CN115850577A - High-biocompatibility polymer, chip and preparation method thereof - Google Patents
High-biocompatibility polymer, chip and preparation method thereof Download PDFInfo
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- CN115850577A CN115850577A CN202310126228.4A CN202310126228A CN115850577A CN 115850577 A CN115850577 A CN 115850577A CN 202310126228 A CN202310126228 A CN 202310126228A CN 115850577 A CN115850577 A CN 115850577A
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Abstract
The invention relates to the technical field of chips, and discloses a polymer with high biocompatibility, a chip and a preparation method thereof. The polymer is characterized in that the structural formula of the polymer is shown as a formula A. The invention makes polymer have compact active functional group, such as NH2, azide by free radical polymerization principle. Then fixing the polymer on the surface of the chip substrate, thereby ensuring that enough primers exist on the substrate in the chip PCR amplification process, and enabling the amplification to be carried out efficiently and uniformly; the amplified DNA cluster has higher signal-to-noise ratio when the fluorescence labeling is used.
Description
Technical Field
The invention relates to the technical field of chips, in particular to a polymer with high biocompatibility, a chip and a preparation method thereof.
Background
With the development of biotechnology, the analysis and application in the biological field is moving towards high throughput, rapidity and low cost, and more technologies rely on biochips. The chip has the characteristics of good biocompatibility, low adsorption, low steric hindrance, high density, high wetting and the like, provides an in-situ biochemical reaction environment on the solid surface, enables a complex biochemical reaction process to be rapidly and conveniently carried out on the solid surface, and simultaneously realizes high-flux and rapid biological detection, biological synthesis preparation and the like by combining with an optical information or electrical information collecting system. However, the chip in the current market has many defects and limitations, such as low density, high adsorption, poor signal-to-noise ratio, etc., which limit the application of many biotechnology, and become a bottleneck in many biotechnology fields (such as protein detection, gene sequencing, biosynthesis, etc.). Therefore, there is a need to develop a polymer, a chip and a method for preparing the same with high biocompatibility.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art described above. Therefore, the invention provides a polymer with high biocompatibility, a chip and a preparation method thereof.
In a first aspect of the invention, a polymer is provided.
Specifically, the structural formula of the polymer is shown as a formula A:
r is selected from
、/>
、/>
、/>
Any one of the above;
R 1 、R 4 each independently represents-C (O) NH 2 、-C(O)OH、
、/>
、
、/>
；
R 2 Any one of amino, epoxy, azide, alkynyl, alkenyl, nitrile, isothiocyanic, nitrile oxide, tetrazine, triazole and carboxyl is selected;
r3 is selected from any one of-NH-and-O-;
y, m and n are positive integers, and x and z are 0 or positive integers.
Preferably, x is 0 to 12000; y is 5 to 6000; m is 1 to 2000; n is 1 to 2000; z is 0 to 500.
Preferably, the molar ratio of x to y is 1-30:1.
further preferably, the molar ratio of x to y is 1-25:1.
still more preferably, the molar ratio of x, y, z is 1-25:1:0.01-0.1.
Preferably, R is selected from
；R 1 Selected from-C (O) NH 2 ；R 2 Selected from the group consisting of azide; r 3 Is selected from-NH-; r 4 Is selected from
。
Preferably, the polymer comprises
Or->
Or->
。
In a second aspect, the present invention provides a method of preparing a polymer.
Specifically, the preparation method comprises the following steps:
mixing substance B with a mixture containing R and R 2 、R 3 Putting the substance of the group into an initiator for reaction to prepare the polymer;
the substance B contains R 1 Group and/or R 4 A group.
Preferably, the reaction temperature in the preparation method is 4-65 ℃.
Further preferably, the reaction temperature in the preparation method is 10-60 ℃.
Preferably, the initiator comprises at least one of potassium persulfate, ammonium persulfate, azobisisobutyronitrile, azobisisoheptonitrile, cumene hydroperoxide, tert-butyl hydroperoxide and hydrogen peroxide.
A third aspect of the invention provides a chip.
Specifically, the chip comprises a substrate and the polymer of the first aspect grafted to the surface of the substrate.
Preferably, the substrate surface and the polymer contain reactive groups.
Preferably, the active group contained on the surface of the substrate is at least one of amino, epoxy, azide, alkynyl, alkenyl, nitrile, isothiocyanate, nitrile oxide, tetrazine, triazole and carboxyl.
