CN104549588B - A kind of multistage microballoon screening chip and using method - Google Patents
A kind of multistage microballoon screening chip and using method Download PDFInfo
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- CN104549588B CN104549588B CN201510025912.9A CN201510025912A CN104549588B CN 104549588 B CN104549588 B CN 104549588B CN 201510025912 A CN201510025912 A CN 201510025912A CN 104549588 B CN104549588 B CN 104549588B
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Abstract
The invention provides a kind of multistage microballoon screening chip and using method, it is primarily of screening unit composition, and one-level screening unit mainly comprises sample holes, 3 sample introduction branched bottoms are respectively communicated with a microballoon screening passage, sample outlet hole, 6 microballoon transport channels, collecting pit, collecting pit outlet vertical cut valves; Present invention also offers the using method of this multistage microballoon screening chip, comprise conventional screening operation, screening of bypassing the immediate leadership operation, interval screening operation.Beneficial effect of the present invention is that the particle diameter uniformity of screening is better, and a slice chip side by side can organize multistage screening unit more, screens simultaneously, or screen different samples simultaneously, improve screening operation efficiency, simply easy to make, use cost is cheap, can batch use of large-scale production.
Description
Technical field
The present invention relates to a kind of novel microballoon screening chip, from use, is the multistage microballoon screening chip of one and using method that use in fields such as material, medical science, bioengineering.
Background technology
At present, along with the development of bioengineering, the treatment of medical science targeted drug, apply microparticle material more and more, simultaneously in material science development, the research and apply of other microparticle material of microstage received is also increasingly extensive.At present, the size selection of microparticle material, mostly also be filter or dry small package method, the method is for the microballoon prepared with use liquid, and it is not very convenient to screen, and particularly easily makes filtration inefficiencies for micron-level particle size, or filtration time is very long; Adopt method for sieving again as microballoon is dried, there are the problems referred to above equally, but also add the oven dry cost of manufacture because of the particulate that exceeds standard.Micro-fluidic chip is the new technology grown up in recent years, for micro droplets particulate, has speed fast, the feature that screening size distribution is low.
Therefore, the micro-fluidic microballoon screening chip of a kind of more professional one and using method is needed, for the screening of micron order particulate in solution.
Summary of the invention
Technical scheme of the present invention is: a kind of multistage microballoon screening chip, it is primarily of screening unit composition, it is characterized in that: first order screening unit is included in a sample holes on chip body one end, sample holes connecting length is the sample introduction main channel of 10mm ~ 15mm, ensures the pipeline pressure of sample introduction liquid.Sample introduction main channel end furcations, separates 3 sample introduction branched bottoms, and every bar sample introduction branched bottom is communicated with the long microballoon screening passage of a 20mm ~ 30mm, and design ensures the carrying out of screening like this.The end of microballoon screening passage is communicated with the sample outlet hole of the long sample output passage of 10mm and sample output passage bottom, and this also for ease of and ensures fully carrying out of screening, required duct length.Have a microballoon transport channel in the both sides of every bar microballoon screening passage, microballoon screening passage is collected microtubule by microballoon and is connected with microballoon transport channel; Article 3, microballoon screening passage totally 6 microballoon transport channels be all parallel to sample output passage, in order to pipeline arrangement and sample the flow direction consistent.Article 6, microballoon transport channel jointly enters an oval collecting pit after the sample outlet hole exceeding sample output passage bottom, is convenient to store microballoon and follow-up pressurized flow.Have a collecting pit passing away in the side, opposite of the microballoon transport channel entrance of collecting pit, collecting pit passing away is connected to collecting pit outlet vertical cut valve.The sample that the design of outlet and stop valve is convenient to screen can be derived from any one-level, is convenient to the flow velocity of sample, the regulation and control of the flow direction simultaneously.More than constitute first order screening unit.
