CN104623978B - Dual ion charge offset type blood cell screening material and method for removing leukocytes from blood samples - Google Patents
Dual ion charge offset type blood cell screening material and method for removing leukocytes from blood samples Download PDFInfo
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- CN104623978B CN104623978B CN201410556960.6A CN201410556960A CN104623978B CN 104623978 B CN104623978 B CN 104623978B CN 201410556960 A CN201410556960 A CN 201410556960A CN 104623978 B CN104623978 B CN 104623978B
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- double ion
- electric charge
- charge deviation
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- 239000000463 material Substances 0.000 title claims abstract description 202
- 210000000601 blood cell Anatomy 0.000 title claims abstract description 139
- 210000000265 leukocyte Anatomy 0.000 title claims abstract description 75
- 210000004369 blood Anatomy 0.000 title claims abstract description 56
- 239000008280 blood Substances 0.000 title claims abstract description 56
- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000012216 screening Methods 0.000 title claims abstract description 18
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- 150000002500 ions Chemical class 0.000 claims description 206
- 210000001772 blood platelet Anatomy 0.000 claims description 35
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- 230000000694 effects Effects 0.000 claims description 25
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- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium peroxydisulfate Substances [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 3
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- ZSZRUEAFVQITHH-UHFFFAOYSA-N 2-(2-methylprop-2-enoyloxy)ethyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CC(=C)C(=O)OCCOP([O-])(=O)OCC[N+](C)(C)C ZSZRUEAFVQITHH-UHFFFAOYSA-N 0.000 description 2
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 description 2
- AMVVPENIHDSJDJ-UHFFFAOYSA-N 2-aminoethyl 5-(dimethylamino)-2-methylpent-2-enoate Chemical compound CN(C)CCC=C(C)C(=O)OCCN AMVVPENIHDSJDJ-UHFFFAOYSA-N 0.000 description 2
- QLIBJPGWWSHWBF-UHFFFAOYSA-N 2-aminoethyl methacrylate Chemical compound CC(=C)C(=O)OCCN QLIBJPGWWSHWBF-UHFFFAOYSA-N 0.000 description 2
- CSWRCKVZMMKVDC-UHFFFAOYSA-N 3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propanoate Chemical compound CC(=C)C(=O)OCC[N+](C)(C)CCC([O-])=O CSWRCKVZMMKVDC-UHFFFAOYSA-N 0.000 description 2
- CYUZOYPRAQASLN-UHFFFAOYSA-N 3-prop-2-enoyloxypropanoic acid Chemical compound OC(=O)CCOC(=O)C=C CYUZOYPRAQASLN-UHFFFAOYSA-N 0.000 description 2
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- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
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- KSOCVFUBQIXVDC-FMQUCBEESA-N p-azophenyltrimethylammonium Chemical compound C1=CC([N+](C)(C)C)=CC=C1\N=N\C1=CC=C([N+](C)(C)C)C=C1 KSOCVFUBQIXVDC-FMQUCBEESA-N 0.000 description 2
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- PNOXUQIZPBURMT-UHFFFAOYSA-M potassium;3-(2-methylprop-2-enoyloxy)propane-1-sulfonate Chemical compound [K+].CC(=C)C(=O)OCCCS([O-])(=O)=O PNOXUQIZPBURMT-UHFFFAOYSA-M 0.000 description 2
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- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 101100028791 Caenorhabditis elegans pbs-5 gene Proteins 0.000 description 1
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- VAZSKTXWXKYQJF-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)OOS([O-])=O VAZSKTXWXKYQJF-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- External Artificial Organs (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a material for screening a double-ion charge deviation type blood ball and a method for removing white blood cells from a blood sample, wherein the material for screening the double-ion charge deviation type blood ball is a copolymer consisting of a double-ion structural unit and a charged structural unit, the double-ion structural unit at least comprises a positively charged group and a negatively charged group, the distance between the positively charged group and the negatively charged group is 1-5 carbon-carbon bond lengths, and the charged structural unit and the double-ion structural unit are randomly arranged to form double-ion charge deviation. The method for removing the white blood cells from the blood sample comprises the step of enabling the blood sample to pass through the filter material made of the double-ion charge deviation type blood cell screening material, so that the purpose of removing the white blood cells from the blood sample is achieved.
Description
Technical field
The present invention relates to a kind of double ion electric charge deviation shaped material and a kind of method removing leukocyte from blood sample,
Particularly relate to a kind of double ion electric charge deviation type blood cell sieve the selection of material and one makes blood sample pass through by a kind of double ion
Electric charge deviation type blood cell sieve filter material made by the selection of material, with the method removing leukocyte from this blood sample.
Background technology
Generally, leukocyte such as can filter from blood by the filter containing fibrous material, furthermore due to platelet
And leukocyte is electronegative, surface of filter medium is typically treated as positively charged, in addition to the sponge structure (concrete dynamic modulus) utilizing filter material, and profit
Electronegative platelet and leukocyte is adsorbed with the surface of filter medium of positively charged.Additionally, in order to avoid blood coagulation or activated blood platelet,
Blood sample needs add anticoagulant, or surface of filter medium needs to carry out further surface process, in case hemostasis-coagulation.The U.S.
The 5th, 407, No. 581 exposure of patent processes the electronegative filter material in surface of blood, uses PET (polyethylene terephthalate) system
Fibrous material is as base material, then at the charged polymer of its surface grafting, so that a little negative charge of surface of filter medium band, because band
The surface of positive charge, the concentration easily causing Kallidin I (bradykinin) increases, and easily causes anaphylaxis during blood transfusion.So
And, sieve the selection of material as blood cell, need to consider selectivity, do not cause blood coagulation, anaphylaxis etc., document (U.S. Patent No. 5,
407, No. 581) in, although disclose and use positively charged, electronegative compound, the surface of available positively charged, electronegative
Surface or electroneutral surface, surface total charge show, including 3 kinds (positive electricity, negative electricity or electric neutrality), but blood is to material
The reaction of material, is not only 3 kinds, furthermore electric neutrality also includes that during charge balance, CHARGE DISTRIBUTION also can without electric charge or charge balance
Affect the blood reaction to material.Therefore, the development of blood cell sieve the selection of material, is still an important topic.
Summary of the invention
In view of foregoing invention background, in order to meet the requirement in industry, an object of the present invention is to provide a kind of double
Ionic charge deviation type blood cell sieve the selection of material, has different selectivitys to platelet, erythrocyte and leukocyte.
Another object of the present invention, is to be to provide a kind of double ion electric charge deviation type blood cell sieve the selection of material, by control
It is inclined that distance, distribution and ratio between the system charged group with different electric charges, i.e. manufacture have specific double ion electric charge
The material of difference scope, to reach the effect of blood cell screening.
Furthermore, another object of the present invention, is to be to provide a kind of double ion electric charge deviation type blood cell sieve the selection of material, from
During blood sample separation leukocyte, do not cause Coagulation test, do not result in the blocking of filter material.
It is still a further object of the present invention is to provide a kind of method removing leukocyte from blood sample, by making a blood
Liquid sample is by the filter material made by a kind of double ion electric charge deviation type blood cell provided by the present invention sieve the selection of material, to reach
To the purpose removing leukocyte from this blood sample.
