A method for preparing a hydrophilic polymer composition and a microfluidic chip

Abstract

The present application relates to the field of microfluidic chip technology, and specifically provides a hydrophilic polymer composition and a method for preparing a microfluidic chip. The hydrophilic polymer composition comprises, by weight, 100 parts of a thermoplastic polar polymer, 10-60 parts of carboxylated chitosan, and ethylene glycol diglycidyl ether; the general formula of ethylene glycol diglycidyl ether is (CH2CHO)CH2O(CH2CHO) n CH2(OCHCH2), wherein n=1-50; the ratio of the number of moles of ethylene glycol diglycidyl ether to the number of moles of amino groups in carboxylated chitosan is 0.03-0.2:1. The hydrophilic polymer composition of the present application has good hydrophilicity and hydrophilic stability and can be used in microfluidic chips.

Description

Technical Field

[0001] The present application relates to the technical field of microfluidic chips, and in particular to a method for preparing a hydrophilic polymer composition and a microfluidic chip. Background Art

[0002] Microfluidic chips are made of inorganic materials and organic polymers. Organic polymers include polysiloxane (PDMS), polymethyl methacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), polyethylene terephthalate (PET), etc. Except for PDMS, which is a thermosetting polymer, the other organic polymers are thermoplastic polymers and can be formed by melt blending and injection molding. However, the surfaces of these organic polymers are hydrophobic. Microfluidic chips are generally used in aqueous solutions. Hydrophobic organic polymers will hinder the wetting and movement of aqueous solutions. There are at least the following methods for hydrophilic modification of microfluidic chips using organic polymers: (1) hydrophilic treatment of the surface of the organic polymer using plasma or alkaline immersion, (2) grafting hydrophilic compounds on the surface of the organic polymer, and (3) mixing hydrophilic compounds into the organic polymer. In method (1), the hydrophilicity of the treated microfluidic chip is relatively unstable and is prone to failure after being placed for a period of time; method (2) is costly, inefficient, and may change other properties of the microfluidic chip surface; the most commonly used is method (3) above, which is simple to operate and has flexible modification methods.

[0003] An existing technology is to combine microfluidics with PCR technology. Since PCR technology requires multiple heating and cooling cycles, the hydrophilicity of the surface of the microfluidic chip is required to be stable after multiple heating and cooling cycles without significant changes. Summary of the Invention

[0004] In order to solve technical problems such as unstable hydrophilicity of the surface of microfluidic chips in the prior art, the present application provides a hydrophilic polymer composition and a method for preparing a microfluidic chip.

[0005] This application adopts the following technical solutions:

[0006] A hydrophilic polymer composition, comprising, by weight, 100 parts of a thermoplastic polar polymer, 10-60 parts of carboxylated chitosan, and ethylene glycol diglycidyl ether;

[0007] The general formula of the ethylene glycol diglycidyl ether is (CH2CHO)CH2O(CH2CHO) n CH2(OCHCH2), wherein n=1-50; the ratio of the molar number of the ethylene glycol diglycidyl ether to the molar number of the amino group in the carboxylated chitosan is 0.03-0.2:1.

[0008] Preferably, the thermoplastic polar polymer is at least one selected from polymethyl methacrylate, polycarbonate, cycloolefin copolymer, polyethylene terephthalate, polystyrene and polyvinyl chloride.

[0009] Preferably, the carboxylated chitosan is selected from at least one of butyrylated chitosan, valeroylated chitosan and hexanoyl chitosan.

[0010] More preferably, the butyryl degree of the butyrylated chitosan, the valeryl degree of the valeryl chitosan, and the hexanoyl degree of the hexanoyl chitosan are 30-80%, respectively.

[0011] Preferably, the carboxylated chitosan is selected from acetylated chitosan, and the degree of acetylation is 40-80%.

[0012] More preferably, the acetylated chitosan is reacted with ethylene glycol monoglycidyl ether in advance.

[0013] More preferably, the ratio of the molar number of amino groups in the acetylated chitosan to the molar number of the ethylene glycol monoglycidyl ether is 1:0.1-0.6.

[0014] More preferably, the general formula of the ethylene glycol monoglycidyl ether is (CH2CHO)CH2O(CH2CH2O) m R, wherein m=1-30, R is selected from H, C1-C4 alkyl or C2-C6 acyl.

[0015] Preferably, the raw material components further include: 0.3-1 parts of antioxidants and 0.5-5 parts of processing aids.

