CN104588139B - A kind of micro-fluidic chip and using method preparing microballoon - Google Patents
A kind of micro-fluidic chip and using method preparing microballoon Download PDFInfo
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Abstract
The invention provides a kind of micro-fluidic chip and the using method of preparing microballoon, it is primarily of chip body, cooled wafer and volatilization exhaust chip are composited, it is characterized in that including overall two bar V-type mixing ducts one in U-shaped and two bar V-type mixing duct two, the double-U-shaped pipeline of rounded cooling, and in the cooling sizing collecting pit of double-U-shaped pipeline side and outlet etc.Invention additionally provides the use method of operating of chip.Beneficial effect of the present invention is that the grain size decentralization of the microballoon of preparation is little, and dimensional accuracy is high, and can prepare rapidly the complex microsphere containing two or more composition, the efficiency of production is high, simply easy to operate.
Description
Technical field
The present invention relates to a kind of chip of novel manufacture liquid microballoon, from use, is a kind of micro-fluidic chip and the using method preparing microballoon used in a kind of materialogy, bioengineering, field of medicaments.
Background technology
At present, the investigation and application that micro-composite particles of receiving uses in materialogy, bioengineering, field of medicaments is more and more general, conventional sol-gel process preparation liquid state or solid particle, more and more universal.But the method operation has certain difficulty, and uniformity, the reappearance of preparation process are more bad.The development of microfluidic chip technology, for sol-gel process preparation is liquid or solid particle brings a kind of new techniques and methods.The method production efficiency is high, and Microsphere Size controls easily, simple to operate, more and more welcome.But micro-fluidic chip lacks the comparatively general chip preparing particulate.The micro-fluidic chip of the making particulate of some design, structure is comparatively complicated, adds cost of manufacture and use cost, is difficult to promote the use of.
Therefore, need a kind of more professional, comparatively general micro-fluidic chip preparing microballoon and its using method, for receiving the preparation of micro-composite particulate material.
Summary of the invention
Technical scheme of the present invention is: a kind of micro-fluidic chip preparing microballoon, it is characterized in that: be processed with a sample holes A and sample holes B in a corner of rectangular chip body, the flat tube of the 10mm length that sample holes A connects is parallel to the long limit of chip body, the flat tube of the 10mm length that sample holes B connects is parallel to the minor face of chip body, and two pipelines vertically meet at T-shaped pipeline mixing mouth one mutually.Or be processed with a sample holes A, a sample holes B and sample holes D, the flat tube that the 10mm connected separately is long, 3 pipelines meet at T-shaped pipeline mixing mouth one.Design principle is according to the common method of the microchannel formation drop of micro-fluidic chip.Passage length, for the viscosity preparing material microballoon, ensures the pressure differential of fluid.Pipeline after crossing is being parallel to the long limit of chip body, is still keeping the straight of 20mm length, and object is also the pressure differential ensureing fluid.Pipeline after crossing turns round to the long limit of chip body opposite side, connect be parallel to the long limit of chip body, two bar V-type mixing ducts one in U-shaped; V-type passage is the abundant mixing ensureing balling-up drop internal composition.
At the end of two bar V-type mixing ducts one of chip body opposite side long edge position, connect a wall scroll V-type mixing duct perpendicular to the long limit of chip body, the other end of wall scroll V-type mixing duct is in the side, chip body long limit at sample holes A and sample holes B place.The object adopting wall scroll V-type mixing duct to connect also is the abundant mixing for strengthening balling-up drop internal composition.
Wall scroll V-type mixing duct connects a straight passage subsequently, and this is straight passage is towards another termination of chip body corresponding to a sample hole A and sample holes B; Be processed with sample holes C in the place of the side 10mm of straight passage, and the flat tube that the 10mm that straight passage is connected with sample holes C grows is mutually vertical, and is intersected in T-shaped pipeline mixing mouth two.This design, be design for increasing the second mixed liquor, manufacture complex microsphere, its composition is often made up of two or more.Pipeline after crossing be parallel to the long limit of chip body, still keep 20mm long straight after, length ensures the pressure differential of flow velocity.
