CN101279200B - Blood separating mechanism for filtering leucocyte and manufacturing method thereof - Google Patents

Blood separating mechanism for filtering leucocyte and manufacturing method thereof Download PDF

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Publication number
CN101279200B
CN101279200B CN2008100181389A CN200810018138A CN101279200B CN 101279200 B CN101279200 B CN 101279200B CN 2008100181389 A CN2008100181389 A CN 2008100181389A CN 200810018138 A CN200810018138 A CN 200810018138A CN 101279200 B CN101279200 B CN 101279200B
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China
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dash receiver
filter
cover plate
blood
filter plate
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CN2008100181389A
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CN101279200A (en
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王朝晖
蒋庄德
叶鹏
郭光�
张鑫
王小章
李柯润
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Xian Jiaotong University
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Xian Jiaotong University
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Abstract

The invention relates to a blood processor and discloses a blood processor for filtrating leukocytes and a manufacturing method thereof. The blood processor comprises a dash receiver, a filter board and a cover board that are sequentially superposed, sealed and arranged together. The filter board adopts an SU-8 photosensitive emulsion material; the cover board and the dash receiver adopt a PDMS material; an infusion groove is arranged on the lower surface of the cover board; both ends of the infusion groove are respectively provided with a through hole to extract from the cover board, which is respectively used as an infusion inlet and a waste liquor outlet; a filtration pore is arranged on the filter board at a position corresponding to the infusion groove; a recycling cavity is arranged on the upper surface of the dash receiver and is provided with an infusion outlet. The blood processor adopts an organic material microlithography technology; the surface of blood channel is smooth and causes no harm to erythrocytes; the filtration pore of the filter board is of high precision size, which can completely filtrate the leukocytes in the blood with good effect.