[0016] A method for preparing a microfluidic chip comprises uniformly mixing the raw material combinations described in any one of the above embodiments, and performing melting, extrusion, granulation and injection molding processes to obtain the microfluidic chip.

[0017] In summary, this application has the following beneficial effects:

[0018] 1. This application uses carboxylated chitosan as a hydrophilic modifier for the microfluidic chip. Carboxylated chitosan has the characteristics of good hydrophilicity and good biocompatibility, which can give the microfluidic chip good hydrophilicity and biocompatibility. In addition, ethylene glycol diglycidyl ether is used as a compatibilizer for carboxylated chitosan, which improves the compatibility of carboxylated chitosan with the microfluidic chip material, and the obtained microfluidic chip has good transparency.

[0019] 2. Ethylene glycol diglycidyl ether acts as both a compatibilizer and a cross-linking agent. After cross-linking with carboxylated chitosan, ethylene glycol diglycidyl ether forms a semi-interpenetrating polymer network structure with the microfluidic chip material. Carboxylated chitosan is stably distributed in the microfluidic chip, effectively improving the hydrophilic stability of the microfluidic chip surface. Even after multiple hot and cold treatments, the surface hydrophilicity remains stable. DETAILED DESCRIPTION

[0020] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described in detail below.

[0021] Throughout this specification, unless otherwise specified, the terms used herein should be understood as having the same meaning as commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the event of any conflict, the present specification shall take precedence.

[0022] On the one hand, the present application provides a hydrophilic polymer composition, which comprises, by weight, 100 parts of a thermoplastic polar polymer, 10-60 parts of carboxylated chitosan and ethylene glycol diglycidyl ether;

[0023] Carboxylated chitosan refers to chitosan polymers in which the amino groups are replaced by alkyl acyl groups, such as acetyl, propionyl, butyryl, hexanoyl, etc. This application uses carboxylated chitosan as a hydrophilic modifier for microfluidic chips, which has the characteristics of good hydrophilicity and good biocompatibility. However, the compatibility of carboxylated chitosan with thermoplastic polar polymers is not very good. Therefore, ethylene glycol diglycidyl ether is added to the raw material components, which can undergo a cross-linking reaction with the carboxylated chitosan, thereby improving the compatibility with the thermoplastic polar polymer. In addition, the network structure generated by the cross-linking reaction forms a semi-interpenetrating polymer network structure with the thermoplastic polar polymer, further improving the compatibility of the carboxylated chitosan with the thermoplastic polymer. The added carboxylated chitosan will not affect the transmittance of the thermoplastic polymer. Moreover, due to the presence of the cross-linked structure, the carboxylated chitosan can stably be compatible with the thermoplastic chitosan, and the hydrophilic property is stable.

[0024] The general formula of the above-mentioned ethylene glycol diglycidyl ether is shown in formula (1): (CH2CHO)CH2O(CH2CHO) n CH2(OCHCH2) (Formula (1)), wherein n=1-50; more preferably, n=5-30.

[0025] The ratio of the mole number of ethylene glycol diglycidyl ether to the mole number of amino groups in the carboxylated chitosan is 0.03-0.2:1. By controlling the mole ratio of ethylene glycol diglycidyl ether to amino groups in the carboxylated chitosan within the above range, the degree of cross-linking can be controlled within a suitable range, which can achieve cross-linking while avoiding the processing difficulties caused by excessive cross-linking. Preferably, the mole ratio of ethylene glycol diglycidyl ether to amino groups in the carboxylated chitosan is 0.05-0.15:1. For example, the mole ratio can be 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.1:1, 0.11:1, 0.12:1, 0.13:1, 0.14:1, or 0.15:1.

[0026] In a preferred embodiment of the present application, the polar thermoplastic polymer is selected from at least one of polymethyl methacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), polyethylene terephthalate (PET), polystyrene (PS), and polyvinyl chloride (PVC). These thermoplastic polymers are commonly used materials for microfluidic chips.

[0027] In a preferred embodiment of the present application, the carboxylated chitosan is selected from at least one of butyrylated chitosan, valeroylated chitosan, and hexanoated chitosan. Chitosan molecules contain a large number of hydroxyl groups and amino groups, resulting in very high polarity and poor compatibility with conventional polymers. By adopting butyrylation, valeroylation, and / or hexanoylation, some of the amino groups on the chitosan molecules are converted to amides, which can reduce the polarity of the chitosan and improve the compatibility of the carboxylated chitosan with thermoplastic polar polymers.