Further preferably, the preparation method of the substrate surface comprises the following steps: cleaning and activating the substrate material, placing the substrate material in a closed cavity with adjustable pressure and temperature, simultaneously placing a gasifiable silane coupling agent in the cavity, and keeping the pressure at 10 -9~ 10 And (5) keeping the bar at the temperature of 25-150 ℃ for a certain time to finish the preparation of the substrate surface.
The substrate material is at least one of glass, silicon wafer and organic glass.
The washing and activating step is selected from one of the following ways:
route 1: carrying out ultrasonic treatment for 10 to 30min by absolute ethyl alcohol (30 to 60 ℃), carrying out ultrasonic treatment for 10 to 30min by 1 to 3M sodium hydroxide (30 to 60 ℃), and carrying out ultrasonic treatment for 10 to 30min by pure water (30 to 60 ℃);
route 2: and (3) heating the piranha solution (concentrated sulfuric acid: hydrogen peroxide = 7) to boil for 10 to 30min, and carrying out ultrasonic treatment on pure water (30 to 60 ℃) for 10 to 30min.
In order to further activate the surface of the chip substrate, 150W plasma treatment can be selected for 1-10 min.
The silane coupling agent is at least one selected from 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 4- (triethoxy) silylbutyronitrile, [3- (triethoxysilyl) propyl ] carbamic acid 2-propynyl ester, allyltrimethoxysilane, [ bicyclo [2.2.1] hept-5-en-2-yl ] triethoxysilane, and gamma- (2, 3-glycidoxy) propyltrimethoxysilane.
Preferably, the chip further comprises a biological component, the biological component comprising a reactive group.
Further preferably, the active group contained in the biological component is at least one of amino, epoxy, azide, alkynyl, alkenyl, nitrile, isothiocyanate, nitrile oxide, tetrazine, triazole and carboxyl.
Preferably, the biological component is selected from at least one of a nucleotide sequence, an amino acid sequence, an antigen, an antibody, a biological enzyme, a protein, and a polypeptide.
A fourth aspect of the invention provides a method of manufacturing a chip.
Specifically, the preparation method comprises the following steps:
(1) Firstly, carrying out chemical reaction on active groups on the biological components and active groups on the surface of a polymer to form covalent connection, and preparing a semi-finished product;
(2) And grafting the semi-finished product on the surface of a substrate in a covalent connection and/or a non-covalent connection mode to obtain the chip.
Preferably, the non-covalent attachment means includes hydrogen bonding, hydrophobic interaction.
A fifth aspect of the present invention provides a use of a chip for amplifying a DNA cluster.
Specifically, the isothermal amplification technique is used to generate DNA clusters on the chip.
Compared with the prior art, the invention has the following beneficial effects:
the invention makes polymer have compact active functional group, such as NH, by free radical polymerization principle 2 Azide. Then fixing the polymer on the surface of the chip substrate, thereby ensuring that sufficient primers exist on the substrate in the chip PCR amplification process, and enabling the amplification to be carried out efficiently and uniformly; the amplified DNA cluster has higher signal-to-noise ratio when the fluorescence labeling is used.
Drawings
FIG. 1 is a Gel Permeation Chromatography (GPC) chart of polymers SP1, SP2, SP 3;
FIG. 2 is a laser scan of Salus Pro on the surface of a chip substrate;
FIG. 3 is a laser scan of Salus Pro on the surface of a chip substrate;
FIG. 4 is a laser scan of Salus Pro of a chip DNA cluster.
Detailed Description
In order to make the technical solutions of the present invention more apparent to those skilled in the art, the following examples are given for illustration. It should be noted that the following examples are not intended to limit the scope of the claimed invention.
The starting materials, reagents or apparatuses used in the following examples are, unless otherwise specified, either commercially available from conventional sources or can be obtained by known methods.
Example 1
A polymer and a polymerization method thereof.
