CN102671730A - Polymeric microfluidic chip integrating nickel column microarrays and preparation method thereof - Google Patents
Polymeric microfluidic chip integrating nickel column microarrays and preparation method thereof Download PDFInfo
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- CN102671730A CN102671730A CN2012101590581A CN201210159058A CN102671730A CN 102671730 A CN102671730 A CN 102671730A CN 2012101590581 A CN2012101590581 A CN 2012101590581A CN 201210159058 A CN201210159058 A CN 201210159058A CN 102671730 A CN102671730 A CN 102671730A
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Abstract
The invention discloses a polymeric microfluidic chip integrating nickel column microarrays and a preparation method thereof. The polymeric microfluidic chip disclosed by the invention comprises a glass substrate, an electrode on the glass substrate, the nickel column microarrays on the electrode and a chip substrate provided with a microchannel, wherein the chip substrate is fixedly arranged on the glass substrate; and the electrode and the nickel column microarrays are positioned in the microchannel of the chip substrate. The method disclosed by the invention comprises the steps of preparing the electrode on the glass substrate, preparing the nickel column microarrays on the electrode, preparing the polymeric microfluidic chip substrate provided with the microchannel, and bonding the glass substrate with the chip substrate. The microfluidic chip disclosed by the invention has the advantages that magnetic particles can be separated and released in a controllable manner, the separation efficiency is high and the magnetic particles are easy to release, so the microfluidic chip has a good application prospect in the field of cell research. The method disclosed by the invention has the advantages that the integration of the nickel column microarrays in the microfluidic chip is realized, the process is simple and the cost is low, so the method is suitable for industrial production.
Description
Technical field
The invention belongs to the micro-total analysis system field, polymeric micro-fluidic chip of particularly a kind of integrated nickel post microarray and preparation method thereof.
Background technology
The micro-fluidic chip technique functions comes from the nineties in 20th century, is applied to the analytical chemistry field at first, and it is architectural feature with the microchannel; With life science is main research object, through micro-electromechanical processing technology (MEMS), whole breadboard function is comprised that print preliminary treatment, reaction, separation, detection etc. are integrated on the chip of a micro-meter scale; Analysis speed is greatly improved, has the integrated level height, reagent consumption is few; Cost of manufacture is low, characteristics such as analysis efficiency height.Magnetic-particle since its intrinsic property and with the crosslinkable property of cell, controlling of magnetic-particle had very big application potential in cell research.
Control in the technology based on the magnetic-particle of micro-fluidic chip at present; Be employed in mainly that chip applies or remove the method for external magnetic field outward or the method for integrated electromagnet in chip; The former directly controls the magnetic-particle in the chip channel in chip exterior with permanent magnet; Though this method is simple,, be difficult under minute yardstick, accurately control along with the quick decay of magnetic field in passage; The latter is with micro-machined method less electromagnet of integrated volume outside chip channel; To realize under the minute yardstick to the controlling of magnetic-particle, though this method integrated level is high, the process complicacy; And the Joule heat that on electromagnet, produces is difficult to disperse, to such an extent as to burn out circuit.
Summary of the invention
The objective of the invention is to the problem that prior art exists provide that a kind of cost is low, the polymeric micro-fluidic chip of the integrated nickel post microarray that do not produce Joule heat and preparation method thereof.
For achieving the above object, the present invention adopts following technical scheme:
One, a kind of polymeric micro-fluidic chip of integrated nickel post microarray; This chip comprises: the electrode on glass substrate, the glass-chip, the nickel post microarray on the electrode and have the chip substrate of microchannel; Described chip substrate is fixed on the glass substrate, and described electrode and described nickel post microarray are arranged in the microchannel of described chip substrate.
Above-mentioned nickel post is cylindrical, and it highly is 10 μ m, and diameter is 30 μ m.
Above-mentioned electrode is a cr-au electrode, and thickness is 50-100nm.
Two, the preparation method of above-mentioned polymeric micro-fluidic chip comprises step:
1, on glass substrate, prepares electrode, and on electrode, prepare nickel post microarray;
2, preparation has the polymeric micro-fluidic chip substrate of microchannel, and described chip substrate adopts dimethyl silicone polymer (PDMS) to prepare;
3, step 1 gained glass substrate and step 3 gained chip substrate are carried out bonding, promptly obtain the polymeric micro-fluidic chip of integrated nickel post microarray.
The process that on glass substrate, prepares electrode in the step 1 is specially:
Adopt soft etching method that electrode pattern is transferred on the glass substrate, adopt vapour deposition method or magnetron sputtering method on the electrode pattern on the glass substrate, to prepare electrode then.
Above-mentioned electrode is a cr-au electrode, and its thickness is 50-100nm.
The process that on electrode, prepares nickel post microarray in the step 1 is specially:
Adopt soft etching method with the microarray design transfer to electrode, at the microarray pattern of the electrode metal plated nickel that powers on, promptly obtain nickel post microarray then.