The collecting pit outlet vertical cut valve of first order screening unit is communicated with by interface channel with the injection port vertical cut valve that next stage screens unit, the collecting pit outlet vertical cut valve of the screening unit of next stage is communicated with by interface channel with the injection port vertical cut valve of the screening unit of lower next stage again, by that analogy; Period import and export are all designed with stop valve, and effect is also pressurization in process easy to use or negative pressure, flow velocity, the flow direction of regulation and control sample.The progression of screening unit is the order that flows through according to sample and determines, and sample introduction is the first order, and progression from small to large successively.
Middle every one-level screening unit is except injection port vertical cut valve is different from the first order screening sample holes of unit, the outlet of collecting pit is different from the screening unit of afterbody microballoon transport is portalled, and it is identical that all the other all screen cellular construction with the first order; The import and export of the screening unit of afterbody are that injection port vertical cut valve and microballoon transport are portalled, and it is identical that all the other structures also screen unit with the first order.Except sample introduction main channel, the degree of depth of all passages is equal with the width of sample introduction branched bottom.The batch machining that micro-fluidic chip is convenient in such design is produced.
In technique scheme, described microballoon screening passage, symmetrical chiasma distribution barricade and opposite side barricade on two sidewalls in its microballoon screening chamber, barricade and opposite side barricade are 60 ~ 80 ° towards going out sample prescription to screening with microballoon the opening angle that chamber wall formed, and height and microballoon screen the deep equality of passage.Purpose of design is under certain flow rate, by the laminar fluid of the microballoon screening passage of micro-fluidic chip, can after barricade and opposite side barricade turbulization, microballoon is pooled to the open bottom of each barricade and opposite side barricade, by microballoon collect microtubule screening.Barricade and the distribution of opposite side barricade transpostion interval, spaced distance d between one lateral retaining wall or opposite side barricade is 3 times of the width of sample introduction main channel, the length of barricade and opposite side barricade all ensures that the final position of the inboard termination of barricade and opposite side barricade exceedes the channel centerline in microballoon screening chamber, accounts for 3/5 of microballoon screening chamber width.This design, no matter barricade opening angle is how many, all microballoon can be screened chamber segmentation, overlook and see that microballoon screening chamber is snakelike, its object is also the formation in order to increase turbulent flow, and fluid will screen at microballoon that left and right, chamber is snakelike to be flow through, after barricade and opposite side barricade, form turbulent flow.Microballoon screening each barricade in chamber and the open bottom of opposite side barricade have microballoon collect microtubule, microballoon collect microtubule be connected with the microballoon transport channel that microballoon screens passage both sides, this has designed the screening of microballoon, principle and cross-flow filtration similar.
In technique scheme, the microballoon of described screening unit collects the width of microtubule between 5 μm ~ 500 μm, the width dimensions of the microballoon collection microtubule of 3 microballoon screening passages of every one-level screening unit is consistent, the width dimensions of the microballoon collection microtubule of screening unit at different levels is descending to successively decrease step by step, or except first order screening unit, the width dimensions of the microballoon collection microtubule of screening unit at different levels is consistent.The width of microtubule collected by the microballoon of screening unit 2 ~ 8 specifications, such as: the first order 500 μm, 300 μm, the second level, the third level 100 μm, the fourth stage 80 μm, level V 50 μm, the 6th grade 30 μm, the 7th grade 20 μm, the 8th grade 10 μm; Or the first order 80 μm, 50 μm, the second level, the third level 30 μm, the fourth stage 20 μm, level V 10 μm, the 6th grade 5 μm; Or the first order 10 μm, the second level are 5 μm to the 8th grade.Screening operation is convenient in this design, and the combined sorting that each inter-stage is bypassed the immediate leadership, the facility of particle diameter section screening.The width of the microballoon screening passage of described screening unit at different levels is 2 ~ 2.5 times of the width of sample introduction main channel, the width of sample introduction branched bottom is 4/5 of the width of sample introduction main channel, sample introduction main channel is identical with the width of sample output passage, and the width of microballoon transport channel is that microballoon collects the 2-4 of microtubule width doubly.Design is the flow differential pressure in order to meet each pipeline fluid, screens the modularized design of unit simultaneously, is convenient to the template construct of chip and the batch production of chip.