Pipeline after crossing turn round connect perpendicular to the long limit of chip body, two bar V-type mixing ducts two in U-shaped; Two bar V-type mixing duct two connects a rounded double-U-shaped pipeline of cooling.The length of this design in order to increase cooling duct, and be convenient to outside enforcement of concentrating cooling.
Cool the straight channel of double-U-shaped pipe outlet by a long limit of vertical chip body, communicate with at the sizing collecting pit cooling double-U-shaped pipeline side, sizing collecting pit just has the outlet on an exit passageway connection chip body to straight channel import department.This design, make semi liquid state microballoon, through heating, cooling curing, and removes volatile matter further, solidifying and setting.
In technique scheme, the V word opening angle of described V-type mixing duct is 30 ° ~ 60 °, and connection undulate alternately put upside down in length of side 3-5mm, V word.Be designed to increase the rapidly mixed of microballoon at turning, guarantee flow velocity is unlikely to reduce too much.Two bar V-type mixing duct two, the chip carrier below the chip body of its region is pasted with rectangular heating plate.The design of heating plate is to allow the complex microsphere of some composition, can after accelerate mixing and crosslinked.The double-U-shaped pipeline of described cooling, the airtight cooled wafer being bonded with a rectangle above the chip body of its region, cooled wafer is concave, and forms a cold water storage chamber between chip body; On the surface of cooled wafer, processing is provided with cooling water inlet/outlet pipe; Below the cold water storage chamber of cooled wafer, cool the surface of the chip body of double-U-shaped pipeline region, being processed with the reverse frustoconic cooling pit that tmm is dark, the degree of depth t of cooling pit, with chip body cooling the thickness T on double-U-shaped pipeline, having t=1/2 ~ 3/4Tmm.The design of cooled wafer is that the microballoon in order to make heating reflect rapidly is excessively cold, finalizes the design almost.The requirement of the depth dimensions of cooling pit, should expand cooling effect, can not get through chip body surface again.
In technique scheme, described sizing collecting pit, the airtight volatilization exhaust chip being bonded with a rectangle above the chip body of its region.This design is further solvent flashing, sizing and solidifying microballoon.Volatilization exhaust chip is concave, and forms an exhaust cavity between chip body; On the surface of volatilization exhaust chip, rectangle both sides respectively process and are provided with 5-10 breather pipe.Breather pipe is used for blowing to exhaust cavity, increases the air flowing of exhaust cavity, accelerates volatilization volatile solvent.Remaining surface is processed with the volatilization steam vent of more than 20 side by side, and object is also be beneficial to exhaust to take away volatile substance.Below the exhaust cavity of volatilization exhaust chip, the chip body surface of sizing collecting pit region, processing is provided with sizing collecting pit blast pipe and is communicated with sizing collecting pit.Sizing collecting pit blast pipe stretches out the height d on chip body surface, with the height H of exhaust cavity, and d=1/2Hmm.The object of the design d height of sizing collecting pit blast pipe, be to make the microballoon of sizing collecting pit have the inside that can not flow into exhaust cavity under flowing pressure, ensure again in air blowing situation, the certain flow rate pressure that gas produces can not directly have influence in sizing collecting pit.Stretch out Tai Gao be not easy to again air flowing and volatilization and be vented.
In technique scheme, additionally provide a kind of using method preparing the micro-fluidic chip of microballoon, its operating procedure is as follows:
The technology of the present invention feature is easy to operate, professional stronger.
Compared with preparing microballoon with existing conventional method, the present invention has following beneficial effect: the grain size decentralization of microballoon prepared by (1) is little, and dimensional accuracy is high; (2) a slice can prepare rapidly the complex microsphere containing two or more composition, improves the efficiency that microballoon is produced; (3) simply easy to operate, use cost is cheap.
Accompanying drawing explanation
Fig. 1 is the chip plan structure schematic diagram of a kind of 3 injection ports of the present invention.
Fig. 2 is that sizing collecting pit of the present invention is vented the enlarged diagram of chip with volatilization.
