Method of making a cpg filter element

Abstract

This application discloses a method for manufacturing a CPG filter element, comprising: processing a CPG composite filter element, the CPG composite filter element comprising a core block and a CPG matrix integrally formed on the outside of the core block, the core block being resistant to the environment of the oligonucleotide synthesis process and at least partially exposed; and laser marking the exposed portion of the core block to form unique identification information for the CPG composite filter element. In subsequent oligonucleotide solid-phase synthesis operations, the CPG composite filter element of this application can be tracked based on the unique identification information on the core block, and traceability of the synthesis based on the CPG composite filter element can also be achieved. Furthermore, the embodiments of this application avoid the problems of easy detachment, corrosion, or blurring of markings due to traditional marking methods, leading to information loss, and also avoid the destruction of the integrity of the unique identification information during the high-temperature sintering process of the CPG filter element or the destruction of the pore structure of the CPG filter element by high-energy lasers.

Description

Technical Field

[0001] This application relates to the field of CPG filter technology, and more particularly to a method for manufacturing a CPG filter. Background Technology

[0002] CPG (controllable pore size glass) filters are the core carriers for the solid-phase synthesis of oligonucleotides. In the iterative base synthesis process, multiple synthesis steps based on CPG filters are required, which places high demands on the physical structural stability and information traceability of CPG filters.

[0003] Currently, there is no precedent for coding CPG filter cartridges, making it difficult to track and trace their usage. Furthermore, even if CPG filter cartridges are labeled, traditional methods (such as surface inkjet printing or labeling) are prone to detachment, corrosion, or illegibility under the high-pressure environment of repeated washing with strong acids, strong alkalis, and organic solvents involved in oligonucleotide synthesis, as well as physical abrasion, leading to information loss. If the coding carrier is applied before CPG filter cartridge molding, the high-temperature sintering process may destroy the integrity of the coded information. If the CPG functional areas are directly coded after molding, high-energy lasers may damage the pore structure of the CPG, affecting synthesis performance. Summary of the Invention

[0004] This application provides a method for manufacturing CPG filter elements, which can solve the technical problem that CPG filter elements lack unique identifiers, are easily confused after multiple rounds of synthesis, and lead to incorrect recording of synthesis sequences.

[0005] In view of the above, firstly, embodiments of this application provide a method for manufacturing a CPG filter element, comprising: A CPG composite filter element is manufactured, comprising a core block and a CPG matrix integrally formed on the outside of the core block, wherein the core block is resistant to the environment of the oligonucleotide synthesis process and is at least partially exposed to the outside; Laser marking is performed on the exposed portion of the core block to form unique identification information for the CPG composite filter element.

[0006] Optionally, the environment during the oligonucleotide synthesis process includes a strong acid environment, a strong base environment, and an organic solvent environment.

[0007] Optionally, the core block is made of an inert polymer material.

[0008] Optionally, the inert polymer material is polypropylene, ultra-high molecular weight polyethylene, or high-density polyethylene.

[0009] Optionally, the process of producing the CPG composite filter element includes: The core block is processed; The core block is placed in a predetermined position within the cavity of the mold; A mixture of CPG particles and adhesive particles is filled into the cavity around the core block; The mold after filling is sintered to firmly bond the CPG particles to each other and the CPG particles to the core block with adhesive, forming the CPG composite filter element. The material of the core block is the same as or compatible with the material of the adhesive particles.

[0010] Optionally, the core is completely surrounded laterally by the CPG matrix.

[0011] Optionally, the core block is located at the center of the CPG composite filter element.

[0012] Optionally, the chip has a first end face that is exposed to the outside. The first end face is flush with or recessed relative to the corresponding end face of the CPG substrate. The unique identification information is formed by laser marking on the first end face.

[0013] Optionally, the core has a second end face opposite to the first end face, the second end face being exposed, and laser marking is performed on the second end face to form the unique identification information.

[0014] Optionally, the unique identification information is a QR code, a micro-character array, or a light and dark code.

[0015] In this embodiment, the processed CPG filter element is a CPG composite filter element, comprising a core block and a CPG matrix integrally formed on the outside of the core block. The core block is resistant to the environment of the oligonucleotide synthesis process and is at least partially exposed. The exposed part of the core block is laser-marked to form unique identification information for the CPG composite filter element. Therefore, in the subsequent oligonucleotide solid-phase synthesis process, the presence of the CPG matrix does not affect reagent permeability, and the CPG composite filter element can be tracked based on the unique identification information on the core block, enabling traceability of the synthesis based on the CPG composite filter element. Furthermore, this embodiment avoids the problems of easy detachment, corrosion, or blurring of markings caused by traditional marking methods, leading to information loss. It also avoids the destruction of the integrity of the unique identification information by high-temperature sintering or the damage to the pore structure of the CPG composite filter element by high-energy lasers. Attached Figure Description

[0016] Figure 1 This is a schematic flowchart of the CPG filter element manufacturing method according to an embodiment of this application.

[0017] Figure 2 This is a three-dimensional structural diagram of the CPG composite filter element according to an embodiment of this application.