In technique scheme, described collecting pit outlet vertical cut valve and injection port vertical cut valve are all threeways, can open or close the pipeline of interface channel, or open or close the vertical channel with chip body outside, or close the pipeline of interface channel simultaneously and close the vertical channel with chip body outside.Design is the control manipulation for the ease of screening, and the facility of combination operation that each inter-stage is bypassed the immediate leadership.
Use the using method of a kind of multistage microballoon screening chip of technique scheme, operating procedure is as follows.
Conventional screening operation: first by all collecting pit outlet vertical cut valves and injection port vertical cut valve open-minded with chip body outside, namely lead to air; The liquor sample containing microballoon is added from sample holes, after the collecting pit of first order screening unit has collection sample, the injection port vertical cut valve of unit and the open-minded of chip body outside are screened in collecting pit outlet vertical cut valve and the second level of closing first order screening unit; Open the collecting pit outlet vertical cut valve of first order screening unit and the injection port vertical cut valve of second level screening unit and interface channel, the second level and screen the through of the sample introduction main channel of unit, the first order is screened in unit collecting pit and introduce in second level screening unit through the sample of first time screening; Operation by that analogy.After the afterbody screening sample outlet hole of unit and microballoon transport portal and have sample to flow out, keep sample flow rate, do not screen with resting.
Screening of bypassing the immediate leadership operates: by the first order to the collecting pit outlet vertical cut valve of 3 grades of screening unit at any 1 grade or any 2 grades or the interval of the 6th grade of screening unit, and the 3 grades of injection port vertical cut valves screening unit being screened any 1 grade or any 2 grades or the interval of unit by external capillary and any next stage are connected; Operation screens method of operating routinely, after adding sample from any one-level screening unit, step by step sample solution is introduced next stage screening unit, until after the sample outlet hole microballoon transport of the 8th grade of screening unit portals and have sample outflow, keep sample flow rate, uninterruptedly screen.
Interval screening operation: be connected with outside sampling receiving container by external capillary by the collecting pit outlet vertical cut valve of the second level to the 7th grade of screening unit, accesses by four-way capillary the injection port vertical cut valve that next stage screens unit to respective 3 sample outlet holes that the 7th grade is screened unit by the second level one by one; During operation, first by whole collecting pit outlet vertical cut valves and chip body outside open-minded, close whole interface channel; The second level is through to injection port vertical cut valve and the chip body outside of the 7th grade of screening unit, respective sample introduction main channel; The liquor sample containing microballoon is added from sample holes, have until the collecting pit of first order screening unit and collect after sample, close the open-minded of the collecting pit outlet vertical cut valve of first order screening unit and second level screening unit injection port vertical cut valve and chip body outside; Open the collecting pit outlet vertical cut valve of first order screening unit and the injection port vertical cut valve of second level screening unit and interface channel, the second level and screen the through of the sample introduction main channel of unit, the first order is screened in the collecting pit of unit and introduce in second level screening unit through the sample of first time screening; After the afterbody screening sample outlet hole of unit and microballoon transport portal and have sample to flow out, keep sample flow rate, screen incessantly.
The technology of the present invention feature is easy to make, professional stronger.
Compared with screening microballoon with existing conventional filtration or sieve method, the present invention has following beneficial effect: (1) is professional stronger, can directly and automatic liquid adding device be used in conjunction, the particle diameter uniformity of screening is better; (2) a slice chip side by side can organize multistage screening unit more, screens simultaneously, or the sample that colleague's screening is different, improves screening operation efficiency; (3) simply easy to make, use cost is cheap, can batch use of large-scale production.
Accompanying drawing explanation
Fig. 1 is the microballoon screening chip schematic diagram of a kind of three level screen unit of the present invention.
Fig. 2 is the enlarged diagram of microballoon of the present invention screening passage.
Fig. 3 is the microballoon screening chip schematic diagram of a kind of eight grades of screening unit of the present invention, from top to bottom, is respectively the first order to the 8th grade.