The water-soluble polymer (SP 1) is prepared by means of radical polymerization, the monomer structures (A), (B) and (C) and the polymerization reaction formula are as follows:
2000mg of (A) monomer and 58mg of (C) monomer are dissolved in 85ml of pure water to form Mix1-1, 1447mg of (B) monomer is dissolved in 15ml of DMF to form Mix1-2, 85ml of Mix1-1 and 15ml of Mix1-2 are mixed to form Mix1-3, and the mixture is fully mixed on a vortex mixer. The mixed solution Mix1-3 was filtered through a 0.22um filter membrane to remove insoluble matter. 100mg KPS was dissolved in 2ml purified water to form a 50mg/ml KSP solution. Transferring the mixed solution Mix1-3 to a 250ml three-way round bottom flask, putting a stirring magneton into the round bottom flask, and fixing the mixture in a constant temperature oil bath of a heating magnetic stirrer, wherein the temperature is set at 25 ℃, and the rotating speed is 300rpm. Using bottom nitrogen blowing, nitrogen gas was used to purge Mix1-3 30min, 1.5ml KSP solution was added, and after mixing well, 100ul TEMED reagent was added. And continuing to purify the mixed solution for 5min by using nitrogen, removing the nitrogen purification device, sealing the three-way round-bottom flask, and reacting for 2h at the set temperature of 50 ℃. After the reaction is finished, the oil bath device is removed, the airtight device is opened, air is introduced, and the reaction is stopped after stirring for 15 min. The reaction was precipitated with 10 volumes of absolute ethanol 1 times and 2 times, and finally dried in vacuo to yield 2912mg of white polymer (SP 1).
Example 2
A polymer and a polymerization method thereof.
The water-soluble polymer (SP 2) is prepared by means of radical polymerization, the monomer structures (A) (B) and the polymerization formula are as follows:
2000mg of (A) monomer was dissolved in 85ml of pure water to make up Mix2-1, 1447mg of (B) monomer was dissolved in 15ml of DMF to make up Mix2-2, 85ml of Mix2-1 and 15ml of Mix2-2 were mixed to make up Mix2-3, and mixed well on a vortex mixer. The mixed solution Mix2-3 was filtered through a 0.22um filter membrane to remove insoluble matter. 50mg KPS was dissolved in 1ml purified water to form a 50mg/ml KSP solution. The mixed solution Mix2-3 was transferred to a 250ml three-way round bottom flask, a stirring magneton was placed in the round bottom flask and fixed in a constant temperature oil bath of a heating magnetic stirrer, the temperature was set at 25 ℃, and the rotation speed was 300rpm. Nitrogen gas is blown from the bottom to purify the mixed solution Mix for 2-3 30min, 750ul KSP solution is added, and 100ul TEMED reagent is added after uniform mixing. And continuing to purify the mixed solution by using nitrogen for 5min, removing the nitrogen purification device, sealing the three-way round-bottom flask, and setting the temperature to be 30 ℃ for reaction for 2h. After the reaction is finished, the oil bath device is removed, the airtight device is opened, air is introduced, and the reaction is stopped after stirring for 15 min. The reaction was precipitated using 10 volumes of absolute ethanol, repeated 1 time, 2 times in total, and finally dried in vacuo to obtain 3200mg of white polymer (SP 2).
Example 3
A polymer and a polymerization method thereof.
The water-soluble polymer (SP 3) is prepared by means of radical polymerization, the monomer structures (A) (D) and the polymerization formula are as follows:
2000mg of (A) monomer was dissolved in 85ml of pure water to make up Mix3-1, 1215mg of (D) monomer was dissolved in 15ml of DMF to make up Mix3-2, 85ml of Mix3-1 and 15ml of Mix3-2 were mixed to make up Mix3-3, and mixed well on a vortex mixer. The mixed solution Mix3-3 was filtered through a 0.22um filter membrane to remove insoluble matter. 50mg KPS was dissolved in 1ml purified water to form a 50mg/ml KSP solution. Transferring the mixed solution Mix3-3 to a 250ml three-way round bottom flask, placing a stirring magneton in the round bottom flask, and fixing the stirring magneton in a constant temperature oil bath of a heating magnetic stirrer, wherein the temperature is set at 25 ℃ and the rotating speed is 300rpm. And (3) purifying the mixed solution Mix3-3 30min by using nitrogen gas blown from the bottom, adding 750ul of KSP solution, and adding 100ul of TEMED reagent after uniformly mixing. And continuing to purify the mixed solution by using nitrogen for 5min, removing the nitrogen purification device, sealing the three-way round-bottom flask, and setting the temperature to be 30 ℃ for reaction for 2h. After the reaction is finished, the oil bath device is removed, the airtight device is opened, air is introduced, and the reaction is stopped after stirring for 15 min. The reaction was precipitated with 10 volumes of absolute ethanol 1 time and 2 times more, and finally dried in vacuo to obtain 3218mg of white polymer (SP 3).