[0028] In a more preferred embodiment of the present application, the butyryl degree of the butyrylated chitosan, the valeryl degree of the valeryl chitosan, and the hexanoyl degree of the hexanoated chitosan are respectively 30-80%. Taking the butyryl degree as an example, it refers to the proportion of amino groups on the chitosan that are butyrylated. For example, a butyryl degree of 50% means that 50% of the amino groups in the chitosan are butyrylated, and the remaining 50% remain unchanged. The same applies to the valeryl and hexanoyl degrees. When the butyryl degree of the butyrylated chitosan, the valeryl degree of the valeryl chitosan, and the hexanoyl degree of the hexanoated chitosan are within the above ranges, the compatibility with thermoplastic polar polymers is improved and the remaining amino groups can also undergo cross-linking reactions with ethylene glycol diglycidyl ethers. Further preferably, the butyryl degree of butyrylated chitosan, the valeryl degree of valeroylated chitosan and the hexanoyl degree of hexanoated chitosan are 35-65%, respectively. For example, they can be 35%, 37%, 40%, 43%, 45%, 48%, 50%, 52%, 55%, 57%, 60%, 63%, 65%, etc.

[0029] The above-mentioned butyrylated chitosan, valeryl chitosan, and hexanoyl chitosan can be prepared by reacting chitosan with a deacetylation degree of 97% or greater with the corresponding acylating agent (e.g., butyryl chloride, valeryl chloride, or hexanoyl chloride) according to the degree of butyryl, valeryl, or hexanoyl. Pyridine can be used as an acid-binding agent. Taking butyrylated chitosan as an example, one preparation method can be as follows: 0.001 mol of chitosan with a deacetylation degree of 99% (average degree of polymerization 1200) is added to 5 L of chloroform, 0.7 mol of pyridine is added, and the mixture is cooled in an ice-water bath. 0.63 mol of butyryl chloride is added dropwise over a period of 1 hour. After a reaction time of 6 hours, the mixture is allowed to continue to react at room temperature for another 3 hours before stopping the reaction. The crude product is filtered, extracted with acetone in a Soxhlet extractor for 8 hours, and then dried in vacuo at 60°C overnight.

[0030] In a preferred embodiment of the present application, carboxylic acid acylated chitosan is selected from acetylated chitosan, and degree of acetylation is 40-80%. The carboxylic acid acylated chitosan of the present application can also be acetylated chitosan, but the compatibility of acetylated chitosan with thermoplastic polar polymer is poor compared with the compatibility of the above-mentioned butyrylated chitosan, valeryl chitosan or hexanoyl chitosan with thermoplastic polar polymer, but due to the compatibilization produced by the reaction and crosslinking of ethylene glycol diglycidyl ether, still can realize good compatibility with thermoplastic polar polymer. More preferably, the degree of acetylation of acetylated chitosan is 40-65%, for example, degree of acetylation can be 40%, 45%, 50%, 55%, 60%, 65% etc.

[0031] In a more preferred embodiment of the present application, the acetylated chitosan is reacted with ethylene glycol monoglycidyl ether in advance, so that the compatibility of the acetylated chitosan with the thermoplastic polar polymer can be improved.

[0032] In a more preferred embodiment of the present application, the ratio of the number of moles of amino groups in the acetylated chitosan to the number of moles of ethylene glycol monoglycidyl ether is 1:0.1-0.6. This can not only improve the compatibility of the acetylated chitosan with the thermoplastic polar polymer, but also avoid that the amino groups in the acetylated chitosan are completely reacted and cannot undergo subsequent cross-linking reactions. Further preferably, the molar ratio of amino groups in the acetylated chitosan to ethylene glycol monoglycidyl ether is 1:0.15-0.45. For example, the molar ratio can be 1:0.15, 1:0.2, 1:0.25, 1:0.3, 1:0.35, 1:0.4, 1:0.45, etc. The general formula of the above-mentioned ethylene glycol monoglycidyl ether is shown in formula (2), (CH2CHO)CH2O(CH2CH2O) m R (formula (2)), wherein m=1-30, R is selected from H, C1-C4 alkyl or C2-C6 acyl.

[0033] In a preferred embodiment of the present application, the raw material components further include: 0.3-1 parts of antioxidants, 0.5-5 parts of processing aids. The processing aids may include 0.6-1 parts of heat stabilizers (such as calcium zinc stabilizers, barium zinc stabilizers, etc.), 0.5-1.5 parts of lubricants (such as zinc stearate, pentaerythritol stearate, etc.), etc.