Fig. 3 is that sizing collecting pit of the present invention is vented the schematic diagram of the A-A view of chip with volatilization.
Fig. 4 is the enlarged diagram of the double-U-shaped pipeline of cooling of the present invention and cooled wafer.
Fig. 5 is the schematic diagram of the A-A view of the double-U-shaped pipeline of cooling of the present invention and cooled wafer.
Fig. 6 is the chip plan structure schematic diagram for a kind of 4 injection ports of the present invention of the present invention.
In figure: 1. chip body; 2. pair bar V-type mixing duct one; 3. sample holes A; 4.T shape pipeline mixing mouth one; 5. sample holes B; 6. composite pellets; 7. sample holes C; 8.T shape pipeline mixing mouth two; 9. pair bar V-type mixing duct two; 10. heating plate; The double-U-shaped pipeline of 11. cooling; 12. cooled wafers; 13. cooling water inlet/outlet pipes; 14. volatilization exhaust chips; 15. outlets; 16. sizing collecting pits; 17. breather pipes; 18. volatilization steam vents; 19. sizing collecting pit blast pipes; 20. exhaust cavities; 21. cooling pits; 22. cold water storage chambers.
Detailed description of the invention
Further the present invention is illustrated below in conjunction with drawings and Examples.
Embodiment one:
Referring to figs. 1 through the shape and structure in Fig. 5, a kind of micro-fluidic chip preparing microballoon, has a sample holes A3, a sample holes B5 and sample holes C7.The V word opening angle of V-type mixing duct is 30 °, length of side 3mm.The whole channel width of chip 500 μm, dark 300 μm.The cold water storage chamber 22 height 3mm of cooled wafer 12; Cool the thickness T=3mm on double-U-shaped pipeline 11, cooling pit 21 degree of depth t=2mm.On the surface of volatilization exhaust chip 14, rectangle both sides respectively process and are provided with 5 breather pipes 17, and remaining surface is processed with 100 volatilization steam vents 18 side by side; The exhaust cavity 20 height H=3mm of volatilization exhaust chip 14, sizing collecting pit blast pipe 19 stretches out the height d=1.5mm on chip body 1 surface.
During operation, get out polyvinyl butyral resin (PVB) the carrene organic solution being dispersed with hydroxyapatite of 1%, as oil phase one.Get out the deionized water solution being dissolved with polyethylene of dispersing agent alcohol, as aqueous phase.Get out to be dispersed with PLA (PLA) the carrene organic solution of 0.5% of nanometer iron powder, as oil phase two.
Connect the cooling water inlet/outlet pipe 13 of cooled wafer 12, mixed for frozen water 0 DEG C of deionized water infusion is entered cold water storage chamber 22, keeps circulating.The reversal connection of pumping cycle pump is connected tubule, then receives on each breather pipe 17 on volatilization exhaust chip 14 with point head tube and polyethylene capillary soft tube; Start pumping cycle pump, keep blowing to exhaust cavity 20.Open heating plate 10 power supply, adjustment temperature is 30 DEG C.
Deionized water solution is added from sample holes A3 with the note speed of 10 μm/S with syringe pump.When deionized water solution fills sizing collecting pit 16 after outlet 15 outflow, add PVB carrene organic solution from sample holes B5 with the note speed of 5 μm/S with syringe pump.Now can form composite pellets 6 at T-shaped pipeline mixing mouth 1.After bead flows through wall scroll V-type mixing duct, PLA carrene organic solution syringe pump is added from sample holes C7 with the note speed of 5 μm/S.Due to oil phase one and the affinity interaction of oil phase two, now composite pellets 6 can be formed in T-shaped pipeline mixing mouth 28 second time.Composite pellets 6 mixes further through two bar V-type mixing duct 9, enters the double-U-shaped pipeline 11 of cooling and solidifies.Then store at sizing collecting pit 16, get rid of carrene organic matter, further sizing and solidifying.Finally, the hydroxyapatite-iron powder-PVB – PLA complex microsphere prepared is collected from outlet 15.After testing, microballoon is oval, and average grain diameter is mainly at about=400 μm.
