw material Substances 0.000 claims description 5
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- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
Abstract
The present invention relates to a method of manufacturing a bag reactor comprising at least one set of reagent tubing sets, the ends of the set of reagent tubing sets comprising outwardly extending side edges; the method comprises the following steps: bonding a first thin film on a side surface of the side of the end of the reagent tube group by first hot pressing; inverting the first film a first time such that the first film extends in a direction along the side of the end of the set of reagent tubes; inverting the set of reagent tubes and the first membrane a second time; and bonding a second thin film to the first thin film and the tip of the set of reagent tubes by a second hot press. The manufacturing method of the bag reactor is low in production difficulty and high in yield, and can greatly improve the use and popularization of the bag reactor.
Description
Technical Field
The invention relates to the technical field of biological detection, in particular to a manufacturing method of a bag reactor.
Background
The micro-fluidic chip is based on micro-electro-mechanical systems (MEMS), structures such as a cavity, a pipeline, a valve and the like are constructed on a chip substrate made of a certain material, and a fluid driving strategy is adopted to drive fluid to complete biological reaction among the structures of the chip.
At present, in the chip design process, functional modules are generally designed according to reaction types in the industry, then structural layered mold-opening injection molding processing is carried out, most of materials are plastic materials such as PMMA, PDMS, PC, PP and the like, and proper lyophilic-lyophobic and biocompatible treatment is carried out on reaction fluid passing positions. In the chip design and processing process, structural units such as cavities, pipelines and valves are constructed, and meanwhile, the function realization, the biological reaction compatibility and the mass production economy are considered. The chip processing mode based on mold opening injection generally puts restrictions on the design of the structural units, such as the preset inlet of the reagent in the cavity, the stereo cross design of the pipeline, the structure of the valve, and the like, and the pretreatment of hydrophilic and hydrophobic treatment is also inconvenient for the chip structural units with more layers.
The common fluid driving strategies in chip design at present are: 1. in the variable speed centrifugal type, fluid is driven to an outer ring cavity from an inner ring reaction cavity layer by layer, which is mostly seen in the design of a disc type chip; 2. the vacuum negative pressure type is characterized in that a rigid reaction chamber is used for presetting a vacuum environment, and liquid is automatically sucked; 3. the air pump is driven by external force, an air receiving port is reserved on the chip, and the air pump is used for inflating the air body to suck air so as to drive the fluid to move among the reaction units. In the aspect of chip fluid drive, a variable-speed centrifugal type generally needs to place a chip on a high-speed rotating device, the reaction on the chip needs to have conditions such as temperature rise and temperature reduction and the like on some occasions, and the rotating device can seriously restrict the realization of a variable-temperature function, so that a centrifugal-based disc type chip is commonly used in the field of constant-temperature reaction; the vacuum negative pressure type driving adopts a rigid pre-vacuum chamber, fluid can be automatically sucked, but the suction process is generally irreversible; the air pump rule adopts the operation of aerifing and breathing in to drive fluid motion, and external valve interface is comparatively complicated, and drives the effect controllability poor.
The prior art includes an integrated microfluidic chip. The microfluidic chip consists of a reagent storage tube group, a flexible bag reaction chamber, a pipeline module and a reaction detection module, wherein all the modules are mutually communicated through pipelines; the reagent storage tube group consists of a reagent tube and a matched push rod, and reagents required by reaction are preset in the reagent storage tube group. The flexible bag module comprises an upper layer of hot-press bonded plastic film material and a lower layer of hot-press bonded plastic film material, wherein an unbonded area forms a reaction chamber and a pipeline, and fluid in the chip can be driven by external extrusion, so that the chip has the characteristics of low preparation and use cost and the like, and can be universally used in the fields of immunodetection, molecular diagnosis and the like.