[0018] Figure 3 This is a three-dimensional structural schematic diagram of the CPG composite filter element from another perspective of the embodiments of this application. Detailed Implementation

[0019] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0020] Please see Figure 1 and Figure 2 This application discloses a method for manufacturing a CPG filter element, comprising: S1, CPG composite filter element 1 is processed. CPG composite filter element 1 includes a core block 10 and a CPG matrix 20 integrally formed on the outside of the core block 10. The core block 10 is resistant to the environment of the oligonucleotide synthesis process and is at least partially exposed to the outside.

[0021] In some embodiments, before processing the CPG composite filter element 1, a core block 10 is first processed, and then a CPG substrate 20 is integrally formed on the outside of the core block 10, thereby forming the CPG composite filter element 1.

[0022] In some embodiments, the CPG composite filter element 1 is manufactured, including: Place the core block 10 in the preset position within the cavity of the mold (not shown); The mixture of CPG particles and adhesive particles is filled around the core block 10 in the cavity; The filled mold is sintered to firmly bond the CPG particles to each other and to the core block 10 with an adhesive (the adhesive particles melt to form a binder for bonding), thus forming the CPG composite filter element 1.

[0023] Specifically, a positioning protrusion can be provided inside the mold to position the core block 10.

[0024] Specifically, the filled mold is placed in a sintering furnace for sintering.

[0025] Specifically, the sintering temperature is 160℃-190℃, the holding time is 1.5h-3h, the heating rate is 2-5℃ / min, and the cooling rate is ≤3℃ / min.

[0026] Specifically, the pore size of the CPG particles is 500Å-1000Å, and the mass ratio of CPG functional particles to binder particles is 6:4-8:2.

[0027] Specifically, the adhesive particles are made of ultra-high molecular weight polyethylene or high-density polyethylene.

[0028] For example, 500 Å CPG particles (150 mesh) are mixed with adhesive particles of ultra-high molecular weight polyethylene material at a mass ratio of 7:3, and then the mixed powder is filled into a mold and compacted by vibration.

[0029] Then, the mold is closed and placed in a vacuum sintering furnace, heated to 180°C at 3°C / min and held for 2.5 hours to melt the adhesive particles and bond the CPG particles into a porous matrix. Simultaneously, the polypropylene core block 10 is tightly bonded to the surrounding matrix. The temperature is then slowly lowered to room temperature at 2°C / min, and after demolding, a φ5mm×3mm embedded composite filter element is obtained. At this point, the two end faces of the core block 10 are flush with the two end faces of the CPG matrix 20, exposed to the outside.

[0030] In some embodiments, the material of the core block 10 is the same as or compatible with the material of the adhesive particles to ensure a strong interfacial bond during sintering.

[0031] In some embodiments, the CPG substrate 20 has three-dimensional interconnected pores.

[0032] In some embodiments, the environment for oligonucleotide synthesis includes a strong acid environment, a strong base environment, an organic solvent environment, etc.

[0033] In some embodiments, the core 10 is an inert polymer material.

[0034] Specifically, the inert polymer material is polypropylene, ultra-high molecular weight polyethylene, or high-density polyethylene.

[0035] In some embodiments, core blocks 10 of a preset size are processed by mechanically cutting plates or rods.

[0036] In some embodiments, the core block 10 may be cylindrical, sheet-shaped, or the like.

[0037] For example, the core block 10 can be processed into a cylindrical structure with a diameter of φ1.5mm × 3mm.

[0038] In some embodiments, the chip 10 is laterally completely surrounded by the CPG substrate 20. Because the chip 10 is laterally completely surrounded by the CPG substrate 20, it can be physically protected.

[0039] Specifically, the core block 10 is located at the center of the CPG composite filter element 1.

[0040] S2, laser marking is performed on the exposed part of the core block 10 to form the unique identification information 11 of the CPG composite filter element 1.

[0041] Because the CPG composite filter element 1 has unique identification information 11, its synthesis path can be set before the synthesis operation. During the synthesis process based on the CPG composite filter element 1, the unique identification information 11 can be scanned before each synthesis step to identify the current synthesis task. After all synthesis operations are completed, the synthesis path based on the CPG composite filter element 1 can be traced using the unique identification information 11. This avoids confusion of the CPG composite filter element 1 and the resulting errors in recording the synthesis sequence, enabling the tracking and tracing of the CPG composite filter element 1.

[0042] In some embodiments, the chip 10 has a first end face 12, which is exposed to the outside, and laser marking is performed on the first end face 12 to form unique identification information 11.

[0043] Specifically, the first end face 12 is flush with the corresponding end face 22 of the CPG substrate 20 (i.e., the two are located on the same plane) or recessed relative to the corresponding end face 22 of the CPG substrate 20 (assuming that the corresponding end face 22 of the CPG substrate 20 is the upper surface, and the first end face 12 is the upper surface of the core block 10 and is recessed relative to the upper surface of the CPG substrate 20).