[0034] On the other hand, the present application proposes a method for preparing a microfluidic chip, wherein the raw material combination in any of the above embodiments is uniformly mixed, and the microfluidic chip is obtained through the steps of melting, extrusion, granulation and injection molding.

[0035] In the present application, the raw material components can be mixed and then added to a twin-screw extruder for melting, extrusion, and granulation. The granulated particles are then injection molded using an injection molding machine to obtain a microfluidic chip. The melting temperature can be set according to each thermoplastic polar polymer. For example, the melt processing temperature of PVC is 160-190°C, the melt processing temperature of PC is 230-260°C, the melt processing temperature of COC is 260-290°C, and the melt processing temperature of PMMA is 170-200°C.

[0036] The technical solution of the present application is described in detail below with reference to the following examples and comparative examples. Unless otherwise specified, the parts in the following examples and comparative examples are parts by weight.

[0037] Example 1

[0038] The raw material components of the hydrophilic polymer composition are: 100 parts of PC, 30 parts of butyrylated chitosan with a butyryl degree of 45% (average degree of polymerization 940), polyethylene glycol diglycidyl ether (n=6.5 in the above formula (1)), 0.5 parts of antioxidant 168 and 0.8 parts of zinc stearate, and the molar ratio of amino groups in polyethylene glycol diglycidyl ether and butyrylated chitosan is 0.1:1.

[0039] PC and butyrylated chitosan were pre-dried to remove water. PC, butyrylated chitosan, antioxidant 168, zinc stearate, and polyethylene glycol diglycidyl ether were added to a mixer and mixed. The mixture was then transferred to a twin-screw extruder for melting, extrusion, and granulation at 230-260°C. The granulated particles were then injection molded using an injection molding machine to produce a microfluidic chip.

[0040] Example 2

[0041] The difference between Example 2 and Example 1 is that the molar ratio of polyethylene glycol diglycidyl ether to the amino group in butylated chitosan is adjusted from 0.1:1 to 0.05:1. The other steps remain unchanged.

[0042] Example 3

[0043] The difference between Example 3 and Example 1 is that the molar ratio of polyethylene glycol diglycidyl ether to the amino group in butylated chitosan is adjusted from 0.1:1 to 0.15:1. The other steps remain unchanged.

[0044] Example 4

[0045] The difference between Example 4 and Example 1 is that the average degree of polymerization n of polyethylene glycol diglycidyl ether is adjusted from 6.5 to 17.6. The other steps remain unchanged.

[0046] Example 5

[0047] The difference between Example 5 and Example 1 is that the butyrylated chitosan is adjusted from 30 parts to 12 parts, and the other steps remain unchanged.

[0048] Example 6

[0049] The difference between Example 6 and Example 1 is that the butyrylated chitosan is adjusted from 30 parts to 55 parts. The other steps remain unchanged.

[0050] Example 7

[0051] The raw material components of the hydrophilic polymer composition are: 100 parts of PMMA, 25 parts of acetylated chitosan with an acetylation degree of 60% (average degree of polymerization 1340), polyethylene glycol diglycidyl ether (n=8.7 in the above formula (1)) and 0.6 parts of antioxidant 168, and the molar ratio of amino groups in polyethylene glycol diglycidyl ether and acetylated chitosan is 0.08:1.

[0052] PMMA and acetylated chitosan were pre-dried to remove water. PMMA, acetylated chitosan, antioxidant 168, and polyethylene glycol diglycidyl ether were added to a mixer and mixed. The mixture was then transferred to a twin-screw extruder and melted, extruded, and granulated at 170-200°C. The granulated particles were then injection molded using an injection molding machine to produce a microfluidic chip.

[0053] Example 8

[0054] The difference between Example 8 and Example 7 is that the acetylated chitosan is reacted with ethylene glycol monoglycidyl ether (m=1, R is methyl in formula (2)) in advance. The other steps remain unchanged.

[0055] The acetylated chitosan was reacted with ethylene glycol monoglycidyl ether in advance as follows: according to the molar ratio of amino groups in the acetylated chitosan to ethylene glycol monoglycidyl ether of 1:0.2, the acetylated chitosan was dissolved in DMF solvent 10 times its weight, and then ethylene glycol monoglycidyl ether was added, stirred and reacted at room temperature for 2 hours, then heated to 60°C and reacted for 2 hours, and DMF was removed to obtain the product.

[0056] Example 9

[0057] The difference between Example 9 and Example 8 is that in the pre-reaction between acetylated chitosan and ethylene glycol monoglycidyl ether, the molar ratio of amino groups in acetylated chitosan to ethylene glycol monoglycidyl ether is adjusted from 1:0.2 to 1:0.4. The remaining steps remain unchanged.