Above-mentioned nickel post is cylindrical, and it highly is that 10 μ m, diameter are 30 μ m.
Adopt soft etching method or reactive ion etching legal system to be equipped with the formpiston template of polymer fluidic chip, liquid dimethyl silicone polymer is poured on the formpiston template, after the curing,, promptly obtain having the chip substrate of microchannel through the demoulding.
Above-mentioned formpiston template is the silicon mold template.
When external magnetic field that the prepared micro-fluidic chip of this method is applied, the single nickel post that is integrated on the micro-fluidic chip produces strong induced magnetic field gradient around all, through regulating the size of external magnetic field, thus the size of indirect regulation induced magnetic field gradient.When having the induced magnetic field gradient around the nickel post; The magnetic-particle that flows through the nickel post can be adsorbed onto on the nickel post by the magnetic field force effect; When the induced magnetic field gradient disappeared, magnetic-particle can be washed away by flowing fluid again, thereby had realized magnetic-particle is realized controlled catch and discharging.The prepared micro-fluidic chip of this method can be widely used in controlling and screening of cell; For example; Can be through in the surface-crosslinked different biomolecule of magnetic-particle (protein, polypeptide etc.), the micro-fluidic chip that this method is prepared is used for that circulating tumor cell, erythroblast are isocellular catches and discharge.
Compared with prior art, the present invention has the following advantages and beneficial effect:
1, the inventive method has realized integrated in micro-fluidic chip of nickel post microarray, and process is simple, and cost is low, is suitable for suitability for industrialized production;
2, micro-fluidic chip of the present invention can be realized controlled catch and discharging to magnetic-particle, has higher capture rate, and is prone to discharge; And this chip in when work owing to there is not electric current to get into, therefore do not have Joule heat and produce.
Description of drawings
Fig. 1 is the whole vertical view of micro-fluidic chip of the present invention;
Fig. 2 is the vertical section sketch map of vapor deposition glass substrate that cr-au electrode is arranged;
The vertical section sketch map of the glass substrate of Fig. 3 is integrated nickel post microarray;
Fig. 4 is the vertical section sketch map of silicon mold template;
Fig. 5 has been down the vertical section sketch map of the formpiston template of dimethyl silicone polymer;
Fig. 6 is the A-A cutaway view among Fig. 1;
Fig. 7 is that nickel post microarray among Fig. 1 is at the design sketch of microscopically;
Fig. 8 is the effect figure that micro-fluidic chip of the present invention is caught magnetic-particle;
Fig. 9 is the effect figure that micro-fluidic chip of the present invention discharges magnetic-particle.
Among the figure: 1-glass substrate, 2-polymeric micro-fluidic chip substrate, 3-electrode, 4-nickel post microarray, 5-monocrystalline silicon piece, 6-SU8-2050 model photoresist, 7-injection port, 8-outlet.
The specific embodiment
Fig. 1 is the vertical view of the polymeric micro-fluidic chip of the integrated nickel post of the present invention microarray, and Fig. 6 is the A-A cutaway view among Fig. 1, as can be seen from the figure; Electrode 3 is on glass substrate 1; Nickel post microarray 4 is on electrode, and the design sketch at microscopically of nickel post microarray 4 is as shown in Figure 7, and polymeric micro-fluidic chip substrate 2 has microchannel 5; Electrode 3 is arranged in microchannel 5 with nickel post microarray 4, and injection port 7 is used for respectively feeding and the pass-out magnetic-particle with outlet 8.
Be further described below with reference to the accompanying drawing specific embodiments of the invention:
The preparation method of the polymeric micro-fluidic chip of a kind of integrated nickel post microarray that the present invention proposes comprises step:
1, on glass substrate, prepares electrode, and on electrode, prepare nickel post microarray
This step further comprises following substep:
1) adopt soft etching method that electrode pattern is transferred on the glass substrate; This substep is specially: on the washed glass substrate, coat the AZ-5214 photoresist; Cover the one side that scribbles photoresist at glass substrate to the mask that is printed on electrode pattern then, wherein, electrode pattern is the rectangle of long 5mm, wide 500 μ m; Place under the ultraviolet light exposure after 250 seconds glass substrate; The glass substrate that finishes exposure is put in the AZ photoresist developing liquid and was developed 40 seconds, take out rinse well and dry up with deionized water after, promptly obtain having the glass substrate of electrode pattern
2) adopt vapour deposition method on the electrode pattern of glass substrate, to prepare electrode; Prepared electrode is a cr-au electrode in this practical implementation; This substep is specially: the glass substrate that will have electrode pattern placed vacuum coating equipment vapor deposition chromium billon 3 hours; Dissolve the remaining photoresist of glass substrate surface with acetone soln then, promptly on glass substrate, obtain the cr-au electrode of long 5mm, wide 500 μ m, thick 50-100nm.Fig. 2 has the schematic cross section of the glass substrate of cr-au electrode for vapor deposition.