In order to achieve the above object, according to one embodiment of the invention, it is provided that a kind of double ion electric charge deviation type blood cell screening
With material, the copolymer that it is double ion structural unit and electrically charged structural unit is constituted, wherein double ion structural unit
At least include that a positively charged group and an electronegative group, this positively charged group are 1～5 with the distance of this electronegative group
The length of individual carbon-carbon bond, this electrically charged structural unit and this random arrangement of double ion structural unit and constitute a pair of ionic charge
Deviation.
In an embodiment, above-mentioned double ion structural unit is derived from one of following group or above group:
Double ion phosphorio glycine betaine；Zwitter ionic phosphobetain
(R1=H or CH3；R2=O or NH；M=1～5；N=1～5)
Double ion sulfobetaines；Zwitterionic sulfobetain
(R1,=H or CH3；R2=O or NH；M=1～5；N=1～5)
Double ion carboxybetaine；Zwitterionic carboxybetain
(R1,=H or CH3；R2=O or NH；M=1～5；N=1～5).
Specifically, the such as phosphorio glycine betaine methacrylate shown in following formula
(2-methacryloyloxyethyl phosphorylcholine(phophobetaine methacrylate；
PBMA))
Sulfobetaines methacrylate shown in following formula
([2-(Methacryloyloxy)ethyl]dimethyl(3-sulfopropyl)-ammonium hydroxide
(sulfobetaine methacrylate, SBMA))
Carboxybetaine methacrylate shown in following formula
(2-Carboxy-N, N-dimethyl-N-(2 '-(methacryloyloxy) ethyl) ethanamin-ium
Inner salt (carboxybetaine methacrylate, CBMA))
Above-mentioned double ion structural unit is derived from sulfobetaines methacrylate (Sulfobetaine
Methacrylate) more satisfactory.
In an embodiment, above-mentioned electrically charged structural unit includes positively charged structural unit and electronegative structural unit
One or both of.
In an embodiment, above-mentioned positively charged structural unit is derived from one of following group or above group:
One-level amine-containing monomers
(R1,=H or CH3；R2=O or NH；M=1～5)
Secondary amine monomer
(R1,=H or CH3；R2=O or NH；R3=CH3or CH(CH3)2；M=1～5)
Tertiary amine base monomer
(R1,=H or CH3；R2=O or NH；M=1～5)
Level Four amine-containing monomers
(R1,=H or CH3；R2=O or NH；M=1～5).
Specifically, such as there is the methacrylic acid 2-aminoethyl (2-aminoethyl of following formula
methacrylate)
There is the dimethylaminoethyl acrylate methyl base aminoethyl (dimethylaminoethyl methacrylate) of following formula
[2-(methacryloxy) ethyl] trimethyl ammonium ([2-(Methacryloyloxy) ethyl]
trimethylammonium；TMA)
In an embodiment, above-mentioned electronegative structural unit is derived from one of following group or above group:
Sulfenyl monomer
Carboxylic monomer
Specifically, such as there is the methacrylic acid 3-sulphopropyl (3-sulfopropyl of following formula
methacrylate)
There is the methacrylic acid 2-carboxyethyl (2-Carboxyethyl acrylate) of following formula
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 5%～
34%, this double ion electric charge deviation type blood cell sieves the selection of material to platelet without activation effect.Above-mentioned electric charge deviation range, is right
When the summation of double ion structural unit and positively charged structural unit is 100 moles of %, the mol ratio of double ion structural unit
Example is 70～90 moles of %, and the molar ratio of positively charged structural unit is constituted by 30～10 moles of %.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 35%～
75%, this double ion electric charge deviation type blood cell sieve the selection of material has activation effect to platelet.Above-mentioned electric charge deviation range is
When being 100 moles of % to the summation of double ion structural unit and positively charged structural unit, the mol ratio of double ion structural unit
Being 30～60 moles of %, the molar ratio of positively charged structural unit is constituted by 70～40 moles of %.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have negative electric charge deviation range be 15%～
59%, this double ion electric charge deviation type blood cell sieves the selection of material to platelet without activation effect.Above-mentioned electric charge deviation range is right
When the summation of double ion structural unit and electronegative structural unit is 100 moles of %, the molar ratio of double ion structural unit
Being 51～80 moles of %, the molar ratio of electronegative structural unit is constituted by 49～20 moles of %.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have negative electric charge deviation range be 60%～
90%, this double ion electric charge deviation type blood cell sieve the selection of material has activation effect to platelet.Above-mentioned electric charge deviation range, be
When being 100 moles of % to the summation of double ion structural unit and electronegative structural unit, double ion structural unit mole
Ratio is 30～50 moles of %, and the molar ratio of electronegative structural unit is constituted by 70～50 moles of %.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 5%～
35%, after a sample containing leukocyte is by this double ion electric charge deviation type blood cell sieve the selection of material, the leukocyte in sample
By this double ion electric charge deviation type blood cell screening filtration of material.Above-mentioned electric charge deviation range, be to double ion structural unit with
And the summation of positively charged structural unit is when being 100 moles of %, the molar ratio of double ion structural unit is 70～90 moles of %,
The molar ratio of positively charged structural unit is constituted by 30～10 moles of %.
In an embodiment, above-mentioned double ion structural unit, the distance of this positively charged group and this electronegative group be 2～
The length of 4 carbon-carbon bonds is more satisfactory.
Furthermore, according to another embodiment of the present invention, it is provided that a kind of double ion electric charge deviation type blood cell sieve the selection of material, it is
The copolymer that positively charged structural unit and electronegative structural unit are constituted, wherein this positively charged structural unit is electronegative with this
The distance of structural unit is the length of 1～5 carbon-carbon bond, and this positively charged structural unit and this electronegative structural unit are random
Arrange and constitute a pair of ionic charge deviation.
In an embodiment, above-mentioned positively charged structural unit, it is derived from one of following group or above group:
One-level amine-containing monomers
(R1,=H or CH3；R2=O or NH；M=1～5),
Secondary amine monomer
(R1,=H or CH3；R2=O or NH；R3=CH3or CH(CH3)2；M=1～5),
Tertiary amine base monomer
(R1,=H or CH3；R2=O or NH；M=1～5),
Level Four amine-containing monomers
(R1,=H or CH3；R2=O or NH；M=1～5).
There is the methacrylic acid 2-aminoethyl (2-aminoethyl methacrylate) of following formula
There is the dimethylaminoethyl acrylate methyl base aminoethyl (dimethylaminoethyl methacrylate) of following formula
[2-(methacryloxy) ethyl] trimethyl ammonium ([2-(Methacryloyloxy) ethyl]
trimethylammonium；TMA)
In an embodiment, above-mentioned electronegative structural unit, it is derived from one of following group or above group:
Sulfenyl monomer
Example: 3-sulfopropyl methacrylate (SA)
Carboxylic monomer
Example: 2-Carboxyethyl acrylate
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 15%～
65%, this double ion electric charge deviation type blood cell sieve the selection of material has activation effect to platelet.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have negative electric charge deviation range be 50%～
80%, this double ion electric charge deviation type blood cell sieves the selection of material to platelet without activation effect.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 20%～
70%, after a sample containing leukocyte is by this double ion electric charge deviation type blood cell sieve the selection of material, the leukocyte in sample
By this double ion electric charge deviation type blood cell screening filtration of material.