Disclosure of Invention
In view of the technical problems in the prior art, the present invention provides a method for manufacturing a bag reactor, the bag reactor comprising at least one set of reagent tube sets, the ends of the set of reagent tubes comprising outwardly extending side edges; the method comprises the following steps: bonding a first thin film on a side surface of the side of the end of the reagent tube group by first hot pressing; inverting the first film a first time such that the first film extends in a direction along the side of the end of the set of reagent tubes; inverting the set of reagent tubes and the first membrane a second time; and bonding a second thin film to the first thin film and the tip of the set of reagent tubes by a second hot press.
The method as described above, wherein the second hot-pressed mold comprises one or more patterns, and the first film and the second film are not hot-pressed and bonded together in the areas defined by the one or more patterns.
The method as above, wherein the one or more patterns define one or more reaction chambers, the method further comprising placing one or more reaction raw materials into the one or more reaction chambers after the second hot pressing; and then sealing the one or more reaction chambers by third hot pressing, wherein the reaction raw materials are grinding materials, magnetic beads or reagents.
The method as described above, further comprising perforating the first film to define an area of a microarray reaction detection module prior to the second hot pressing, wherein only the second film is included in the area of the microarray reaction detection module after the second hot pressing.
The method as described above, further comprising bonding a microarray reaction detection module to the region of the microarray reaction detection module and enclosing the region.
The method as described above, further comprising evacuating the bag reactor using an interface on the set of reagent tubes.
The method of the above, further comprising, prior to the evacuating, positioning a plunger of the set of reagent tubes in a first positioning position, wherein a position of the plunger is fixed in the first positioning position.
The method of the above, further comprising, after the evacuating, positioning a pusher of the set of reagent tubes in a second positioning position, wherein in the second positioning position the pusher is movable in the set of reagent tubes.
The method as described above, wherein the width of the side is 1-3 mm.
The method as described above, wherein the second hot pressing is performed by hot-pressing and bonding a male mold and a female mold, wherein the male mold has a higher temperature to bond the first thin film and the second thin film, and the female mold has a lower temperature to bond the first thin film and the second thin film, so as to form one or more reaction chambers and conduits.
The method as described above, wherein the bottom of each reagent tube in the reagent tube set is provided with a small hole, and the small hole is connected with the buffer solution inlet or the sample inlet through a bottom pipeline respectively.
The method as described above, wherein the small holes at the bottom of each reagent tube in the reagent tube set are connected with the one or more reaction chambers and the microarray reaction detection module through the pipelines to realize nucleic acid reaction and result detection.
The manufacturing method of the bag reactor is low in production difficulty and high in yield, and can greatly improve the use and popularization of the bag reactor.
Drawings
Preferred embodiments of the present invention will now be described in further detail with reference to the accompanying drawings, in which:
FIG. 1 is a schematic view of a bag reactor according to one embodiment of the present application;
FIG. 2 is a flow chart of a method of manufacturing a bag reactor according to one embodiment of the present application; and
fig. 3A-3D are flow diagrams of a bag reactor manufacturing process according to one embodiment of the present application.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the following detailed description, reference is made to the accompanying drawings that form a part hereof and in which is shown by way of illustration specific embodiments of the application. In the drawings, like numerals describe substantially similar components throughout the different views. Various specific embodiments of the present application are described in sufficient detail below to enable those skilled in the art to practice the teachings of the present application. It is to be understood that other embodiments may be utilized and structural, logical or electrical changes may be made to the embodiments of the present application.
FIG. 1 is a schematic view of a bag reactor according to one embodiment of the present application. As shown, the bag reactor 100 includes at least one set of reagent tube sets 110, one or more reaction chambers 120, and a microarray reaction detection module 130. Wherein the set of reagent tubes 110 can be used to push reagents into the reaction chamber and/or the microarray reaction detection module; the reaction chamber 120 may provide a chamber required for a reaction; the microarray reaction detection module 130 may be used to detect the results of the reaction; the reagent tube set 110, the reaction chamber 120 and the microarray reaction and detection module 130 can be connected by a connecting pipeline 140 to realize fluid driving and transferring in the bag reactor. In some embodiments, the reagent tube set may be injection molded. In some embodiments, the reaction chamber may be fabricated directly on the set of reagent tubes. In some embodiments, the microarray reaction detection module may be directly connected to the reaction chamber or the set of reagent tubes.