In figure: 1. chip body; 2. sample holes; 3. sample introduction main channel; 4. sample introduction branched bottom; 5. microballoon screening passage; 6. microballoon transport channel; 7. sample output passage; 8. sample outlet hole; 9. collecting pit; 10. collecting pit passing away; 11. collecting pit outlet vertical cut valves; 12. interface channels; 13. injection port vertical cut valves; 14. microballoon transports are portalled; 15. microballoon screening chambeies; Microtubule collected by 16. microballoons; 17. barricades; 18. opposite side barricades.
Detailed description of the invention
Further the present invention is illustrated below in conjunction with drawings and Examples.
Embodiment one:
With reference to Fig. 1, Fig. 2, an a kind of microballoon screening chip having a three level screen unit, the long 10mm in sample introduction main channel 3, wide 1.00mm, dark 1.00mm; Screening unit microballoon screening passage 5 long 20mm, wide be 2.50mm, dark 0.80mm; Barricade 17 and opposite side barricade 18 highly screen passage 5 deep equality with microballoon is 0.80mm; The width of sample introduction branched bottom 4 is 0.80mm, dark 0.80mm; The long 10mm of sample output passage 7, wide 1.00mm, dark 0.80mm; Interface channel 12 width 1.00mm, dark 0.80mm.
The width of the microballoon collection microtubule 16 of first order screening unit is 500 μm, and the width of microballoon transport channel 6 is 1.00mm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 80 °.
The width of the microballoon collection microtubule 16 of second level screening unit is 100 μm, and the width of microballoon transport channel 6 is 0.20mm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 75 °.
The width of the microballoon collection microtubule 16 of third level screening unit is 50 μm, and the width of microballoon transport channel 6 is 0.15mm.The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 65 °.
routine operation:before operation, sample is not more than 0.80mm through pretreatment particle diameter.First by all collecting pit outlet vertical cut valves 11 and injection port vertical cut valve 13 outside open-minded with chip body 1, i.e. logical air.Add the liquor sample containing microballoon from sample holes 2, after waiting for that the collecting pit 9 of the first order has and collects sample, close the open-minded of the collecting pit outlet vertical cut valve 11 of the first order and the injection port vertical cut valve 13 of the second level and chip body 1 outside; Open the through of the injection port vertical cut valve 13 of the collecting pit outlet vertical cut valve 11 of the first order and the second level and the sample introduction main channel 3 of interface channel 12, the second level, introduce in first order collecting pit 9 in second level screening unit through the sample of first time screening.Collect after sample when second level collecting pit 9 has, close the open-minded of the collecting pit outlet vertical cut valve 11 of the second level and the injection port vertical cut valve 13 of the second level and chip body 1 outside; Open the through of the injection port vertical cut valve 13 of the collecting pit outlet vertical cut valve 11 of the second level and the third level and the sample introduction main channel 3 of interface channel 12, the third level, introduce in second level collecting pit 9 in third level screening unit through the sample of twice screening.Operation by that analogy.Until afterbody sample outlet hole 8 and microballoon transport portal 14 have sample to flow out after, keep sample presentation sample flow rate, do not screen with resting.Obtain the microballoon of more than 500 μm, less than 500 μm, less than 100 μm three sections of particle diameters at sample outlet hole 8 at different levels respectively, to portal 14 microballoons obtaining the particle diameter of less than 50 μm in microballoon transport.
Embodiment two:
With reference to Fig. 2, Fig. 3, one has eight grades of a kind of microballoon screening chips screening unit, the long 15mm in sample introduction main channel 3, wide 1.00mm, dark 1.00mm; Screening unit microballoon screening passage 5 long 30mm, wide be 2.50mm, dark 0.80mm; Barricade 17 and opposite side barricade 18 highly screen passage 5 deep equality with microballoon is 0.80mm; The width of sample introduction branched bottom 4 is 0.80mm, dark 0.80mm; The long 10mm of sample output passage 7, wide 1.00mm, dark 0.80mm; Interface channel 12 width 1.00mm, dark 0.80mm.