Embodiment two:
Referring to figs. 1 through the shape and structure in Fig. 5, a kind of micro-fluidic chip preparing microballoon, the V word opening angle of V-type mixing duct is 60 °, length of side 5mm.The whole channel width of chip 100 μm, dark 100 μm.The cold water storage chamber 22 height 2mm of cooled wafer 12; Cool the thickness T=2mm on double-U-shaped pipeline 11, cooling pit 21 degree of depth t=1mm.On the surface of volatilization exhaust chip 14, rectangle both sides respectively process and are provided with 10 breather pipes 17, and remaining surface is processed with 50 volatilization steam vents 18 side by side; The exhaust cavity 20 height H=2mm of volatilization exhaust chip 14, sizing collecting pit blast pipe 19 stretches out the height d=1mm on chip body 1 surface.
Method of operating, according to embodiment one, obtains circular microballoon.After testing, microspherulite diameter is mainly between=80 μm-90 μm.
Embodiment three:
With reference to the shape and structure in Fig. 2 to Fig. 6, a kind of micro-fluidic chip preparing microballoon, has a sample holes A3, sample holes B5, a sample holes D and sample holes C7.The V word opening angle of V-type mixing duct is 45 °, length of side 4mm.The whole channel width of chip 80 μm, dark 50 μm.The cold water storage chamber 22 height 4mm of cooled wafer 12; Cool the thickness T=4mm on double-U-shaped pipeline 11, cooling pit 21 degree of depth t=3mm.On the surface of volatilization exhaust chip 14, rectangle both sides respectively process and are provided with 8 breather pipes 17, and remaining surface is processed with 25 volatilization steam vents 18 side by side; The exhaust cavity 20 height H=4mm of volatilization exhaust chip 14, sizing collecting pit blast pipe 19 stretches out the height d=2mm on chip body 1 surface.
Method of operating, according to embodiment one, sample holes A3 and sample holes B5 adds the oil phase of 2 kinds of compositions, and sample holes D adds aqueous phase, and sample holes C7 adds the crosslinked crosslinking agent glyoxal of 2 kinds of oil-phase components, obtains circular microballoon.After testing, microsphere average grain diameter is mainly at=50 μm.
Claims (4)
1. prepare the micro-fluidic chip of microballoon for one kind, it is primarily of chip body (1), cooled wafer (12) and volatilization exhaust chip (14) are composited, it is characterized in that: be processed with a sample holes A(3 in a corner of rectangular chip body (1)) and a sample holes B(5), sample holes A(3) the long flat tube of the 10mm that connects is parallel to the long limit of chip body (1), sample holes B(5) the long flat tube of the 10mm that connects is parallel to the minor face of chip body (1), and two pipelines vertically meet at T-shaped pipeline mixing mouth one (4) mutually; Or be processed with a sample holes A(3), a sample holes B(5) an and sample holes D, the flat tube that the 10mm connected separately is long, 3 pipelines meet at T-shaped pipeline mixing mouth one (4); Pipeline after crossing be parallel to the long limit of chip body (1), still keep 20mm long straight after, turning round in the long limit to chip body (1) opposite side, connects and be parallel to chip body (1) long limit, overall two bar V-type mixing ducts one (2) in U-shaped; At the end of two bar V-type mixing ducts one (2) of chip body (1) opposite side long edge position, connect a wall scroll V-type mixing duct perpendicular to chip body (1) long limit, the other end of wall scroll V-type mixing duct is at sample holes A(3) and sample holes B(5) side, chip body (1) long limit at place; Wall scroll V-type mixing duct connects a straight passage subsequently, and this is straight passage is towards sample hole A(3) and a sample holes B(5) another termination of corresponding chip body (1); Sample holes C(7 is processed with) in the place of the side 10mm of straight passage, and straight passage and sample holes C(7) the long flat tube of the 10mm that is connected is mutually vertical, and be intersected in T-shaped pipeline mixing mouth two (8), pipeline after crossing be parallel to the long limit of chip body (1), still keep 20mm long straight after, turn round and connect perpendicular to chip body (1) long limit, overall two bar V-type mixing ducts two (9) in U-shaped; Two bar V-type mixing duct two (9) connects a rounded double-U-shaped pipeline of cooling (11), cool the straight channel of double-U-shaped pipeline (11) outlet by a long limit of vertical chip body (1), communicate with at the sizing collecting pit (16) cooling double-U-shaped pipeline (11) side, sizing collecting pit (16) just has the outlet (15) on exit passageway connection chip body (1) to straight channel import department.