The brightest another execute example, it is provided that the method removing leukocyte in blood product, blood
The method removing leukocyte in product is to make blood product lead to a pair of ionic charge deviation type blood cell to sieve the selection of material institute
The material become, wherein, the big what of leukocyte removal rate 95% of material.Above-mentioned method further includes row one fixed routine,
Make double ion electric charge deviation type blood cell sieve the selection of material on the surface of a base material, containing material energy formed by base material
More change places and other material accessory row, the bright described blood product of basis that therefore can be more general remove
The method of leukocyte is used in the territory of phase.
In an embodiment, described double ion electric charge deviation type blood cell sieve the selection of material, its be double ion structural unit with
And the copolymer that electrically charged structural unit is constituted, wherein double ion structural unit at least includes a positively charged group and one
The length that distance is 1～5 carbon-carbon bond of electronegative group, this positively charged group and this electronegative group, this electrically charged structure
Unit and this random arrangement of double ion structural unit and constitute a pair of ionic charge deviation.
In an embodiment, described double ion electric charge deviation type blood cell sieve the selection of material, its be positively charged structural unit with
And the copolymer that electronegative structural unit is constituted, wherein this positively charged structural unit with the distance of this electronegative structural unit is
The length of 1～5 carbon-carbon bond, this positively charged structural unit and this random arrangement of electronegative structural unit and constitute a pair of from
Charge of the electron deviation.
The method removing leukocyte from blood sample of the present invention further includes a fixed routine, make above-mentioned double from
Charge of the electron deviation type blood cell sieve the selection of material bond, can be simpler containing the filter material made by this base material on the surface of a base material
And other doctor's material pipe fitting assemble, and the leukocyte removal rate of this filter material is also more than 95%.
In an embodiment, this fixed routine is plasma-based induction Surface grafting reaction or the bridge formation grafting of physics inducement surface.
In an embodiment, this base material comprises polypropylene fibre and polyester fiber, it is preferable that described base material is that polypropylene is fine
Dimension.
In an embodiment, it is a thin film by the filter material made by above-mentioned fixed routine.
In an embodiment, described blood sample comprises the dense liquid of whole blood, Packed Red Blood Cells and platelet.
In order to effectively remove leukocyte and the requirement met in industry regulation from blood sample, described filter material white
Blood cell removal rate have to be larger than 95%.By adjusting the double ion electric charge deviation type blood cell sieve the selection of material changing this filter material of composition
In double ion structural unit, positively charged structural unit or the combination of electronegative structural unit and molar ratio, can make described
Filter material has the leukocyte removal rate effect more than 95%.
In an embodiment, above-mentioned double ion structural unit is double ion sulfobetaines；Zwitterionic
sulfobetaine
(R1 ,=H or CH3；R2=O or NH；M=1～5；N=1～5)
Preferably, described double ion sulfobetaines is sulfobetaines methacrylate [2-
(Methacryloyloxy)ethyl]dimethyl(3-sulfopropyl)-ammonium hydroxide
(sulfobetaine methacrylate, SBMA)
In an embodiment, above-mentioned positively charged structural unit is [2-(methacryloxy) ethyl] trimethyl ammonium ([2-
(Methacryloyloxy)ethyl]trimethylammonium；TMA)
In an embodiment, above-mentioned electronegative structural unit, it is derived from one of following group or above group:
Sulfenyl monomer
Example: methacrylic acid 3-sulphopropyl 3-sulfopropyl methacrylate (SA)
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material is 60 moles of % [2-(methacryloxypropyls
Base) ethyl] trimethyl ammonium ([2-(Methacryloyloxy) ethyl] trimethylammonium；TMA) and 40 moles of %'s
The copolymer that methacrylic acid 3-sulphopropyl (3-sulfopropylmethacrylate) is constituted, made by this copolymer
Filter material have more than 97% leukocyte removal rate.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material is 70 moles of % [2-(methacryloxypropyls
Base) second very] trimethyl ammonium ([2-(Methacryloyloxy) ethyl] trimethylammonium；TMA) and 30 moles of %'s
The copolymer that methacrylic acid 3-sulphopropyl (3-sulfopropylmethacrylate) is constituted, made by this copolymer
Filter material have more than 95% leukocyte removal rate.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material is 80 moles of % [2-(methacryloxypropyls
Base) ethyl] trimethyl ammonium ([2-(Methacryloyloxy) ethyl] trimethylammonium；TMA) and 20 moles of %'s
The copolymer that methacrylic acid 3-sulphopropyl (3-sulfopropylmethacrylate) is constituted, made by this copolymer
Filter material have more than 99.9% leukocyte removal rate.
In another embodiment, double ion electric charge deviation type blood cell sieve the selection of material is 30 moles of % [2-(methacryls
Epoxide) ethyl] trimethyl ammonium ([2-(Methacryloyloxy) ethyl] trimethylammonium；TMA) and 70 moles of %
Methacryloxy thetine SBMA (2-(Methacryloyloxy) ethyl] dimethyl (3-
Sulfopropyl)-ammonium hydroxide) copolymer that constituted, the filter material made by this copolymer have 99% with
On leukocyte removal rate.
By technique scheme, the present invention at least has following advantages and beneficial effect: according to the double ion of the present invention
Electric charge deviation type blood cell sieve the selection of material, available sieves the selection of material as blood cell, charged by control with different electric charges
Distance, distribution and ratio between group, meets the demand that various blood cell separates.Furthermore, provided according to the present invention
The method removing leukocyte in blood product, the big what of leukocyte removal rate 95% of the method, can reach from blood efficiently
Liquid sample removes the purpose of leukocyte.
Described above is only the general introduction of technical solution of the present invention, in order to better understand the technological means of the present invention,
And can be practiced according to the content of description, and in order to allow the above and other objects, features and advantages of the present invention can
Become apparent, below especially exemplified by preferred embodiment, and coordinate accompanying drawing, describe in detail as follows.
Accompanying drawing explanation
Fig. 1 represents double ion electric charge deviation type blood cell sieve the selection of material (copolymer I) according to the embodiment of the present invention one
Double ion electric charge deviation and platelet, erythrocyte and the bar diagram of leukocyte Adsorption experimental results.
Fig. 2 represents double ion electric charge deviation type blood cell sieve the selection of material (copolymer II) according to the embodiment of the present invention two
Double ion electric charge deviation and platelet, erythrocyte and the bar diagram of leukocyte Adsorption experimental results.
Detailed description of the invention
For the present invention aforementioned and other technology contents, feature and effect, in following cooperation with reference to graphic one preferable
In the detailed description of embodiment, can clearly present.In order to enable to understand up hill and dale the present invention, will propose in following description
Detailed step and composition thereof.It is apparent that the execution of the present invention be not limited to that this skilled person is familiar with special carefully
Joint.On the other hand, it is thus well known that composition or step are not described in details, to avoid the limit causing the present invention unnecessary
System.Presently preferred embodiments of the present invention will be described in detail as follows, but in addition to these describe in detail, the present invention can also be extensively
Ground is implemented in other embodiments, and the scope of the present invention is not limited, its with claims in the range of standard.