And (3) detection results:
as shown in fig. 1, (a) of fig. 1 shows that the average molecular weight Mw of the polymer SP1 is 32565; as shown in fig. 1 (b), the average molecular weight Mw of the polymer SP2 is 210320; as shown in fig. 1 (c), the average molecular weight Mw of the polymer SP3 was 178859.
Example 4
A chip and a preparation method thereof.
1. Preparation of a chip substrate:
and (3) performing surface coating by using a glass substrate in a chemical gas sedimentation mode. And (2) carrying out ultrasonic treatment on the glass substrate for 15min at 55 ℃ by using absolute ethyl alcohol, a 1M NaOH solution and pure water respectively, drying the surface of the glass by using a nitrogen source after the ultrasonic treatment is finished, placing the glass into a Plasma instrument, and treating the glass for 5min by using Plasma under the power of 150W. The vacuum chamber was pumped using a vacuum pump to a pressure below 10bar, 3 times displaced with nitrogen, and then placed into a 50ml centrifuge tube cap, to which 50ul of allyltrimethoxysilane was added. And (3) immediately transferring the glass subjected to the plasma treatment into the vacuum cavity, closing a door of the vacuum cavity, pumping to 1bar by using a vacuum pump, setting the temperature to 80 ℃, and setting the temperature to 25 ℃ after reacting for 2 hours. And taking out the glass sheet after cooling to obtain the glass surface coated with the alkenyl active groups. The glass sheet coated with the alkenyl is soaked in SP1 aqueous solution with the concentration of 0.1 percent (m/v), soaked for 1.5 hours at the temperature of 60 ℃, taken out and cleaned by pure water to obtain the surface modified with the (SP 1) polymer. A surface modified with (SP 1) polymer was reacted with 50uM of a 3XSSC solution of DBCO-CY5 at 60 ℃ for 1 hour, and photographed by scanning using a 640nm laser band in a Salus Pro apparatus, as shown in FIG. 2 (a).
2. Preparation of the chip:
5, the nucleic acid sequence modified with DBCO groups at the skimming side reacts with the surface modified with (SP 1) polymer, and the nucleic acid sequence is grafted to the glass surface: and (3) reacting the 3XSSC solution of 3uM DBCO-space6-A30 with the surface of the modified SP1 polymer at 60 ℃ for 2h, and cleaning the reaction product by using pure water after the reaction is finished to obtain the biochip modified with the nucleic acid sequence. The biochip was characterized by hybridization using T30-CY 5: hybridization was carried out using a 3uM T30-CY5 solution in 3XSSC at 37 ℃ for 15min, scanning and photographing were carried out using a 640nm laser band under a Salus pro instrument, and the average brightness of the pictures was analyzed by ImageJ software, and the results are shown in (a) of FIG. 3.
Example 5
A chip and a preparation method thereof.
1. Preparation of a chip substrate:
and (3) performing surface coating by using a glass substrate in a chemical gas sedimentation mode. And (2) carrying out ultrasonic treatment on the glass substrate for 15min at 55 ℃ by using absolute ethyl alcohol, a 1M NaOH solution and pure water respectively, drying the surface of the glass by using a nitrogen source after the ultrasonic treatment is finished, placing the glass into a Plasma instrument, and treating the glass for 5min by using Plasma under the power of 150W. The vacuum chamber was evacuated to a pressure below 10bar using a vacuum pump, 3 times replaced with nitrogen, and then placed in a 50ml centrifuge tube cap, to which 50ul of 2-propynyl [3- (triethoxysilyl) propyl ] carbamate was added. And (3) immediately transferring the glass subjected to the plasma treatment into the vacuum cavity, closing a door of the vacuum cavity, pumping to 1bar by using a vacuum pump, setting the temperature to 80 ℃, and setting the temperature to 25 ℃ after reacting for 2 hours. And taking out the glass sheet after cooling to obtain the glass surface coated with the alkynyl active groups. And (3) soaking the alkynyl-coated glass sheet in a (SP 2) aqueous solution with the concentration of 0.1% (m/v), soaking for 1h and 30min at the temperature of 60 ℃, taking out, and cleaning with pure water to obtain the surface modified with the (SP 2) polymer. A surface modified with (SP 2) polymer was reacted with 50uM of a 3XSSC solution of DBCO-CY5 at 60 ℃ for 1 hour, and photographed by scanning using a 640nm laser band under a Salus pro instrument, as shown in FIG. 2 (b).