Description

A kind of blood separating mechanism for filtering leucocyte and preparation method thereof
Technical field
The present invention relates to blood separating mechanism, relate in particular to a kind of blood separating mechanism for filtering leucocyte and preparation method thereof.
Background technology
The existing device that is applied to the blood separation mainly contains: the one, and adopting the membranaceous filter material of porous is that main body is made the Filter film type separator, the basic principle of this separator is to pass through filter membrane when blood, utilize the aperture difference of micropore on blood cell size and the filter membrane and reach the separating blood purpose, general filter membrane material adopts inorganic polymer, as multi-layered polyester fabric nonwoven cloth, high glass fiber etc.The 2nd, centrifugal blood separating mechanism.The operation principle of this separator is according to various composition density differences in the blood, proportion differs, can be behind different centrifugal actions with the leucocyte in plasma fraction and the haemocyte composition, red blood cell, blood platelet layering, through different blood bags outputs, thereby reach the purpose of separation.Yet utilize centrifugal blood separating mechanism separating blood, its leukocyte depletion rate only reaches about 70%, the red blood cell rate of recovery is also lower, this has not only caused unnecessary waste to this precious resources of blood, and, cause the blood transfusion patient serious nonhemolytic febrific reaction to occur easily owing to handle that to retain leucocyte in the red blood cell of back still too much.
And adopt the device of membrane filtration at present, because filter membrane is non-machining process and makes, aperture size distributional difference rate is up to 30%, and the distribution of filter opening on filter membrane be at random, had a strong impact on the effect that blood separates.More seriously because filter membrane channel surface roughness is excessive, and blood can scratch red blood cell by filter membrane the time, haemolysis taking place, causes valuable blood loss in vain.
Summary of the invention
The objective of the invention is for fear of the weak point of above-mentioned existing apparatus and propose that a kind of channel surface is smooth not to have injury, blood separating mechanism for filtering leucocyte that separative efficiency is high to red blood cell.
Another object of the present invention also is, the preparation method of this blood separating mechanism for filtering leucocyte is provided.
In order to achieve the above object, the present invention is achieved by the following technical solutions:
Technical scheme 1: a kind of blood separating mechanism for filtering leucocyte, it is characterized in that, comprise dash receiver, filter plate and cover plate that stacked successively sealing is installed together, described filter plate adopts the SU-8 photoresists, described cover plate and dash receiver adopt dimethyl silicone polymer PDMS, the lower surface of described cover plate is provided with the transfusion groove, transfusion groove two ends are provided with through hole respectively and draw cover plate, as transfusion inlet and waste liquid outlet, the position that described filter plate is corresponding with described transfusion groove is provided with filter opening, the upper surface of described dash receiver is provided with recycling cavity, and recycling cavity is provided with the transfusion outlet.
Device of the present invention also has following characteristics:
Described filter opening is a trough type, and the grooved width is 7-8.5 μ m.
The outline line of described transfusion groove is the sine curve of symmetry;
The outline line of described transfusion groove is a snail type curve.
Technical scheme 2: a kind of preparation method of blood separating mechanism for filtering leucocyte is characterized in that:
Make cover plate and dash receiver: make cover plate and dash receiver mould, the corresponding curing agent with it of dimethyl silicone polymer PDMS is mixed according to 10: 1 weight ratios, cast on the mould, after the extrusion forming, place in the baking oven and toasted 40~50 minutes down at 90~95 ℃, finish curing, the demoulding is stand-by;
Make filter plate: choose the silicon chip that is slightly larger than the filter plate area, the SU-8 photoresists are dripped on silicon chip, then silicon chip is placed on spin coating on the sol evenning machine, formation thickness is the even glue-line about 400um, and carries out first drying and handle; Make the filter opening pattern, and it is printed on the mask plate that transparent film is used as photoetching, adopt the SU-8 photosensitive layer after ultraviolet light is handled first drying to expose, obtain needed filter opening, carry out secondary drying then and handle; Develop at last and rinsing, the filter plate that obtains material and be the SU-8 photoresists is stand-by;
Encapsulation: cover plate, filter plate, the dash receiver made are positioned in the plasma chamber of plasma cleaner, and plasma oxidation was handled 1~2 minute, aimed at then and clamped, insert in the baking oven 80~85 ℃ down insulation got final product in 30~40 minutes.
Filter plate of the present invention adopts SU-8 photoresists material, and cover plate and dash receiver adopt dimethyl silicone polymer PDMS material, and channel surface is smooth; Moreover adopt microlithography technology to make, especially the filter opening dimensional accuracy height of filter plate is thorough, effective to the blood middle leukocytes filtering.Blood separating mechanism for filtering leucocyte with present application is compared, and the present invention has low cost of manufacture, channel surface is smooth does not have injury, separative efficiency advantages of higher to red blood cell; Its manufacturing process has that dimensional controllability is good, production efficiency is high, with low cost, characteristics such as equipment is simple.
Description of drawings
Fig. 1 is the front schematic view of blood separating mechanism for filtering leucocyte;
Fig. 2 is the enlarged drawing of A part among Fig. 1;