In the application of blood treatment, prior art (U.S. Patent No. 5,407, No. 581), though disclosing relevant electrically charged base
Group is as the filter material of blood treatment, and particularly the surface of filter medium of band negative charge slightly, is suitably applied for blood treatment, will not
Produce anaphylaxis.But, the present inventor etc. finds total charge performance (positively charged, electronegative or electric neutrality) of surface of filter medium
Not affect the filter material selective principal element to various blood cells, that is various blood cell is (positively charged, electronegative to surface of filter medium
Or electroneutral surface) it not only 3 kinds selectivitys, furthermore, in above-mentioned document, still utilize PET (poly terephthalic acid second two
Ester) etc. porous fiber material as the base material of filter material, then the surfaction that fibrous material carries out graft polymers etc. processes,
Obtain the surface of filter medium of band negative charge slightly, reach to produce anaphylactoid effect.
But, sieve the selection of material according to the double ion electric charge deviation type blood cell of the present invention, do not use the fibers such as such as PET
Material is as the base material of blood cell screening filter material, and material itself has a porous, autologous is blood cell screening filter material, does not also have
The surfaction process etc. carrying out material processes.But, the double ion electric charge deviation type blood cell of present invention sieve the selection of material, can be with
The fibrous material of PP (polypropylene) fiber or PET etc. combines, and utilizes the purposes as blood cell screening.
According to a first embodiment of the present invention, disclose a kind of double ion electric charge deviation type blood cell sieve the selection of material, its be double from
The copolymer that sub-structural unit and electrically charged structural unit are constituted, wherein double ion structural unit is just at least including a band
The length that distance is 1～5 carbon-carbon bond of electric group and an electronegative group, this positively charged group and this electronegative group,
This electrically charged structural unit and this random arrangement of double ion structural unit and constitute a pair of ionic charge deviation.
Above-mentioned double ion structural unit sieves in the selection of material at the double ion electric charge deviation type blood cell of the present invention, except general existing
There is known bio-resistant molecule to be stained with outside glutinous effect, by the interpolation of the group of positive and negative charge, there is offer double ion electric charge inclined
The characteristic of difference, owing to electric neutrality surface includes not having the surface of charged groups and have the table of charged groups
Face, furthermore the surface of charged groups, its characteristic can with positively charged group and the distance of electronegative group and different.So, above-mentioned
Double ion structural unit at least includes a positively charged group and an electronegative group, this positively charged group and this electronegative base
The length that distance is 1～5 carbon-carbon bond of group is more satisfactory, and the length of 2～4 carbon-carbon bonds is more preferable.
In an embodiment, above-mentioned double ion structural unit is derived from one of following group or above group:
Double ion phosphorio glycine betaine；Zwitterionic phosphobetain
(R1,=H or CH3；R2=O or NH；M=1～5；N=1～5)
Example: phosphorio glycine betaine methacrylate
2-methacryloyloxyethyl phosphorylcholine(phophobetaine methacrylate；
PBMA)
Double ion sulfobetaines；Zwitterionic sulfobetain
(R1,=H or CH3；R2=O or NH；M=1～5；N=1～5)
Example: sulfobetaines methacrylate
[2-(Methacryloyloxy)ethyl]dimethyl(3-sulfopropyl)-ammonium hydroxide
(sulfobetaine methacrylate, SBMA)
Double ion carboxybetaine；Zwitterionic carboxybetain
(R1,=H or CH3；R2=O or NH；M=1～5；N=1～5)
Example: carboxybetaine methacrylate
2-Carboxy-N, N-dimethyl-N-(2 '-(methacryloyloxy) ethyl) ethanamin-ium
Inner salt (carboxybetaine methacrylate, CBMA)
In an embodiment, above-mentioned electrically charged structural unit includes positively charged structural unit and electronegative structural unit
One or both of.
In an embodiment, above-mentioned positively charged structural unit is derived from one of following group or above group:
One-level amine-containing monomers
(R1,=H or CH3；R2=O or NH；M=1～5)
Example: 2-aminoethyl methacrylate
Secondary amine monomer
(R1,=H or CH3；R2=O or NH；R3=CH3or CH(CH3)2；M=1～5)
Tertiary amine base monomer
(R1,=H or CH3；R2=O or NH；M=1～5)
Example: dimethylaminoethyl methacrylate
Level Four amine-containing monomers
(R1,=H or CH3；R2=O or NH；M=1～5)
Example: [2-(Methacryloyloxy) ethyl] trimethylammonium (TMA)
In an embodiment, above-mentioned electronegative structural unit is derived from one of following group or above group:
Sulfenyl monomer
Example: 3-sulfopropyl methacrylate (SA)
Carboxylic monomer
Example: 2-Carboxyethyl actylate
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 5%～
34%, this double ion electric charge deviation type blood cell sieves the selection of material to platelet without activation effect.Above-mentioned electric charge deviation range, is right
When the summation of double ion structural unit and positively charged structural unit is 100 moles of %, the mol ratio of double ion structural unit
Example is 70～90 moles of %, and the molar ratio of positively charged structural unit is constituted by 30～10 moles of %.
Above-mentioned electric charge deviation range, is positive charge ion monomer (example in double ion electric charge deviation type blood cell sieve the selection of material
Such as TMA) situation about being constituted with negatively charged ions monomer (such as SA), it is defined as according in x-ray photoelectron collection of illustrative plates (XPS),
The signal that crest location 399eV is contributed by the level Four nitrogen groups (N+) on positive charge ion monomer (TMA), by crest location
168eV is the element sulphur (SO on negatively charged ions monomer (SA)3-) signal contributed, respectively both signals are carried out swarming and
Calculate the integral area under crest, utilize the ratio of area to use in the screening of double ion electric charge deviation type blood cell for positive and negative charge monomer
Content shared in material.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 35%～
75%, this double ion electric charge deviation type blood cell sieve the selection of material has activation effect to platelet.Above-mentioned electric charge deviation range, be
When being 100 moles of % to the summation of double ion structural unit and positively charged structural unit, double ion structural unit mole
Ratio is 30～60 moles of %, and the molar ratio of positively charged structural unit is constituted by 70～40 moles of %.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have negative electric charge deviation range be 15%～
59%, this double ion electric charge deviation type blood cell sieves the selection of material to platelet without activation effect.Above-mentioned electric charge deviation range, is right
When the summation of double ion structural unit and electronegative structural unit is 100 moles of %, the mol ratio of double ion structural unit
Example is 51～80 moles of %, and the molar ratio of electronegative structural unit is constituted by 49～20 moles of %.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have negative electric charge deviation range be 60%～
90%, this double ion electric charge deviation type blood cell sieve the selection of material has activation effect to platelet.Above-mentioned electric charge deviation range, be
When being 100 moles of % to the summation of double ion structural unit and electronegative structural unit, double ion structural unit mole
Ratio is 30～50 moles of %, and the molar ratio of electronegative structural unit is constituted by 70～50 moles of %.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 5%～
35%, after a sample containing leukocyte is by this double ion electric charge deviation type blood cell sieve the selection of material, the leukocyte in sample
By this double ion electric charge deviation type blood cell screening filtration of material.Above-mentioned electric charge deviation range, be to double ion structural unit with
And the summation of positively charged structural unit is when being 100 moles of %, the molar ratio of double ion structural unit is 70～90 moles of %,
The molar ratio of positively charged structural unit is constituted by 30～10 moles of %.