2. Preparation of the chip:
5, the nucleic acid sequence modified with DBCO groups at the skimming side reacts with the surface modified with (SP 2) polymers, and the nucleic acid sequence is grafted to the glass surface: reacting the surface of the modified (SP 2) polymer with 3uM DBCO-space6-A30 of 3XSSC solution at 60 ℃ for 2h, and cleaning the reaction product by using pure water after the reaction is finished to obtain the biochip modified with the nucleic acid sequence. The biochip was characterized by hybridization using T30-CY 5: hybridization was carried out at 37 ℃ for 15min using a 3uM T30-CY5 solution in 3XSSC, scanning photographing was carried out using a 640nm laser band under a Salus Pro apparatus, and the average brightness of the pictures was analyzed by ImageJ software, and the results are shown in (b) of FIG. 3.
Example 6
A chip and a preparation method thereof.
1. Preparation of a chip substrate:
and (3) performing surface coating by using a glass substrate in a chemical gas sedimentation mode. And (2) carrying out ultrasonic treatment on the glass substrate for 15min at 55 ℃ by using absolute ethyl alcohol, a 1M NaOH solution and pure water respectively, drying the surface of the glass by using a nitrogen source after the ultrasonic treatment is finished, placing the glass into a Plasma instrument, and treating the glass for 5min by using Plasma under the power of 150W. The vacuum chamber was pumped using a vacuum pump to a pressure below 10bar, 3 times displaced with nitrogen, and then placed into a 50ml centrifuge tube cap, to which 50ul of gamma- (2, 3-epoxypropoxy) propyltrimethoxysilane was added. And (3) immediately transferring the glass subjected to the plasma treatment into the vacuum cavity, closing a door of the vacuum cavity, pumping to 1bar by using a vacuum pump, setting the temperature to 80 ℃, and setting the temperature to 25 ℃ after reacting for 2 hours. And taking out the glass sheet after cooling to obtain the glass surface coated with the epoxy active groups. The epoxy-coated glass plate was immersed in (SP 3) carbonate buffer (pH = 9.2) at a concentration of 0.1% (m/v), immersed for 8 hours at 37 ℃, taken out, and washed with pure water to obtain a surface modified with a (SP 3) polymer. The surface modified with (SP 3) polymer was reacted with 50uM NHS-CY5 carbonate buffer (pH = 9.2) at room temperature for 30min, and photographed by scanning using 640nm laser wavelength band under a Salus Pro apparatus, and the result is shown in FIG. 2 (c).
2. Preparation of the chip:
5, reacting a nucleic acid sequence modified with an epoxy group at the skimming side with the surface modified with the (SP 3) polymer, and grafting the nucleic acid sequence to the glass surface: the surface of the modified (SP 3) polymer was reacted with 3uM epoxy-space 6-a30 carbonate buffer (pH = 9.2) at 37 ℃ for 8 hours, and after the reaction was completed, the reaction product was washed with pure water to obtain a nucleic acid sequence-modified biochip. The biochip was characterized by hybridization using T30-CY 5: hybridization was carried out at 37 ℃ for 15min using a 3uM T30-CY5 solution in 3XSSC, scanning photographing was carried out using a 640nm laser band under a Salus Pro apparatus, and the average brightness of the pictures was analyzed by ImageJ software, and the results are shown in (c) of FIG. 3.
As can be seen from FIG. 2, the average brightness values of the images in FIG. 2 (a) and FIG. 2 (b) are increased because the CY5 fluorescent groups are too dense to generate "quenching" phenomenon, which indicates that there is very dense N on the substrate surface 3 A group; FIG. 2 is a schematic view of(c) The average brightness of the medium image is increased because the CY5 fluorescent group is too dense and is quenched, which indicates that the substrate surface has very dense NH 2 A group.