The method of manufacturing the bag reactor of the present application will be described in detail below.
FIG. 2 is a flow chart of a method of manufacturing a bag reactor according to one embodiment of the present application. Fig. 3A-3D are flow diagrams of a bag reactor manufacturing process according to one embodiment of the present application.
In step 210, a first film is bonded to the side of the end of the set of reagent tubes by hot pressing. Referring to fig. 3A, the bag reactor 100 may comprise at least one set of reagent tubing 110, the ends of which comprise outwardly extending sides 101. Side 101 includes a side 109. In the manufacturing method of the present application, the side 109 of the side 101 is selected to provide a basis for thermocompression bonding the first thin film 121, thereby thermocompression bonding the first thin film 121 and the side 101 of the reagent tube set together. For example, the first film 121 is arranged in a horizontal direction, the reagent tube set 110 is provided entirely horizontally below the first film 121, and the side surface 109 of the side 101 of the reagent tube set 110 faces upward. The first film 121 is thermocompression bonded directly to the side 109 of the side 101 by a thermocompressor. In some embodiments, the width of the side 109 may be 1-3mm to facilitate better thermocompression bonding of the first film to the sides of the set of reagent tubes, providing sufficient strength. Sufficient sealability between the first film 121 and the side edge 101 can be ensured even after the subsequent evacuation step.
In step 220, the first membrane 121 is inverted so that it extends in the direction of the side of the end of the set of reagent tubes. Referring to fig. 3B, when the first film 121 is thermocompression bonded to the side edge, the first film 121 is located in a plane perpendicular to the extending direction of the side edge 101. The first film 121 may be further extended by turning the first film 121 over (e.g. 90 degrees) such that the first film 121 extends substantially along the direction in which the side edge 101 extends, such that the first film 121 is substantially in the same plane as the ends of the set of reagent tubes. The first membrane 121 is inverted so that its position relative to the set of reagent tubes 110 is approximately that of the final product. The difficulty of manufacturing the bag reactor is simplified through the steps 210 and 220, and the end of the reagent tube set 110 can be prevented from being blocked, thereby improving the yield of products.
In step 230, the reagent tube set 110 and the first membrane 121 are inverted as a whole. Referring to fig. 3B, by integrally inverting the ends of the reagent tube sets and the first film 121 in the same plane, a basis for a subsequent fabrication process can be provided. For example: the reagent tube set 110 and the first film 121 may be turned over by 90 degrees so that the whole of the reagent tube set 110 and the first film 121 face in a vertical direction for facilitating the subsequent hot pressing of the second film 122.
In step 240, referring to fig. 3B, the second thin film 122 is bonded to the first thin film 121 and the end of the reagent tube set 110 by thermocompression, thereby completing the fabrication of the reaction chamber 120 and connecting the reaction chamber 120 to the reagent tube set 110. In some embodiments, the hot-pressed mold may include one or more patterns, and the first film and the second film are not hot-pressed bonded together in one or more pattern-defined areas, such that the one or more pattern-defined areas form one or more reaction chambers 120.
For example: the hot pressing of the second film 122 may be performed by hot press bonding using a male mold, wherein the male mold has a higher temperature to bond the first film 121 and the second film 122, and the female mold has a lower temperature to bond the first film 121 and the second film 122, such that the female mold is positioned to define one or more reaction chambers 120. The respective reaction chambers and other structures and the connecting pipes 140 therebetween can be formed by the same method.