Fig. 3 is the schematic rear view of blood separating mechanism for filtering leucocyte;
Fig. 4 is the transfusion groove schematic diagram with sinusoidal outline line;
Fig. 5 is the transfusion groove schematic diagram with the linear outline line of snail;
Fig. 6 is the local figure of the filter opening of filter plate;
Fig. 7 is the filter plate schematic diagram of filter opening sinusoidal overall alignment;
Fig. 8 is the linear whole row's of filter opening snail a filter plate schematic diagram;
Fig. 9 is the dash receiver structural representation corresponding to filter opening sinusoidal overall alignment;
Figure 10 is the dash receiver structural representation corresponding to the linear whole row of filter opening snail.
The specific embodiment
With reference to Fig. 1,2,3, blood separating mechanism for filtering leucocyte of the present invention is made of cover plate 1, filter plate 2, dash receiver 3 three parts, and the stacked successively sealing of dash receiver 3, filter plate 2 and cover plate 1 is installed together.Described filter plate 2 adopts SU-8 photoresists material to make, described cover plate 1 and dash receiver 3 adopt dimethyl silicone polymer to make, the lower surface of described cover plate 1 is provided with the transfusion groove, transfusion groove two ends are provided with through hole respectively and draw cover plate 1, as transfusion inlet 4 and waste liquid outlet 5, the position that described filter plate 2 is corresponding with described transfusion groove is provided with filter opening, and the upper surface of described dash receiver 3 is provided with recycling cavity, and recycling cavity is provided with transfusion outlet 6.
Blood is flowed into by the inlet of the transfusion on the cover plate 14 through pressurization, in process by cover plate 1 inner transfusion groove, blood plasma, red blood cell and blood platelet can be by filter plates 2 under the effect of gravity and negative pressure in the blood, enter dash receiver 3, flow into the blood vacuum bag via the outlet of the transfusion on the dash receiver 36, and blood middle leukocytes is big because of size, can't flow into the waste liquid vacuum bag via the waste liquid outlet on the cover plate 15 by the filter opening of filter plate 2.
Cover plate 1 adopts dimethyl silicone polymer (PDMS) material to make, and its lower surface is provided with the transfusion groove, with reference to Fig. 4, the outline line of described transfusion groove can be the sine curve of symmetry, but sine curve is continuously a lead curve, so blood is steadily mobile in this runner, and blood cell is assembled few; Adopt symmetrical structure rationally to utilize material space fully, runner is longer.With reference to Fig. 5, the outline line of described transfusion groove also can be snail type curve, but this curve is continuously a lead curve, and blood flows in this runner steadily, and no blood cell is assembled; Equally, the snail structure can rationally be utilized material space fully, and runner is long.
Filter plate 2 adopts the SU-8 glue material to make, and the outline line shape of the overall alignment shape of its filter opening and cover plate 1 transfusion groove adapts, and also can be two kinds: with reference to Fig. 6, a kind of is the sinusoidal shape of symmetry; With reference to Fig. 7, another kind is a snail type curve shape.Black line partly is the filter opening zone among Fig. 6, Fig. 7, this uniform fine and closely woven trough type filter opening in zone.With reference to Fig. 8, described filter opening is a trough type, and the grooved width is 7-8.5 μ m, preferentially selects 8 μ m for use.Preferably the length direction of trough type filter opening and blood flow are to identical.Because mean corpuscular diameter is 7 μ m, the leucocyte average diameter is 10 μ m, and therefore selecting the filter opening width is that 8 μ m can be good at the filtering leucocyte, allows red blood cell pass through, and reaches the purpose of this invention; And because red blood cell has plastically deformable, the length direction of grooved filter opening and blood flow deform and reach purpose by filter opening to the consistent excessive red blood cell of original diameter that helps.
Dash receiver 3 adopts dimethyl silicone polymer PDMS material to make, the recycling cavity of dash receiver 3 is according to the overall alignment shape difference of filter plate filter opening, corresponding can be set to following two kinds: with reference to Fig. 9, be dash receiver structure corresponding to filter opening sinusoidal overall alignment, its overall structure is a matrix, red blood cell and blood plasma mixing material flow out from dash receiver transfusion outlet 6 and enter vacuum bag, and have the strong point 8 of 6 protruding round platforms in the dash receiver on average arranging according to the filter plate sinusoidal shape, help preventing that the filter plate pressurized from caving in.With reference to Figure 10, be dash receiver structure corresponding to the linear whole row of filter opening snail, its overall structure is a matrix, red blood cell and blood plasma mixing material flow out from dash receiver transfusion outlet 6 and enter vacuum bag, and arc convex is the strong point of arranging according to filter plate snail curve shape 8 in the dash receiver, helps preventing that the filter plate pressurized from caving in.
The preparation method of blood separating mechanism for filtering leucocyte of the present invention may further comprise the steps:
(1) makes cover plate and dash receiver: make cover plate and dash receiver mould, dimethyl silicone polymer PDMS and corresponding curing agent (the sylgard184 type curing agent that U.S. Dow Corning company produces) are mixed according to 10: 1 weight ratios, cast on the mould, after the extrusion forming, place in the baking oven and toasted 40~50 minutes down at 90~95 ℃, finish curing, the demoulding is stand-by;