[0044] Specifically, the chip 10 has a second end face 13 opposite to the first end face 12. The second end face 13 is exposed, and laser marking is performed on the second end face 13 to form unique identification information 11. That is to say, the first end face 12 and the second end face 13 of the chip 10 are marked simultaneously to form the same unique identification information 11, which facilitates rapid identification.

[0045] More specifically, the second end face 13 is flush with the corresponding end face 23 of the CPG substrate 20 (i.e., the two are located on the same plane) or recessed relative to the corresponding end face 23 of the CPG substrate 20.

[0046] It should be noted that this application does not limit the specific shape and exposure method of the core block 10, as long as it is possible to laser mark on the core block 10 without significantly affecting the subsequent use of the CPG composite filter element 1.

[0047] In some embodiments, the unique identification information 11 is a QR code, a micro-character array, or a code.

[0048] In some embodiments, the CPG composite filter element 1 is fixed on a positioning fixture, and a laser marking machine is used to mark the exposed part of the core block 10, assigning it unique identification information 11. The marking process only acts on the area where the core block 10 is located and does not involve the CPG substrate 20, avoiding damage to the CPG pore structure by high-energy laser. At the same time, since the marking is performed after high-temperature sintering, the integrity of the encoded information is also avoided from being destroyed during the high-temperature sintering process.

[0049] In some embodiments, the laser marking parameters are: power 15W-25W, marking speed 300-800mm / s, and marking depth 0.02mm-0.08mm. The temperature of the CPG composite filter element 1 is monitored in real time during the marking process to ensure it does not exceed 50℃, thus avoiding high temperatures affecting the structural stability of the filter element.

[0050] In the specific example, the laser marking parameters were: power 20W, marking speed 500mm / s, and marking depth 0.05mm. During the marking process, the infrared thermometer monitored and showed that the filter element temperature was 45℃, which is below the 50℃ threshold.

[0051] In this embodiment, the processed CPG filter element is a CPG composite filter element 1, comprising a core block 10 and a CPG matrix 20 integrally formed on the outside of the core block 10. The core block 10 is resistant to the environment of the oligonucleotide synthesis process and is at least partially exposed. The exposed part of the core block 10 is laser-marked to form unique identification information 11 for the CPG composite filter element 1. Therefore, in the subsequent oligonucleotide solid-phase synthesis process, the presence of the CPG matrix 20 will not affect the permeability of the reagents, and the CPG composite filter element 1 can be tracked based on the unique identification information 11 on the core block 10, enabling traceability of the synthesis based on the CPG composite filter element 1. Moreover, this embodiment avoids the problems of easy detachment, corrosion, or blurring of markings caused by traditional marking methods, leading to information loss, and also avoids the destruction of the integrity of the unique identification information 11 by high-temperature sintering or the destruction of the pore structure of the CPG composite filter element 1 by high-energy laser.

[0052] The above-disclosed examples are merely preferred embodiments of this application and should not be construed as limiting the scope of this application. Therefore, any equivalent variations made in accordance with the claims of this application shall fall within the scope of this application.

Claims

1. A method for manufacturing a CPG filter element, characterized in that, include: A CPG composite filter element is manufactured, comprising a core block and a CPG matrix integrally formed on the outside of the core block, wherein the core block is resistant to the environment of the oligonucleotide synthesis process and is at least partially exposed to the outside; Laser marking is performed on the exposed portion of the core block to form unique identification information for the CPG composite filter element.

2. The CPG filter element manufacturing method according to claim 1, characterized in that, The environment during the oligonucleotide synthesis process includes strong acid environment, strong base environment, and organic solvent environment.

3. The CPG filter element manufacturing method according to claim 1, characterized in that, The core block is made of an inert polymer material.

4. The CPG filter element manufacturing method according to claim 3, characterized in that, The inert polymer material is polypropylene, ultra-high molecular weight polyethylene, or high-density polyethylene.

5. The method for manufacturing a CPG filter element according to claim 1, characterized in that, The process of producing the CPG composite filter element includes: The core block is processed; The core block is placed in a predetermined position within the cavity of the mold; A mixture of CPG particles and adhesive particles is filled into the cavity around the core block; The mold after filling is sintered to firmly bond the CPG particles to each other and the CPG particles to the core block with adhesive, forming the CPG composite filter element. The material of the core block is the same as or compatible with the material of the adhesive particles.

6. The method for manufacturing a CPG filter element according to claim 1, characterized in that, The core is completely surrounded laterally by the CPG matrix.

7. The method for manufacturing a CPG filter element according to claim 6, characterized in that, The core block is located at the center of the CPG composite filter element.

8. The method for manufacturing a CPG filter element according to claim 6 or 7, characterized in that, The core has a first end face that is exposed to the outside. The first end face is flush with or recessed relative to the corresponding end face of the CPG substrate. The unique identification information is formed by laser marking on the first end face.

9. The method for manufacturing a CPG filter element according to claim 8, characterized in that, The core has a second end face opposite to the first end face, the second end face is exposed, and the unique identification information is formed by laser marking on the second end face.

10. The method for manufacturing a CPG filter element according to claim 1, characterized in that, The unique identification information is a QR code, a micro-character array, or a light and dark code.

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