In some embodiments, the reagent tube set 110 may comprise at least 2 reagent tubes 102, a sample inlet 103, and a buffer inlet 104. The reagent tube 102 may be connected to different reaction chambers 120, or connected to the reaction chamber 120 and the microarray reaction and detection module 130, respectively; the sample inlet 103 and the buffer inlet 104 may respectively communicate with a portion of the reagent tube 101, so that the sample and/or the buffer may be pushed into the reaction chamber 120 and/or the microarray reaction detection module 130 by using the reagent tube. In some embodiments, the sample inlet 102 is connected to only one of the reagent tubes in the reagent tube set, and the remaining other reagent tubes in the reagent tube set are connected to the buffer inlet.
In some embodiments, the bottom of each of the reagent tubes in the reagent tube set is provided with a small hole 105, and the small hole 105 can be connected to the buffer inlet 104 or the sample inlet 103 through a groove on the first end of the reagent tube set. In some embodiments, the small holes 105 at the bottom of each reagent tube in the reagent tube set can also be connected with the reaction chamber 120 and/or the microarray reaction detection module 130 to realize the relevant reaction and result detection. In some embodiments, the wells 105 can be connected to the reaction chamber 120 and/or the microarray reaction detection module 130 via tubing 140 (or a groove on the first end of the set of binding reagent tubes) to allow for biological reactions and detection of results.
Referring to fig. 3C, in some embodiments, prior to hot pressing the second film 122, the first film 121 may be perforated, for example: an opening 131 is formed in the first film 121 to define a region of the microarray reaction detecting module 130. And after hot-pressing the second film 122, only the second film 122 may be included in an area defining the microarray reaction detecting module 130. In some embodiments, the first film may be perforated before the first film and the reagent tube set are integrally inverted, or before the first film is inverted or before the first film is hot-pressed on the side of the reagent tube set. In some embodiments, the microarray reaction detecting module 130 may be further bonded to a defined region and the region may be sealed, and the microarray reaction detecting module 130 may be connected to the reagent tube set 110 and/or the reaction chamber 120.
Referring to fig. 3D, in some embodiments, one or more pattern-defined areas may also not be enclosed when the second film 122 is hot-pressed. In other words, that is, one or more reaction chambers 120 are not closed, after hot-pressing the second film, one or more reaction raw materials may be put into one or more reaction chambers, and then one or more reaction chambers 120 may be closed by hot-pressing again. In some embodiments, the reaction material may be an abrasive, magnetic beads, or reagents, among others.
Referring to fig. 3D, in some embodiments, the reagent tube set may further include an interface 106 thereon, which may be used to evacuate the reaction chambers and/or microarray reaction detection modules attached to the reagent tube set 110 and the reagent tube set. Evacuating the bag reactor using the interface on the set of reagent tubes is also a step in the manufacture of the bag reactor. For example: after bonding the microarray reaction detection module, the whole bag reactor is sealed integrally, and the reaction chamber and/or the microarray reaction detection module can be vacuumized through the interface on the reagent tube group.
In some embodiments, the push rod 107 of the reagent tube set may be placed in the first position prior to evacuating the bag reactor, and the push rod 107 is fixed in the first position to avoid affecting the evacuation of the bag reactor. In some embodiments, after evacuation of the bag reactor, the push rod of the reagent tubing set may be placed in a second position in which the push rod may close the reagent tubing set from breaking the vacuum environment within the bag reactor. In some embodiments, the pusher bar is movable in the set of reagent tubes in the second positioning position when the bag reactor is performing the relevant reaction.
In some embodiments, the reagent tube set 110 may further comprise a sealing means 108, which may be used to seal the sample inlet 103 as well as the buffer inlet 104. In some embodiments, the sealing device 108 may be a sealing cap that may be removed to allow access to either the sample or the buffer. In some embodiments, the sealing device may also be other structures, such as: and (3) hot-pressing the film, wherein the film is hot-pressed to the sample inlet or the buffer solution inlet to realize sealing, and the film can be punctured to allow a sample or a buffer solution to enter. Referring to fig. 3D, in some embodiments, the sealing device 108 is disposed on the sample inlet and the buffer inlet before the vacuum is applied.