Furthermore, according to a second embodiment of the present invention, a kind of double ion electric charge deviation type blood cell sieve the selection of material, its be band just
The copolymer that electricity structural unit and electronegative structural unit are constituted, wherein this positively charged structural unit and this electronegative structure
The distance of unit is the length of 1～5 carbon-carbon bond, this positively charged structural unit and this random arrangement of electronegative structural unit
And constitute a pair of ionic charge deviation.
The present embodiment and first embodiment difference, be that the present embodiment only uses positively charged structural unit and band negative
Electricity structural unit constitutes the copolymer of the present invention, is 1～5 by making positively charged structural unit with the distance of electronegative structural unit
The length of individual carbon-carbon bond, such as, select specific group, positively charged structural unit and the random arrangement of electronegative structural unit
And constitute a pair of ionic charge deviation.
In an embodiment, above-mentioned positively charged structural unit, it is derived from one of following group or above group:
One-level amine-containing monomers
(R1,=H or CH3；R2=O or NH；M=1～5)
Example: 2-aminoethyl methacrylate
Secondary amine monomer
(R1,=H or CH3；R2=O or NH；R3=CH3or CH(CH3)2；M=1～5.
Tertiary amine base monomer
(R1,=H or CH3；R2=O or NH；M=1～5)
Example: dimethylaminoethyl methacrylate
Level Four amine-containing monomers
(R1,=H or CH3；R2=O or NH；M=1～5)
Example: [2-(Methacryloyloxy) ethyl] trimethy] ammonium (TMA)
In an embodiment, above-mentioned electronegative structural unit, it is derived from one of following group or above group:
Sulfenyl monomer
Example: 3-sulfopropyl methacrylate
Carboxylic monomer
Example: 2-Carboxyethyl acrylate
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 15%～
65%, this double ion electric charge deviation type blood cell sieve the selection of material has activation effect to platelet.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have negative electric charge deviation range be 50%～
80%, this double ion electric charge deviation type blood cell sieves the selection of material to platelet without activation effect.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material have positive electric charge deviation range be 20%～
70%, after a sample containing leukocyte is by this double ion electric charge deviation type blood cell sieve the selection of material, the leukocyte in sample
By this double ion electric charge deviation type blood cell screening filtration of material.It is more preferably to positively charged structural unit and electronegative structure
When the summation of unit is 100 moles of %, the molar ratio of positively charged structural unit is 80 moles of %, rubbing of electronegative structural unit
Your ratio is 20 moles of %.
According to still another embodiment of the invention, it is provided that a kind of method removing leukocyte from blood sample, should be from blood
The method removing leukocyte in sample is to make a blood sample made by a pair of ionic charge deviation type blood cell sieve the selection of material
The filter material become, wherein, the leukocyte removal rate of this filter material is more than 95%.Above-mentioned method further includes and carries out a fixed routine,
Make this double ion electric charge deviation type blood cell sieve the selection of material bond on the surface of a base material, containing the filter material energy made by this base material
Doctor's material accessory with other assembles more simply.
In an embodiment, described double ion electric charge deviation type blood cell sieve the selection of material, its be double ion structural unit with
And the copolymer that electrically charged structural unit is constituted, wherein double ion structural unit at least includes a positively charged group and one
The length that distance is 1～5 carbon-carbon bond of electronegative group, this positively charged group and this electronegative group, this electrically charged structure
Unit and this random arrangement of double ion structural unit and constitute a pair of ionic charge deviation.
In an embodiment, described double ion electric charge deviation type blood cell sieve the selection of material, its be positively charged structural unit with
And the copolymer that electronegative structural unit is constituted, wherein this positively charged structural unit with the distance of this electronegative structural unit is
The length of 1～5 carbon-carbon bond, this positively charged structural unit and this random arrangement of electronegative structural unit and constitute a pair of from
Charge of the electron deviation.
The described method removing leukocyte from blood sample further includes a fixed routine, makes described double ion electric charge
Deviation type blood cell sieve the selection of material bond on the surface of a base material, containing the filter material made by this base material can more simply and its
His doctor's material pipe fitting assembles, and the leukocyte removal rate of this filter material is also more than 95%.
In an embodiment, this fixed routine is plasma-based induction Surface grafting reaction or the bridge formation grafting of physics inducement surface.
In an embodiment, this base material comprises polypropylene fibre and polyester fiber, it is preferable that described base material is that polypropylene is fine
Dimension.
In an embodiment, it is a thin film by the filter material made by above-mentioned fixed routine.
In an embodiment, described blood sample comprises the dense liquid of whole blood, Packed Red Blood Cells or platelet.
In order to effectively remove leukocyte and the requirement met in industry regulation from blood sample, described filter material white
Blood cell removal rate have to be larger than 95%.By adjusting the double ion electric charge deviation type blood cell sieve the selection of material changing this filter material of composition
In double ion structural unit, positively charged structural unit or the combination of electronegative structural unit and molar ratio, can make described
Filter material has the leukocyte removal rate effect more than 95%.
In an embodiment, above-mentioned double ion structural unit is double ion sulfobetaines；Zwitterionic
sulfobetaine
(R1,=H or CH3；R2=O or NH；M=1～5；N=1～5)
Preferably, this double ion sulfobetaines is sulfobetaines methacrylate [2-(Methacryloyloxy)
Ethyl] dimethyl (3-sulfopropyl)-ammonium hydroxide (sulfobetaine methacrylate,
SBMA)
In an embodiment, above-mentioned positively charged structural unit is [2-(methacryloxy) ethyl] trimethyl ammonium ([2-
(Methacryloyloxy)ethyl]trimethylammonium；TMA)
In an embodiment, above-mentioned electronegative structural unit, it is derived from one of following group or above group:
Sulfenyl monomer
Example: methacrylic acid 3-sulphopropyl 3-sulfopropyl methacrylate (SA)
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material is 60 moles of % [2-(methacryloxypropyls
Base) ethyl] trimethyl ammonium ([2-(Methacryloyloxy) ethyl] trimethylammonium；TMA) and 40 moles of %'s
The copolymer that methacrylic acid 3-sulphopropyl (3-sulfopropylmethacrylate) is constituted, made by this copolymer
Filter material have more than 97% leukocyte removal rate.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material is 70 moles of % [2-(methacryloxypropyls
Base) ethyl] trimethyl ammonium ([2-(Methacryloyloxy) ethyl] trimethylammonium；TMA) and 30 moles of %'s
The copolymer that methacrylic acid 3-sulphopropyl (3-sulfopropyl methacrylate) is constituted, made by this copolymer
Filter material have more than 95% leukocyte removal rate.