(2) make filter plate: choose the silicon chip that is slightly larger than the filter plate area, the SU-8 photoresists are dripped on silicon chip, then silicon chip is placed on spin coating on the sol evenning machine, formation thickness is the even glue-line about 400um, and carries out first drying and handle; Make the filter opening pattern, and it is printed on the mask plate that transparent film is used as photoetching, adopt the SU-8 photosensitive layer after ultraviolet light is handled first drying to expose, obtain needed filter opening, carry out secondary drying then and handle; Develop at last and rinsing, the filter plate that obtains material and be the SU-8 photoresists is stand-by;
(3) encapsulation: the plasma chamber that cover plate, filter plate, the dash receiver of making is placed the PDC-GC-III type plasma cleaner of Chengdu permanent industry e-commerce Co., Ltd, plasma oxidation was handled 1~2 minute, aim at then and clamp, insert in the baking oven and descend insulation to get final product in 30~40 minutes at 80~85 ℃.
In preparation method of the present invention, the making of filter plate is crucial, more specifically may further comprise the steps:
(a) even glue: choose the treated silicon chip that is slightly larger than the filter plate area, the SU-8 photoresists are dripped on silicon chip, then silicon chip is placed on the sol evenning machine, under 500rpm~800rpm, carry out a spin coating of 6s~15s, carrying out 20s~30s secondary spin coating again under 1000rpm~1500rpm, is even glue-line about 400um forming thickness on the silicon chip;
(b) first drying is handled: will spare the silicon chip that glue finishes and put into baking oven, oven temperature is risen to 60~65 ℃, toast 4~10 minutes, and be incubated 3~8 minutes down at 70~75 ℃ again, and be warming up to 90~95 ℃ and kept 50~70 minutes then;
(c) exposure: make the filter opening pattern, and it is printed on the transparent film,, adopt ultraviolet light that the SU-8 photosensitive layer on the silicon chip is exposed, obtain needed filter opening with the mask plate that this film is used as photoetching;
(d) secondary drying is handled: the silicon chip after will exposing places baking oven, oven temperature is risen to 60~65 ℃, toasted 4~10 minutes, be incubated 3~8 minutes down at 70~75 ℃ again, be warming up to 90~95 ℃ and kept 25~30 minutes then, be cooled to 75~80 ℃ of insulations 50~60 minutes again, naturally cooling;
(e) develop and rinsing: cooled silicon chip is placed the developer solution 5~8 seconds that ultrasonic wave stirs earlier, in acetone soln, continue then to develop 10~12 minutes, silicon chip after developing was inserted in the aqueous isopropanol rinsing 3~5 minutes, rinse well with deionized water again and promptly obtain SU-8 photoresists filter plate.
Be another instantiation of the present invention below, make the step of filter plate, making cover plate and dash receiver and can exchange.
(1) make filter plate:
Choose silicon chip: at first choose the silicon chip that is slightly larger than the filter plate area, select 4 cun round silicon chips in this example for use, clean the greasy dirt of removal silicon chip surface and the various impurity particles of absorption; It is that the mixed solution of 98% sulfuric acid and hydrogen peroxide was handled 15 minutes that silicon chip after will cleaning is then put into mass concentration, and mixed solution is pressed H 2SO 4: H 2O 2=3: 1 mass ratio mixes; Again the silicon chip after handling is rinsed well repeatedly and inserted in the baking oven with deionized water and dry, temperature is 120 ℃, 6 minutes time.
Even glue: the SU-8 photoresists being dripped on silicon chip, then silicon chip is placed on the sol evenning machine, carry out a spin coating of 8s under 600rpm, carry out the spin coating of 30s secondary again under 1500rpm, is even glue-line about 400um forming thickness on the silicon chip.
First drying is handled: will spare the silicon chip that glue finishes and put into baking oven, oven temperature is risen to 65 ℃, toast 6 minutes, and be incubated 5 minutes down at 75 ℃ again, and be warming up to 95 ℃ and kept 70 minutes then.
Exposure: make the filter opening pattern, and it is printed on the transparent film, with the mask plate that this film is used as photoetching, the employing wavelength is that the ultraviolet light of 360nm exposes to the SU-8 photosensitive layer on the silicon chip, obtains needed filter opening, and the time for exposure is 360s.
Secondary drying is handled: the silicon chip after will expose places baking oven, and oven temperature is risen to 65 ℃, toast 5 minutes, again 75 ℃ of insulations 3 minutes down, is warming up to 95 ℃ and kept 25 minutes then, is cooled to 75 ℃ again and is incubated 60 minutes, cools off naturally.
Develop and rinsing: cooled silicon chip is placed the developer solution 8 seconds that ultrasonic wave stirs earlier, under conventional environment, continue then to develop about 25 minutes, silicon chip after developing was inserted in the aqueous isopropanol rinsing 3~5 minutes, rinse well with deionized water again and promptly obtain SU-8 photoresists filter plate.
(2) make cover plate and dash receiver:
Make cover plate and dash receiver mould: make master mold according to the filter plate global shape.
After PDMS glue and corresponding curing agent (the sylgard184 type curing agent that U.S. Dow Corning company produces) mixed by 10: 1 weight ratio.Preferably carry out the degasification of PDMS glue, be specially said mixture inserted and vacuumize 2 minutes in the vacuum cavity, exitted then 30 seconds, repeatable operation can reach good exhaust effect.
Cast and solidify: the mixed liquor of the PDMS glue after the degasification and corresponding curing agent is cast on the SU-8 master mold, after the extrusion forming, this mould is placed in the baking oven toasted 40 minutes down, finish curing at 90 ℃.
The demoulding: PDMS glue and curing agent layer after will solidifying are taken off from the SU-8 master mold, obtain cover plate and dash receiver.
(3) encapsulation:
The plasma surface oxidation processes: cover plate, filter plate, the dash receiver that will need to encapsulate place the permanent plasma chamber of the PDC-GC-III type plasma cleaner of e-commerce Co., Ltd already in Chengdu, and plasma oxidation was handled 2 minutes;
Bonding encapsulation: insert after the cover plate after oxidation processes finished, filter plate, dash receiver are aimed at and clamped in the baking oven 85 ℃ of insulations 40 minutes down, can obtain blood separating mechanism for filtering leucocyte.