2. a kind of micro-fluidic chip preparing microballoon according to claim 1, is characterized in that: the V word opening angle of described V-type mixing duct is 30 ° ~ 60 °, and connection undulate alternately put upside down in length of side 3-5mm, V word; Two bar V-type mixing duct two (9), the chip carrier of chip body (1) below in its region is pasted with rectangular heating plate; The double-U-shaped pipeline of described cooling (11), the airtight cooled wafer (12) being bonded with a rectangle in chip body (1) top in its region, cooled wafer (12) in concave, and forms a cold water storage chamber (22) between chip body (1); On the surface of cooled wafer (12), processing is provided with cooling water inlet/outlet pipe (13); Below the cold water storage chamber (22) of cooled wafer (12), cool the surface of the chip body (1) of double-U-shaped pipeline (11) region, be processed with the reverse frustoconic cooling pit (21) that tmm is dark, the degree of depth t of cooling pit (21), with chip body (1) cooling the thickness T on double-U-shaped pipeline (11), there is t=1/2 ~ 3/4Tmm.
3. a kind of micro-fluidic chip preparing microballoon according to claim 1, it is characterized in that: described sizing collecting pit (16), airtight volatilization exhaust chip (14) being bonded with a rectangle in chip body (1) top in its region, volatilization exhaust chip (14) in concave, and forms an exhaust cavity (20) between chip body (1); On the surface of volatilization exhaust chip (14), rectangle both sides respectively process and are provided with 5-10 breather pipe (17), and remaining surface is processed with the volatilization steam vent (18) of more than 20 side by side; Volatilization exhaust chip (14) exhaust cavity (20) below, sizing collecting pit (16) region chip body (1) surface, processing be provided with sizing collecting pit blast pipe (19) be communicated with sizing collecting pit (16); The height d on chip body (1) surface is stretched out in sizing collecting pit blast pipe (19), with the height H of exhaust cavity (20), and d=1/2Hmm.
4. a kind of using method preparing the micro-fluidic chip of microballoon according to any one of claim 1-3, it is characterized in that, operating procedure is as follows:
Connect the cooling water inlet/outlet pipe (13) of cooled wafer (12), mixed for frozen water 0 DEG C of deionized water infusion is entered cold water storage chamber (22), keeps circulating; The reversal connection of pumping cycle pump is connected tubule, then receives on each breather pipe (17) in volatilization exhaust chip (14) with point head tube and polyethylene capillary soft tube; Start pumping cycle pump, keep blowing to exhaust cavity (20); Open heating plate (10) power supply, adjust required temperature;
With syringe pump from sample holes A(3) add aqueous phase, when aqueous phase fills sizing collecting pit (16) after outlet (15) outflow, with syringe pump from sample holes B(5) add oil phase one reagent; After the microballoon formed flows through wall scroll V-type mixing duct, by oil phase two from sample holes C(7) add, finally, collect the complex microsphere prepared from outlet 15;
Or according to said method, sample holes A(3) and sample holes B(5) add the oil phase of 2 kinds of compositions, sample holes D adds aqueous phase, sample holes C(7) add the crosslinked crosslinking agent of 2 kinds of oil-phase components, obtain complex microsphere.
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| CN109655447B (en) * | 2019-01-28 | 2022-04-08 | 广东海天创新技术有限公司 | Detection system and method for microbial enumeration |
| CN110585476B (en) * | 2019-08-02 | 2022-05-17 | 南方科技大学 | Preparation method of non-spherical hydrogel microparticle embolic agent |
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