In an embodiment, double ion electric charge deviation type blood cell sieve the selection of material is 80 moles of % [2-(methacryloxypropyls
Base) ethyl] trimethyl ammonium ([2-(Methacryloyloxy) ethyl] trimethylammonium；TMA) and 20 moles of %'s
The copolymer that methacrylic acid 3-sulphopropyl (3-sulfopropyl methacrylate) is constituted, made by this copolymer
Filter material have more than 99.9% leukocyte removal rate.
In another embodiment, double ion electric charge deviation type blood cell sieve the selection of material is 30 moles of % [2-(methacryls
Epoxide) ethyl] trimethyl ammonium ([2-(Methacryloyloxy) ethyl] trimethylammonium；TMA) and 70 moles of %
Methacryloxy thetine SBMA (2-(Methacryloyloxy) ethyl] dimethyl (3-
Sulfopropyl)-ammonium hydroxide) copolymer that constituted, the filter material made by this copolymer have 99% with
On leukocyte removal rate.
Embodiment one:
Synthesis double ion electric charge deviation type blood cell sieve the selection of material is positively charged structural unit (TMA) and electronegative structure
(wherein m and n represents the molar ratio of SA and TMA, such as SA8TMA2 to the copolymer I:SAmTMAn that unit (SA) is constituted respectively
The molar ratio of expression SA and TMA is 8: 2, the most also uses identical representation).
According to different proportion by TMA ([2-(Methacryloyloxy) ethyl] trimethylammonium
Chloride solution) it is mixed and stirred for all with SA (3-Sulfopropyl methacrylate potassium salt)
Even, the raw material (that is mixture of TMA Yu SA) then making monomeric unit is 90wt%, adds cross-linking agent NMBA (N, N-
Methylenebisacryl amide, 96%, ACROS Co. system) (8wt%) mix and blend is until after Jun Yun, by initiator
APS (1wt%) adds, and (25 DEG C) make monomer produce Raolical polymerizable with cross-linking agent at room temperature, finally add catalysis
Agent TEMED (N, N, N ', N '-Teramethylethylenediamine, 99%) (1wt%) accelerates polyreaction, will mix molten
Liquid takes out and is placed in the module preparing copolymer I, and question response is completely to form copolymer I.After two hours response time, will be altogether
Polymers II takes out and immerses in deionized water and preserve in 4 DEG C of refrigerators, utilizes deionized water to clean three times at interval of 24 hours,
To guarantee that copolymer I deposits in clean environment.The double ion electric charge deviation of each copolymer I, diiodomethane contact angle are shown in
Table 1.Diiodomethane contact angle is with diiodomethane as test liquid, drops to the surface of copolymer I to be measured, observes itself and copolymer
The contact angle on I surface.When contact angle is the biggest, represent copolymer I surface more hydrophilic；Otherwise, when contact angle becomes
Hour, then it represents that copolymer I surface relatively presents hydrophobicity.Fig. 1 represents the double ion electric charge deviation according to the embodiment of the present invention one
The double ion electric charge deviation of type blood cell sieve the selection of material (copolymer I) and platelet, erythrocyte and leukocyte Adsorption experimental results
Bar diagram.
Embodiment two:
Synthesis double ion electric charge deviation type blood cell sieve the selection of material is double ion structural unit (SBMA) and electrically charged structure
Make copolymer II:SpTMAq (the wherein p that unit (positively charged structural unit (TMA) or electronegative structural unit (SA)) is constituted
And q represents that the molar ratio of S and TMA, such as S8TMA2 represent that the molar ratio of SBMA and TMA is 8: 2 respectively, the most also use
Identical representation) or SpSAr (wherein p and r represents that the molar ratio of S and SA, such as S8SA2 represent SBMA and SA respectively
Molar ratio be 8: 2, the most also use identical representation).
According to different proportion by SBMA (2-(Methacryloyloxy) ethyl] dimethyl (3-sulfopropyl)-
Ammonium hydroxide) and TMA ([2-(Methacryloyloxy) ethyl] trimethylammonium chloride
Or SA (3-Sulfo propyl methacrylate potassium salt) is mixed and stirred for uniformly, then solution)
The raw material (that is mixture of SBMA Yu TMA or SA) making monomeric unit is 90wt%, adds cross-linking agent NMBA (8wt%) mixing
Stirring is until after Jun Yun, adding initiator Ammonium persulfate. APS (1wt%), and (25 DEG C) make monomer produce with cross-linking agent at room temperature
Raw Raolical polymerizable, finally adds catalyst TEMED (1wt%) and accelerates polyreaction, is taken out by mixed solution and inserts
In the module preparing copolymer II, question response is completely to form copolymer II.After two hours response time, copolymer II is taken
Go out and immerse in deionized water and preserve in 4 DEG C of refrigerators, utilizing deionized water to clean three times at interval of 24 hours, to guarantee altogether
Polymers II deposits in clean environment.The double ion electric charge deviation of each copolymer II, diiodomethane contact angle are shown in table 2.Fig. 2
Represent the double ion electric charge of double ion electric charge deviation type blood cell sieve the selection of material (copolymer II) according to the embodiment of the present invention two
Deviation and platelet, erythrocyte and the bar diagram of leukocyte Adsorption experimental results.
Platelet adhesion is tested, and is that glue to be measured (copolymer I or II) is placed in 24 hole culture plates, adds in every checkerwork cell dish
Place 37 DEG C of baking ovens after the PBS of 1mL and stand one hour.Take out PBS solution, in order to eliminate anticoagulant reaction and beneficially platelet
Activation, first needs to add 1mM Mg2+With 2.5mM Ca2+In containing being rich in hematoblastic human plasma solution (Platelet Rich
Plasma, PRP) in.In every checkerwork cell dish, add 1mL PRP, react after 2 hours at 37 DEG C, with PBS 5 times, by glue
The platelet washing that surface does not attaches.Then the platelet being attached on glue surface is fixed, in 24 hole culture plates
Being separately added into 1mL concentration is 2.5vol% glutaraldehyde solution, and is statically placed in 4 DEG C of refrigerators 24 hours, then is taken by glutaraldehyde solution
Repeatedly clean with PBS after going out, be dried glue with freezer dryer.After dry behaviour, carbon paste band is utilized to be fixed on microscope carrier by glue,
Plate the metal of one layer of tool electric conductivity on surface via plasma-based technology, it is little that recycling sweep electron microscope (SEM) observes blood
Plate is attached at the kenel on glue surface.
Erythrocyte adsorption experiment, is that glue to be measured (copolymer I or II) is placed in 24 hole culture plates, adds in every checkerwork cell dish
Place 37 DEG C of baking ovens after the PBS of 1mL and stand one hour.Take out PBS and in glue to be measured, add the Packed Red Blood Cells of 1mL,
Baking oven 2 hours in being placed in 37 DEG C.After Packed Red Blood Cells sucking-off purging unadsorbed blood cell with PBS, add 1mL's
2.5vol% glutaraldehyde solution, and be statically placed in 4 DEG C of refrigerators 24 hours.Last with confocal laser sweep electron microscope
(CLSM) carry out erythrocyte and be attached at the Imaging Study on glue surface.