Claims (5)

1. blood separating mechanism for filtering leucocyte, it is characterized in that, comprise dash receiver, filter plate and cover plate that stacked successively sealing is installed together, described filter plate adopts SU-8 photoresists material, described cover plate and dash receiver adopt dimethyl silicone polymer (PDMS) material, the lower surface of described cover plate is provided with the transfusion groove, transfusion groove two ends are provided with through hole respectively and draw cover plate, as transfusion inlet and waste liquid outlet, the position that described filter plate is corresponding with described transfusion groove is provided with filter opening, the upper surface of described dash receiver is provided with recycling cavity, and recycling cavity is provided with the transfusion outlet.
2. a kind of blood separating mechanism for filtering leucocyte according to claim 1 is characterized in that, described filter opening is a trough type, and the grooved width is 7-8.5 μ m.
3. a kind of blood separating mechanism for filtering leucocyte according to claim 1 is characterized in that, the outline line of described transfusion groove is the sine curve of symmetry.
4. a kind of blood separating mechanism for filtering leucocyte according to claim 1 is characterized in that, the outline line of described transfusion groove is a snail type curve.
5. the preparation method of a kind of blood separating mechanism for filtering leucocyte according to claim 1 is characterized in that:
Make cover plate and dash receiver: make cover plate and dash receiver mould, the corresponding curing agent with it of dimethyl silicone polymer PDMS is mixed according to 10: 1 weight ratios, cast on the mould, after the extrusion forming, place in the baking oven and toasted 40~50 minutes down at 90~95 ℃, finish curing, the demoulding is stand-by;
Make filter plate: choose the silicon chip that is slightly larger than the filter plate area, the SU-8 photoresists are dripped on silicon chip, then silicon chip is placed on spin coating on the sol evenning machine, formation thickness is the even glue-line about 400um, and carries out first drying and handle; Make the filter opening pattern, and it is printed on the mask plate that transparent film is used as photoetching, adopt the SU-8 photosensitive layer after ultraviolet light is handled first drying to expose, obtain needed filter opening, carry out secondary drying then and handle; Develop at last and rinsing, the filter plate that obtains material and be the SU-8 photoresists is stand-by;
Encapsulation: cover plate, filter plate, the dash receiver made are positioned in the plasma chamber of plasma cleaner, and plasma oxidation was handled 1~2 minute, aimed at then and clamped, insert in the baking oven 80~85 ℃ down insulation got final product in 30~40 minutes.
CN2008100181389A 2008-05-06 2008-05-06 Blood separating mechanism for filtering leucocyte and manufacturing method thereof Expired - Fee Related CN101279200B (en)

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CN111939599B (en) * 2020-07-14 2024-01-12 山东中保康医疗器具有限公司 Method and device for preparing platelet-rich plasma

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