The width of the microballoon collection microtubule 16 of first order screening unit is 500 μm, and the width of microballoon transport channel 6 is 1.00mm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 80 °.
The width of the microballoon collection microtubule 16 of second level screening unit is 200 μm, and the width of microballoon transport channel 6 is 0.40mm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 70 °.
The width of the microballoon collection microtubule 16 of third level screening unit is 90 μm, and the width of microballoon transport channel 6 is 0.18mm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 60 °.
The width of the microballoon collection microtubule 16 of fourth stage screening unit is 40 μm, and the width of microballoon transport channel 6 is 0.12mm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 60 °.
The width of the microballoon collection microtubule 16 of level V screening unit is 30 μm, and the width of microballoon transport channel 6 is 90 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 60 °.
The width of the microballoon collection microtubule 16 of the 6th grade of screening unit is 20 μm, and the width of microballoon transport channel 6 is 80 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 75 °.
The width of the microballoon collection microtubule 16 of the 7th grade of screening unit is 10 μm, and the width of microballoon transport channel 6 is 40 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 80 °.
The width of the microballoon collection microtubule 16 of the 8th grade of screening unit is 5 μm, and the width of microballoon transport channel 6 is 20 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 80 °.
conventional screening operation: before operation, sample is not more than 0.80mm through pretreatment particle diameter.According to embodiment one method of operating, until after the sample outlet hole 8 of last 8th grade and collecting pit outlet 9 have sample to flow out, keep sample presentation flow velocity, intermittently do not screen.Obtain more than 500 μm, 500 μm and microballoon that is following, less than 200 μm, less than 90 μm, less than 40 μm, less than 30 μm, less than 20 μm, less than 10 μm eight sections of particle diameters respectively at sample outlet hole 8 at different levels, to portal 14 microballoons obtaining the particle diameter of less than 5 μm in microballoon transport.
screening of bypassing the immediate leadership operates:before operation, sample is not more than 0.80mm through pretreatment particle diameter.The collecting pit outlet vertical cut valve 11 of the third level is connected with the injection port vertical cut valve 13 of level V by external capillary; The collecting pit outlet vertical cut valve 11 of level V is connected by the injection port vertical cut valve 13 of external capillary with the 7th grade.Operation screens method of operating routinely, add sample from the injection port vertical cut valve 13 of the third level, step by step sample solution introduced next stage, until the 8th grade of sample outlet hole 8 and microballoon transport portal 14 have sample flow out after, keep sample presentation sample flow rate, uninterruptedly screen.Obtain the microballoon of more than 90 μm, less than 90 μm, less than 30 μm, less than 10 μm four sections of particle diameters at the sample outlet hole 8 of the 3rd, five, seven, eight grade respectively, to portal 14 microballoons obtaining the particle diameter of less than 5 μm in microballoon transport.
Embodiment three:
With reference to Fig. 2, Fig. 3, an a kind of microballoon screening chip having a three level screen unit, the long 15mm in sample introduction main channel 3, wide 1.00mm, dark 0.50mm; Screening unit microballoon screening passage 5 long 30mm, wide be 2.00mm, dark 0.40mm; Barricade 17 and opposite side barricade 18 highly screen passage 5 deep equality with microballoon is 0.40mm; The width of sample introduction branched bottom 4 is 0.40mm, dark 0.40mm; The long 10mm of sample output passage 7, wide 1.00mm, dark 0.40mm; Interface channel 12 width 1.00mm, dark 0.40mm.
The width of the microballoon collection microtubule 16 of first order screening unit is 20 μm, and the width of microballoon transport channel 6 is 0.18mm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 60 °.
The width of the microballoon collection microtubule 16 of second level screening unit is 10 μm, and the width of microballoon transport channel 6 is 0.12mm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 60 °.
The width of the microballoon collection microtubule 16 of third level screening unit is 10 μm, and the width of microballoon transport channel 6 is 90 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 65 °.
The width of the microballoon collection microtubule 16 of fourth stage screening unit is 10 μm, and the width of microballoon transport channel 6 is 80 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 70 °.