Leukocyte adsorption experiment, is that glue to be measured (copolymer I or II) is placed in 24 hole culture plates, adds in every checkerwork cell dish
Place 37 DEG C of baking ovens after the PBS of 1mL and stand one hour.Take out PBS and in glue to be measured, add the dense liquid of leukocyte of 1mL,
Baking oven 2 hours in being placed in 37 DEG C.After dense for leukocyte liquid sucking-off purging unadsorbed blood cell with PBS, add 1mL's
2.5vol% glutaraldehyde solution, and be statically placed in 4 DEG C of refrigerators 24 hours.Last with confocal laser sweep electron microscope
(CLSM) observe leukocyte and be attached at the situation on glue surface.
By above-mentioned platelet, erythrocyte and leukocyte Adsorption experimental results, the double ion electric charge of the synthesis present invention can be learnt
During deviation type blood cell sieve the selection of material, by controlling double ion electric charge deviation, available required blood cell sifting property.Table 3 shows
Showing different double ion electric charge deviation ranges, material has different blood cell sifting properties, and it is to utilize plasma-based to lure TMA with SA
Lead surface grafting technology, prepare PPfiber thin film (pore 30um, the fiber with different SA-TMAbias range
Diameter 2um, thickness 0.5mm), place the thin film after the modify of diameter 2.5cm in the bracket, utilize and pressurize
Mode filter the dense liquid of 5cc human erythrovirus, filter effect utilizes blood analyser (LH780-LH
780Hematology Analyzer, Beckman Coulter Co.) detect its blood cell content filtered.In table 3, double ion
Electric charge deviation type blood cell sieve the selection of material SA2TMA8, when carrying out the filtration of Packed Red Blood Cells, available leukocyte removal rate is
99.98%, recovery rate of blood platelet is 3.825%, and the erythrocyte at Packed Red Blood Cells reclaims extremely useful.
Additionally, use double ion electric charge deviation type blood cell sieve the selection of material S7TMA3, (in Fig. 2, leukocyte adsorption rate is maximum
Sample), when carrying out the filtration of the dense liquid of platelet, available recovery rate of blood platelet is 99.1%, and leukocyte removal rate is
99.15%, the platelet at the dense liquid of platelet reclaims extremely useful.
Above-described embodiment be merely provided as illustrate, can carry out under without departing from the intent of the present invention and scope various deformation or
Change.
In sum, sieve the selection of material according to the double ion electric charge deviation type blood cell of the present invention, available as blood cell sieve
The selection of material, by the distance, distribution and the ratio that control between the charged group with different electric charges, material itself has many
Permeability, autologous is blood cell screening filter material, and the surfaction process etc. the most not carrying out material processes, and meets various blood cell and divides
From demand, but also can be combined with the fibrous material of PP (polypropylene) fiber or PET etc., utilize the purposes as blood cell screening.
Though the present invention being described with specific embodiment above, but the most therefore limit the scope of the present invention, without departing from this
The main idea of invention, is familiar with this those skilled in the art understanding and can carry out various deformation or change under without departing from the intent of the present invention and scope.
Additionally any embodiment or the claim of the present invention is not necessary to reach the whole purposes that disclosed herein or advantage or spy
Point.
Claims (17)
1. double ion electric charge deviation type blood cell sieve the selection of material, it is characterised in that it is double ion structural unit and charged
The copolymer that lotus structural unit is constituted, wherein double ion structural unit at least include a positively charged group and one electronegative
Group, the length that distance is 1～5 carbon-carbon bond of this positively charged group and this electronegative group, this electrically charged structural unit with
This random arrangement of double ion structural unit and constitute a pair of ionic charge deviation, and this electrically charged structural unit includes positively charged
One or both of lotus structural unit and electronegative structural unit, and this double ion electric charge deviation type blood cell sieve the selection of material tool
Having positive electric charge deviation range is 5%～34%, and this double ion electric charge deviation type blood cell sieves the selection of material to platelet without activation
Effect.
Double ion electric charge deviation type blood cell the most according to claim 1 sieve the selection of material, it is characterised in that to double ion structure
Make the summation of unit and positively charged structural unit when being 100 moles of %, the molar ratio of double ion structural unit be 70～
90 moles of %, the molar ratio of positively charged structural unit is 30～10 moles of %.
3. double ion electric charge deviation type blood cell sieve the selection of material, it is characterised in that it is double ion structural unit and charged
The copolymer that lotus structural unit is constituted, wherein double ion structural unit at least include a positively charged group and one electronegative
Group, the length that distance is 1～5 carbon-carbon bond of this positively charged group and this electronegative group, this electrically charged structural unit with
This random arrangement of double ion structural unit and constitute a pair of ionic charge deviation, and this electrically charged structural unit includes positively charged
One or both of lotus structural unit and electronegative structural unit, and this double ion electric charge deviation type blood cell sieve the selection of material tool
Having positive electric charge deviation range is 35%～75%, and this double ion electric charge deviation type blood cell sieve the selection of material has work to platelet
Change effect.
Double ion electric charge deviation type blood cell the most according to claim 3 sieve the selection of material, it is characterised in that to double ion structure
Make the summation of unit and positively charged structural unit when being 100 moles of %, the molar ratio of double ion structural unit be 30～
60 moles of %, the molar ratio of positively charged structural unit is 70～40 moles of %.
5. double ion electric charge deviation type blood cell sieve the selection of material, it is characterised in that it is double ion structural unit and charged
The copolymer that lotus structural unit is constituted, wherein double ion structural unit at least include a positively charged group and one electronegative
Group, the length that distance is 1～5 carbon-carbon bond of this positively charged group and this electronegative group, this electrically charged structural unit with
This random arrangement of double ion structural unit and constitute a pair of ionic charge deviation, and this electrically charged structural unit includes positively charged
One or both of lotus structural unit and electronegative structural unit, and this double ion electric charge deviation type blood cell sieve the selection of material tool
Having negative electric charge deviation range is 15%～59%, and this double ion electric charge deviation type blood cell sieves the selection of material to platelet without activation
Effect.
Double ion electric charge deviation type blood cell the most according to claim 5 sieve the selection of material, it is characterised in that to double ion structure
Make the summation of unit and electronegative structural unit when being 100 moles of %, the molar ratio of double ion structural unit be 51～
80 moles of %, the molar ratio of electronegative structural unit is 49～20 moles of %.
7. double ion electric charge deviation type blood cell sieve the selection of material, it is characterised in that it is double ion structural unit and charged
The copolymer that lotus structural unit is constituted, wherein double ion structural unit at least include a positively charged group and one electronegative
Group, the length that distance is 1～5 carbon-carbon bond of this positively charged group and this electronegative group, this electrically charged structural unit with
This random arrangement of double ion structural unit and constitute a pair of ionic charge deviation, and this electrically charged structural unit includes positively charged
One or both of lotus structural unit and electronegative structural unit, and this double ion electric charge deviation type blood cell sieve the selection of material tool
Having negative electric charge deviation range is 60%～90%, and this double ion electric charge deviation type blood cell sieve the selection of material has work to platelet
Change effect.
Double ion electric charge deviation type blood cell the most according to claim 7 sieve the selection of material, it is characterised in that to double ion structure
Make the summation of unit and electronegative structural unit when being 100 moles of %, the molar ratio of double ion structural unit be 30～
50 moles of %, the molar ratio of electronegative structural unit is 70～50 moles of %.