This application bag reactor can accomplish the preparation of reaction chamber through hot pressing film on reagent nest of tubes to bonding microarray reaction detection module can accomplish the connection between each structure of bag reactor on the film, accomplishes bag reactor's preparation, and the production degree of difficulty is low, and the yield is high, improvement its use and popularization that can be great.
The above embodiments are provided only for illustrating the present invention and not for limiting the present invention, and those skilled in the art can make various changes and modifications without departing from the scope of the present invention, and therefore, all equivalent technical solutions should fall within the scope of the present invention.
Claims (12)
1. A method of manufacturing a bag reactor comprising at least one set of reagent tubing sets, the ends of the set of reagent tubing comprising outwardly extending side edges; the method comprises the following steps:
bonding a first thin film on a side surface of the side of the end of the reagent tube group by first hot pressing;
inverting the first film a first time such that the first film extends in a direction along the side of the end of the set of reagent tubes;
inverting the set of reagent tubes and the first membrane a second time; and
a second thin film is bonded to the first thin film and the distal end of the set of reagent tubes by a second hot press.
2. The method of claim 1, wherein the second heated press mold comprises one or more patterns, the first film and the second film not being heated pressed together in areas defined by the one or more patterns.
3. The method of claim 2, wherein the one or more patterns define one or more reaction chambers, the method further comprising placing one or more reaction raw materials into the one or more reaction chambers after the second hot pressing; and then sealing the one or more reaction chambers by third hot pressing, wherein the reaction raw materials are grinding materials, magnetic beads or reagents.
4. The method of claim 1, further comprising perforating the first film to define an area of a microarray reaction detection module prior to the second hot pressing, wherein only the second film is included in the area of the microarray reaction detection module after the second hot pressing.
5. The method of claim 4, further comprising bonding a microarray reaction detection module to the region of the microarray reaction detection module and enclosing the region.
6. The method of claim 1, further comprising evacuating the bag reactor with an interface on the set of reagent tubes.
7. The method of claim 6, further comprising, prior to the evacuating, positioning a plunger of the set of reagent tubes in a first positioning position, wherein a position of the plunger is fixed in the first positioning position.
8. The method of claim 7, further comprising, after the evacuating, disposing a pusher of the set of reagent tubes in a second positioning position, wherein the pusher is movable in the set of reagent tubes in the second positioning position.
9. The method of claim 1, wherein the width of the side is 1-3 mm.
10. The method of claim 1, wherein the second hot pressing is a male-female film hot press bonding, wherein a higher temperature at the male mold bonds the first thin film to the second thin film, and a lower temperature at the female mold does not bond the first thin film to the second thin film, forming one or more reaction chambers and channels.
11. The method of claim 10, wherein the bottom of each reagent tube in the reagent tube set is provided with a small hole, and the small hole is connected with the buffer solution inlet or the sample inlet through a bottom pipeline.
12. The method of claim 11, wherein the wells at the bottom of each reagent tube in the set of reagent tubes are connected to the one or more reaction chambers and microarray reaction detection module by the tubing to achieve biological reactions and result detection.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111391282.9A CN114247488B (en) | 2021-11-23 | 2021-11-23 | Manufacturing method of bag reactor |
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| CN202111391282.9A CN114247488B (en) | 2021-11-23 | 2021-11-23 | Manufacturing method of bag reactor |
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| CN105197881A (en) * | 2015-08-28 | 2015-12-30 | 中国科学院半导体研究所 | Method for realizing silicon-silicon bonding by using diffusion and mutual dissolution of metal material |
| CN107971052A (en) * | 2018-01-16 | 2018-05-01 | 广东工业大学 | A kind of micro-fluidic chip based on photosensitive dry film and preparation method thereof |
| CN108470812A (en) * | 2018-06-04 | 2018-08-31 | 佛山市国星半导体技术有限公司 | A kind of film flip LED chips and preparation method thereof |
| CN110339879A (en) * | 2019-07-10 | 2019-10-18 | 深圳金迈隆电子技术有限公司 | A kind of manufacturing method on piece laboratory |
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