The width of the microballoon collection microtubule 16 of level V screening unit is 10 μm, and the width of microballoon transport channel 6 is 40 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 75 °.
The width of the microballoon collection microtubule 16 of the 6th grade of screening unit is 10 μm, and the width of microballoon transport channel 6 is 20 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 75 °.
The width of the microballoon collection microtubule 16 of the 7th grade of screening unit is 10 μm, and the width of microballoon transport channel 6 is 20 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 80 °.
The width of the microballoon collection microtubule 16 of the 8th grade of screening unit is 10 μm, and the width of microballoon transport channel 6 is 20 μm; The opening angle that barricade 17 and opposite side barricade 18 and microballoon screen chamber 15 wall is 80 °.
interval screening operation:before operation, sample is not more than 0.80mm through pretreatment particle diameter.The collecting pit outlet vertical cut valve 11 of the second level to the 7th grade is connected with outside sampling receiving container by external capillary, respective 3 sample outlet holes 8 of the second level to the 7th grade are accessed one by one the injection port vertical cut valve 13 of next stage by four-way capillary, namely 3, second level sample outlet hole 8 is by the injection port vertical cut valve 13 of the four-way capillary access third level, the third level 3 sample outlet holes 8 access the injection port vertical cut valve 13 of the fourth stage by four-way capillary, by that analogy.
During operation, the collecting pit outlet vertical cut valve 11 first by whole is outside open-minded with chip body 1, closes whole interface channel 12.Namely the collecting pit outlet vertical cut valve 11 of the first order leads to outside atmosphere, the second level to the 7th grade of collecting pit outlet vertical cut valve 11 and outside sampling receiving container open-minded.By through for sample introduction main channel 3 outside, respective with chip body 1 for the injection port vertical cut valve 13 of the second level to the 7th grade, namely the injection port vertical cut valve 13 of the second level communicates with air, the four-way capillary that the injection port vertical cut valve 13 of the third level to the 7th grade is connected with upper level sample outlet hole 8 and respective sample introduction main channel 3 through.Add the liquor sample containing microballoon from sample holes 2, after waiting for that the collecting pit 9 of the first order has and collects sample, close the open-minded of the collecting pit outlet vertical cut valve 11 of the first order and second level injection port vertical cut valve 13 and chip body 1 outside; Open the through of the injection port vertical cut valve 13 of the collecting pit outlet vertical cut valve 11 of the first order and the second level and the sample introduction main channel 3 of interface channel 12, the second level, introduce in first order collecting pit 9 in second level screening unit through the sample of first time screening.Until afterbody sample outlet hole 8 and microballoon transport portal 14 have sample to flow out after, keep sample presentation sample flow rate, screen incessantly.The microballoon of more than 20 μm particle diameters is obtained at the sample outlet hole 8 of the second level, in the second level to the 7th grade of collecting pit outlet vertical cut valve 11, to portal 14 microballoons obtaining less than 10 μm particle diameters with the microballoon of the 8th grade transport, obtain the microballoon of 10 μm of ﹤ ﹤, 20 μm of section particle diameters at the sample outlet hole 8 of the 8th grade.
After tested, through 8 grades of screenings, the grain size dispersity of the microballoon that 10 μm of ﹤ ﹤ 20 μm of acquisition are interval is less than 5%.
Illustrate: bypass the immediate leadership operation and interval screening operation, with different chipsets, can combinationally use.If generation channel blockage, utilize sample holes 2, sample outlet hole 8, microballoon to transport to portal the combination of 14, and the threeway effect of collecting pit outlet vertical cut valve 11 and injection port vertical cut valve 13, blocking is washed in anti-phase pressurization open.