9. double ion electric charge deviation type blood cell sieve the selection of material, it is characterised in that it is double ion structural unit and charged
The copolymer that lotus structural unit is constituted, wherein double ion structural unit at least include a positively charged group and one electronegative
Group, the length that distance is 1～5 carbon-carbon bond of this positively charged group and this electronegative group, this electrically charged structural unit with
This random arrangement of double ion structural unit and constitute a pair of ionic charge deviation, and this electrically charged structural unit includes positively charged
One or both of lotus structural unit and electronegative structural unit, and this double ion electric charge deviation type blood cell sieve the selection of material tool
Having positive electric charge deviation range is 5%～35%, and a sample containing leukocyte is sieved by this double ion electric charge deviation type blood cell
After the selection of material, the leukocyte in sample is caught by this double ion electric charge deviation type blood cell screening filtration of material, can reach list
In the sample volume of position, the leukocyte of more than 90% catches removal rate.
Double ion electric charge deviation type blood cell the most according to claim 9 sieve the selection of material, it is characterised in that to double ion structure
Make the summation of unit and positively charged structural unit when being 100 moles of %, the molar ratio of double ion structural unit be 70～
90 moles of %, the molar ratio of positively charged structural unit is 30～10 moles of %.
11. 1 kinds of double ion electric charge deviation type blood cell sieve the selection of materials, it is characterised in that it is positively charged structural unit and band
The copolymer that negative electricity structural unit is constituted, wherein this positively charged structural unit and this random arrangement of electronegative structural unit
And constituting a pair of ionic charge deviation, this double ion electric charge deviation type blood cell sieve the selection of material has positive electric charge deviation range and is
15%～65%, this double ion electric charge deviation type blood cell sieve the selection of material has activation effect to platelet.
12. 1 kinds of double ion electric charge deviation type blood cell sieve the selection of materials, it is characterised in that it is positively charged structural unit and band
The copolymer that negative electricity structural unit is constituted, wherein this positively charged structural unit and this random arrangement of electronegative structural unit
And constituting a pair of ionic charge deviation, this double ion electric charge deviation type blood cell sieve the selection of material has negative electric charge deviation range and is
50%～80%, this double ion electric charge deviation type blood cell sieves the selection of material to platelet without activation effect.
13. 1 kinds of double ion electric charge deviation type blood cell sieve the selection of materials, it is characterised in that it is positively charged structural unit and band
The copolymer that negative electricity structural unit is constituted, wherein this positively charged structural unit and this random arrangement of electronegative structural unit
And constituting a pair of ionic charge deviation, this double ion electric charge deviation type blood cell sieve the selection of material has positive electric charge deviation range and is
20%～70%, after a sample containing leukocyte is by this double ion electric charge deviation type blood cell sieve the selection of material, in sample
Leukocyte is caught by this double ion electric charge deviation type blood cell screening filtration of material, can reach in unit sample volume more than 90%
Leukocyte catch removal rate.
14. 1 kinds of methods removing leukocyte from blood sample, it is characterised in that described removes white blood from blood sample
The method of ball is to make a blood sample sieve the selection of material, this double ion electric charge deviation type by a pair of ionic charge deviation type blood cell
Blood cell sieve the selection of material is 30 moles of % [2-(methacryloxy) ethyl] trimethyl ammonium and the methyl-prop of 70 moles of %
The copolymer that alkene acyloxy thetine is constituted, the filter material made by this copolymer has the leukocyte of more than 99% and removes
Rate.
15. 1 kinds of methods removing leukocyte from blood sample, it is characterised in that described removes white blood from blood sample
The method of ball is to make a blood sample sieve the selection of material, this double ion electric charge deviation type by a pair of ionic charge deviation type blood cell
Blood cell sieve the selection of material is 60 moles of % [2-(methacryloxy) ethyl] trimethyl ammonium and the methyl-prop of 40 moles of %
The copolymer that olefin(e) acid 3-sulphopropyl is constituted, the filter material made by this copolymer has the leukocyte removal rate of more than 97%.
16. 1 kinds of methods removing leukocyte from blood sample, it is characterised in that described removes white blood from blood sample
The method of ball is to make a blood sample sieve the selection of material, this double ion electric charge deviation type by a pair of ionic charge deviation type blood cell
Blood cell sieve the selection of material is 70 moles of % [2-(methacryloxy) ethyl] trimethyl ammonium and the methyl-prop of 30 moles of %
The copolymer that olefin(e) acid 3-sulphopropyl is constituted, the filter material made by this copolymer has the leukocyte removal rate of more than 95%.
17. 1 kinds of methods removing leukocyte from blood sample, it is characterised in that described removes white blood from blood sample
The method of ball is to make a blood sample sieve the selection of material, this double ion electric charge deviation type by a pair of ionic charge deviation type blood cell
Blood cell sieve the selection of material is 80 moles of % [2-(methacryloxy) ethyl] trimethyl ammonium and the methyl-prop of 20 moles of %
The copolymer that olefin(e) acid 3-sulphopropyl is constituted, the filter material made by this copolymer has the leukocyte of more than 99.9% and removes
Rate.
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| TW102141418A TWI481442B (en) | 2013-11-14 | 2013-11-14 | Zwitterionic-bias material for blood cell selection |
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| US11833289B2 (en) * | 2016-11-09 | 2023-12-05 | Puriblood Medical Co., Ltd. | Polymer and device for capturing or separating leucocytes, manufacturing method and use thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1036513A (en) * | 1988-02-17 | 1989-10-25 | 帕尔公司 | Method for separating leukocytes and device from platelet concentrate |
| US5190657A (en) * | 1991-07-22 | 1993-03-02 | Lydall, Inc. | Blood filter and method of filtration |
| CN1176607A (en) * | 1995-12-26 | 1998-03-18 | 旭医学株式会社 | Filter medium for leukocyte removal |
| CN102397724A (en) * | 2010-09-16 | 2012-04-04 | 私立中原大学 | Filter medium for leukocyte removal and filter method |
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| EP2069412B1 (en) * | 2006-08-07 | 2019-01-02 | University of Washington | Mixed charge copolymers and hydrogels |
| EP2496267A4 (en) * | 2009-11-06 | 2016-02-17 | Univ Washington Ct Commerciali | Zwitterionic polymer bioconjugates and related methods |
| US8288472B2 (en) * | 2009-12-29 | 2012-10-16 | Chung-Yuan Christian University | Antibiofouling nonionic-zwitterionic copolymer |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1036513A (en) * | 1988-02-17 | 1989-10-25 | 帕尔公司 | Method for separating leukocytes and device from platelet concentrate |
| US5190657A (en) * | 1991-07-22 | 1993-03-02 | Lydall, Inc. | Blood filter and method of filtration |
| CN1176607A (en) * | 1995-12-26 | 1998-03-18 | 旭医学株式会社 | Filter medium for leukocyte removal |
| CN102397724A (en) * | 2010-09-16 | 2012-04-04 | 私立中原大学 | Filter medium for leukocyte removal and filter method |
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