[0058] Comparative Example 1

[0059] The difference between Comparative Example 1 and Example 1 is that polyethylene glycol diglycidyl ether is not added in Example 1. The other steps remain unchanged.

[0060] Comparative Example 2

[0061] The difference between Comparative Example 2 and Example 1 is that polyethylene glycol diglycidyl ether in Example 1 is replaced by an equal molar amount of glutaraldehyde. The other steps remain unchanged.

[0062] Comparative Example 3

[0063] The difference between Comparative Example 3 and Example 1 is that the molar ratio of the amino groups in polyethylene glycol diglycidyl ether and butylated chitosan is adjusted from 0.1:1 to 0.23:1.

[0064] Performance Testing

[0065] Hydrophilicity test: On the surface of the microfluidic chip to be tested, take four points around the periphery and the middle point, and use a water drop angle tester to measure the water drop angle. The test results are taken as the average value and standard deviation.

[0066] Baking stability: The microfluidic chip to be tested was placed in a 90°C oven and baked for 2 hours, and the hydrophilicity test method described above was used for testing.

[0067] Thermal Cycling Stability: The microfluidic chip was subjected to 60 thermal cycling tests using the hydrophilicity test method described above. One thermal cycling cycle consisted of 90°C for 0.5 min and 10°C for 0.5 min.

[0068] Storage stability: The microfluidic chip after the hydrophilicity test was placed at room temperature for 4 months, 8 months and 12 months, and then tested again using the above hydrophilicity test method.

[0069] The results are shown in Table 1 below.

[0070] Table 1

[0071]

[0072] It can be seen from the data results in Table 1 that the hydrophilic polymer composition of the present application has good hydrophilicity and hydrophilic stability after processing. After high-temperature baking, hot and cold cycle shock and long-term storage, the hydrophilicity changes very little, and is suitable for use in microfluidic chips.

[0073] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make non-creative modifications to the present embodiment as needed, but as long as they are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. A hydrophilic polymer composition, characterized in that The raw material components include, by weight, 100 parts of thermoplastic polar polymer, 10-60 parts of carboxylated chitosan and ethylene glycol diglycidyl ether; The general formula of the ethylene glycol diglycidyl ether is (CH2CHO)CH2O(CH2CHO) n CH2(OCHCH2), where n=1-50; The ratio of the molar number of the ethylene glycol diglycidyl ether to the molar number of the amino group in the carboxylated chitosan is 0.03-0.2:

1.

2. The hydrophilic polymer composition according to claim 1, characterized in that The thermoplastic polar polymer is at least one selected from polymethyl methacrylate, polycarbonate, cycloolefin copolymer, polyethylene terephthalate, polystyrene and polyvinyl chloride.

3. The hydrophilic polymer composition according to claim 1, characterized in that The carboxylated chitosan is selected from at least one of butyrylated chitosan, valeroylated chitosan and hexanoyl chitosan.

4. The hydrophilic polymer composition according to claim 3, characterized in that The butyryl degree of the butyrylated chitosan, the valeryl degree of the valeroylated chitosan, and the hexanoyl degree of the hexanoated chitosan are respectively 30-80%.

5. The hydrophilic polymer composition according to claim 1, characterized in that The carboxylated chitosan is selected from acetylated chitosan, and the degree of acetylation is 40-80%.

6. The hydrophilic polymer composition according to claim 5, characterized in that The acetylated chitosan is reacted with ethylene glycol monoglycidyl ether in advance.

7. The hydrophilic polymer composition according to claim 6, characterized in that The ratio of the molar number of amino groups in the acetylated chitosan to the molar number of the ethylene glycol monoglycidyl ether is 1:0.1-0.

6.

8. The hydrophilic polymer composition according to claim 6, characterized in that The general formula of the ethylene glycol monoglycidyl ether is (CH2CHO)CH2O(CH2CH2O) m R, wherein m=1-30, R is selected from H, C1-C4 alkyl or C2-C6 acyl.

9. The hydrophilic polymer composition according to claim 1, characterized in that The raw material components also include: 0.3-1 parts of antioxidants and 0.5-5 parts of processing aids.

10. A method for preparing a microfluidic chip, characterized in that: The raw material combination according to any one of claims 1 to 9 is mixed uniformly, and the mixture is subjected to the steps of melting, extrusion, granulation and injection molding to obtain the microfluidic chip.

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