Claims (5)
1. a multistage microballoon screening chip, primarily of screening unit composition, it is characterized in that: first order screening unit is included in a sample holes (2) on chip body (1) one end, sample holes (2) connecting length is the sample introduction main channel (3) of 10mm ~ 15mm, sample introduction main channel (3) end furcations, separate 3 sample introduction branched bottoms (4), every bar sample introduction branched bottom (4) is communicated with long microballoon screening passage (5) of a 20mm ~ 30mm, the end of microballoon screening passage (5) is communicated with the sample outlet hole (8) of the long sample output passage (7) of 10mm and sample output passage (7) other end, have a microballoon transport channel (6) in the both sides of every bar microballoon screening passage (5), microballoon screening passage (5) is collected microtubule (16) by microballoon and is connected with microballoon transport channel (6), article 3, microballoon screening passage (5) totally 6 microballoon transport channels (6) be all parallel to sample output passage (7), an oval collecting pit (9) is jointly entered after exceeding the sample outlet hole (8) of sample output passage (7) bottom, have a collecting pit passing away (10) in the side, opposite of microballoon transport channel (6) entrance of collecting pit (9), collecting pit passing away (10) is connected to collecting pit outlet vertical cut valve (11), more than constitute first order screening unit, collecting pit outlet vertical cut valve (11) of first order screening unit is communicated with by interface channel (12) with the injection port vertical cut valve (13) that next stage screens unit, collecting pit outlet vertical cut valve (11) of the screening unit of next stage is communicated with by interface channel (12) with the injection port vertical cut valve (13) of the screening unit of lower next stage again, by that analogy, middle every one-level screening unit transports except portal (14) except injection port vertical cut valve (13) is different from the microballoon that the first order screens the sample holes (2) of unit, the outlet of collecting pit (9) is different from the screening unit of afterbody, and all the other are all identical with the screening cellular construction of the first order, the import and export of the screening unit of afterbody are that injection port vertical cut valve (13) and microballoon transport are portalled (14), and it is identical that all the other structures also screen unit with the first order, except sample introduction main channel (3), the degree of depth of all passages is equal with the width of sample introduction branched bottom (4).
2. the multistage microballoon screening chip of one according to claim 1, it is characterized in that: described microballoon screening passage (5), symmetrical chiasma distribution barricade (17) and opposite side barricade (18) on two sidewalls of its microballoon screening chamber (15), barricade (17) and opposite side barricade (18) are 60 ° ~ 80 ° towards going out sample prescription to screening with microballoon the opening angle that chamber (15) wall formed, and height and microballoon screen the deep equality of passage (5); Barricade (17) and the distribution of opposite side barricade (18) transpostion interval, spaced distance d between one lateral retaining wall (17) or opposite side barricade (18) is 3 times of the width of sample introduction main channel (3), the length of barricade (17) and opposite side barricade (18) all ensures that the final position of the inboard termination of barricade (17) and opposite side barricade (18) exceedes the channel centerline of microballoon screening chamber (15), accounts for 3/5 of microballoon screening chamber (15) width; Have microballoon to collect microtubule (16) at each barricade (17) of microballoon screening chamber (15) and the open bottom of opposite side barricade (18), microballoon is collected microtubule (16) and is connected with the microballoon transport channel (6) that microballoon screens passage (5) both sides.
3. the multistage microballoon screening chip of one according to claim 1, it is characterized in that: the microballoon of described screening unit collects the width of microtubule (16) between 5 μm ~ 500 μm, the width dimensions that microtubule (16) collected by microballoon in 3 microballoons screening passage (5) of every one-level screening unit is consistent, the width dimensions of microballoon collection microtubule (16) of screening unit at different levels is descending to successively decrease step by step, or except first order screening unit, the width dimensions of microballoon collection microtubule (16) of screening unit at different levels is consistent; The width of microballoon collection microtubule (16) of screening unit has 2 ~ 8 specifications; The width of microballoon screening passage (5) of screening unit at different levels is 2 ~ 2.5 times of the width of sample introduction main channel (3), the width of sample introduction branched bottom (4) is 4/5 of the width of sample introduction main channel (3), sample introduction main channel (3) is identical with the width of sample output passage (7), and the width of microballoon transport channel (6) is 2 ~ 4 times that microtubule (16) width collected by microballoon.