As can be seen from FIG. 3, the SP1, SP2 and SP3 modified surfaces after T30-CY5 hybridization all have uniform and strong fluorescence signals under the picture of Salus Pro, which indicates that the SP1, SP2 and SP3 modified surfaces can successfully covalently link oligonucleotides, and the linked oligonucleotides are uniformly distributed and have higher density.
Effect test of chips in examples 4 to 6:
the DNA clusters on the chips of examples 4-6 were generated and characterized.
1. The generation of DNA clusters is carried out by isothermal amplification techniques.
2. P1 prime-cy 5 hybrid P1 region was used to characterize cluster generation: 1uM P1 skim-cy 5 in 3XSSC was hybridized at 55 ℃ for 15min and photographed by scanning using 640nm laser at Salus Pro instrument, the results are shown in FIG. 4. FIG. 4 (a) shows a chip modified with SP1, FIG. 4 (b) shows a chip modified with SP2, and FIG. 4 (c) shows a chip modified with SP 3. As is clear from FIG. 4, all 3 types of chips can be amplified well, and the substrate surface adsorption after amplification is low, and the signal-to-noise ratio is high.
The foregoing detailed description of the preferred embodiments of the invention has been presented. It should be understood that numerous modifications and variations could be devised by those skilled in the art in light of the present teachings without departing from the inventive concepts. Therefore, any modification, equivalent replacement, improvement and the like of the technical solutions, which are made by a person skilled in the art through logic analysis, reasoning or limited experiments based on the prior art according to the concept of the present invention, should be within the protection scope determined by the claims.
Claims (10)
1. A polymer having a structural formula according to formula a:
r is selected from
、/>
、/>
、/>
Any one of the above;
R 1 、R 4 each independently represents-C (O) NH 2 、-C(O)OH、
、/>
、/>
、
；
R 2 Any one of amino, epoxy, azide, alkynyl, alkenyl, nitrile, isothiocyanic, nitrile oxide, tetrazine, triazole and carboxyl is selected;
R 3 any one selected from-NH-, -O-;
y, m and n are positive integers, and x and z are 0 or positive integers.
2. The polymer of claim 1, wherein x is 0 to 12000; y is 5 to 6000; m is 1 to 2000; n is 1 to 2000; z is 0 to 500.
3. The polymer of claim 1, wherein the molar ratio of x to y is from 1 to 30:1.
4. the polymer of claim 1, wherein the polymer comprises
Or
Or->
。
5. A process for the preparation of a polymer according to any one of claims 1 to 4, characterized in that it comprises the following steps:
mixing substance B with a mixture containing R and R 2 、R 3 Putting the substance of the group into an initiator for reaction to prepare the polymer;
said substance B contains R 1 Group and/or R 4 A group.
6. The method of claim 5, wherein the initiator comprises at least one of potassium persulfate, ammonium persulfate, azobisisobutyronitrile, azobisisoheptonitrile, cumene hydroperoxide, tert-butyl hydroperoxide, and hydrogen peroxide.
7. A chip comprising a substrate and the polymer of any one of claims 1-4 grafted to a surface of the substrate.
8. The chip of claim 7, wherein the chip further comprises a biological component; the biological component includes a reactive group.
9. The method for preparing a chip according to claim 8, comprising the steps of:
(1) Firstly, carrying out chemical reaction on active groups on the biological components and active groups on the surface of a polymer to form covalent connection, and preparing a semi-finished product;
(2) And grafting the semi-finished product on the surface of a substrate in a covalent connection and/or a non-covalent connection mode to obtain the chip.
10. Use of a chip according to any one of claims 7 to 8 for amplifying DNA clusters.
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| CN114573764A (en) * | 2020-11-30 | 2022-06-03 | 深圳市真迈生物科技有限公司 | Polymer, chip, preparation method and application thereof |
| CN115677922A (en) * | 2022-09-28 | 2023-02-03 | 深圳市曙芯生物科技有限公司 | Difunctional polymer and modification method |
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| CN115677922A (en) * | 2022-09-28 | 2023-02-03 | 深圳市曙芯生物科技有限公司 | Difunctional polymer and modification method |
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| CN116925284A (en) * | 2023-07-28 | 2023-10-24 | 珠海市大道测序生物科技有限公司 | Polymer and preparation method thereof, application of polymer in gene sequencing chip and sequencing chip |
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