4. the multistage microballoon screening chip of one according to claim 1, it is characterized in that: described collecting pit outlet vertical cut valve (11) and injection port vertical cut valve (13) are all threeways, can open or close the pipeline of interface channel (12), or open or close the vertical channel outside with chip body (1), or close the pipeline of interface channel (12) simultaneously and close the vertical channel outside with chip body (1).
5. use the method for a kind of multistage microballoon screening chip described in any one of claim 1-4, it is characterized in that, operating procedure is as follows:
Conventional screening operation: first by all collecting pit outlet vertical cut valve (11) and injection port vertical cut valve (13) outside open-minded with chip body (1), namely lead to air; The liquor sample containing microballoon is added from sample holes (2), after the collecting pit (9) of first order screening unit has collection sample, the injection port vertical cut valve (13) of unit and the open-minded of chip body (1) outside are screened in collecting pit outlet vertical cut valve (11) and the second level of closing first order screening unit; The injection port vertical cut valve (13) of collecting pit outlet vertical cut valve (11) and second level screening unit of opening first order screening unit screens the through of the sample introduction main channel (3) of unit with interface channel (12), the second level, the first order is screened in the collecting pit (9) of unit and introduces in second level screening unit through the sample of first time screening; Operation by that analogy; Portal after (14) have sample to flow out until the afterbody screening sample outlet hole (8) of unit and microballoon transport, maintenance sample flow rate, does not screen with resting;
Screening of bypassing the immediate leadership operates: one has eight grades of chips screening unit, the first order is screened collecting pit outlet vertical cut valve (11) of unit to the screening unit of 3 grades at any 1 grade or any 2 grades or the interval of the 6th grade of screening unit, the injection port vertical cut valve (13) being screened the screening unit of 3 grades at any 1 grade or any 2 grades or the interval of unit by external capillary and any next stage is connected; Operation screens method of operating routinely, after adding sample from any one-level screening unit, step by step sample solution is introduced next stage screening unit, after until sample outlet hole (8) the microballoon transport of the 8th grade of screening unit is portalled, (14) have sample to flow out, keep sample flow rate, uninterruptedly screen;
Interval screening operation: one has eight grades of chips screening unit, the second level is screened unit to be connected with outside sampling receiving container by external capillary to collecting pit outlet vertical cut valve (11) that the 7th grade is screened unit, the second level is screened respective 3 sample outlet holes (8) of unit to the 7th grade of screening unit access next stage screening unit one by one injection port vertical cut valve (13) by four-way capillary; During operation, first by outside open-minded to whole collecting pit outlet vertical cut valve (11) and chip body (1), close whole interface channel (12); The second level is through to the sample introduction main channel (3) that the injection port vertical cut valve (13) of the 7th grade of screening unit is outside, respective with chip body (1); The liquor sample containing microballoon is added from sample holes (2), have until the collecting pit (9) of first order screening unit and collect after sample, close the open-minded of collecting pit outlet vertical cut valve (11) of first order screening unit and second level screening unit injection port vertical cut valve (13) and chip body (1) outside; The injection port vertical cut valve (13) of collecting pit outlet vertical cut valve (11) and second level screening unit of opening first order screening unit screens the through of the sample introduction main channel (3) of unit with interface channel (12), the second level, the first order is screened in the collecting pit (9) of unit and introduces in second level screening unit through the sample of first time screening; Portal after (14) have sample to flow out until the afterbody screening sample outlet hole (8) of unit and microballoon transport, maintenance sample flow rate, screens incessantly.
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| CN109682962B (en) * | 2019-01-15 | 2024-02-23 | 中南大学 | Immunofluorescence detection system and detection method based on microfluidic chip |
| CN111282604B (en) * | 2020-02-12 | 2022-01-04 | 赛纳生物科技(北京)有限公司 | Method for entering biochemical chip microspheres |
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| CN102896006B (en) * | 2012-10-09 | 2015-04-08 | 中国科学院半导体研究所 | Microsphere separation and screening chip and preparation method thereof |
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