Above-mentionedly also can adopt magnetron sputtering method of the prior art to prepare electrode, not do at this and give unnecessary details.
3) adopt soft etching method that the microarray pattern is moved on on the cr-au electrode; This substep is specially: have the one side of electrode to coat the AZ-4620 photoresist on the glass substrate; Comprise also being coated with the last layer photoresist on the electrode, the mask that will be printed on the microarray pattern then covers the one side that scribbles photoresist at glass substrate, and makes microarray pattern and electrode alignment; Glass substrate is placed under the ultraviolet light exposure 380 seconds; The glass substrate that finishes exposure is put in the AZ photoresist developing liquid and was developed 4 minutes, take out rinse well and dry up with deionized water after, be about to the microarray design transfer to electrode.Microarray pattern in this practical implementation is a circle evenly distributed, diameter 30 μ m.
4) at the microarray pattern of the cr-au electrode metal plated nickel that powers on, promptly obtain nickel post microarray, this substep is specially: glass substrate and nickel sheet are placed electrolyte; The negative electrode of one direct current power supply is linked to each other with cr-au electrode; Anode connects the nickel sheet, and the setting electroplating current is 0.03A, after electroplating 3 minutes; Taking-up dissolves the remaining photoresist of glass substrate surface with acetone soln; After rinsing well and dry up with deionized water, promptly on the microarray pattern, prepare height 10 μ m, diameter 30 μ m, columned nickel post microarray, Fig. 7 is the design sketch of nickel post microarray at microscopically.At the electrolyte that this step adopted is with 300 gram nickel sulfate hexahydrate (NiSO
46H
2O), 35 grams, six water nickel chloride (NiCl6H
2O), 40 gram boric acid (H
3BO
3), 0.04 gram lauryl sodium sulfate (NaC
12H
25O
4S), 2 gram asccharin (C
7H
5NO
3S), 0.4 gram cumarin (C
9H
6O
2) add to dispose in 1 liter of deionized water and form.The schematic cross section of the glass substrate of Fig. 3 is integrated nickel post microarray.
2, preparation has the polymeric micro-fluidic chip substrate of microchannel, and the material of described preparation chip substrate is dimethyl silicone polymer (PDMS)
This step further comprises following substep:
1) adopt soft etching method to prepare the formpiston template of polymeric micro-fluidic chip; Formpiston template in this practical implementation is the silicon mold template, and this substep is specially: on clean monocrystalline silicon piece, coat SU-8 2050 model photoresists, the thickness of the photoresist of coating is 30～35 μ m; Cover the one side that scribbles photoresist at silicon chip to the mask that is printed on polymeric micro-fluidic chip substrate pattern then; And exposure 350 seconds under ultraviolet light, the silicon chip that finishes exposure is put in the SU-8 photoresist developing liquid and was developed 5 minutes, takes out after the back rinses well and dry up with deionized water; Obtain the silicon mold template of polymeric micro-fluidic chip, as shown in Figure 4.Polymeric micro-fluidic chip substrate pattern and electrode pattern are complementary, and the polymeric micro-fluidic chip substrate pattern in this practical implementation is a rectangle, but length and width are slightly larger than 5mm and 500 μ m respectively.
Above-mentionedly also can adopt reactive ion etching method of the prior art to prepare the formpiston template, not do at this and give unnecessary details.
2) utilize the preparation of formpiston template to have the polymeric micro-fluidic chip substrate of microchannel; This substep is specially: dimethyl silicone polymer and its curing agent are pressed (5 ~ 20): 1 mixed; After stirring, removing bubble, be poured on the silicon formpiston template; After solidifying 3 hours under 80 ℃, the dimethyl silicone polymer that solidifies is peeled off from silicon formpiston template, be polymeric micro-fluidic chip substrate with microchannel.The cross-sectional figure that has been down the formpiston template of dimethyl silicone polymer shown in Figure 5.
3, step 1 gained glass substrate and step 3 gained chip substrate are carried out bonding, promptly obtain the polymeric micro-fluidic chip of integrated nickel post microarray.
On chip substrate, punch with card punch; The hole of being beaten is the injection port 7 and outlet 8 among Fig. 1; Then with the surface 2 minute of oxygen plasma treatment chip substrate with the glass substrate that is integrated with nickel post microarray; Chip substrate and glass substrate are aimed at and bonding at microscopically, promptly obtained the polymeric micro-fluidic chip of integrated nickel post microarray.Structural representation such as Fig. 1 and shown in Figure 6 of the polymeric micro-fluidic chip of the integrated nickel post of gained microarray.
With the nanometer Fe 3 O 4 magnetic particle solution that obtains containing magnetic-particle soluble in water; The solution that will contain magnetic-particle continues to feed from the on-chip injection port 7 of polymeric micro-fluidic chip; The solution that then contains magnetic-particle is filled in around the nickel post microarray, under the effect of outside magnetic field, examines under a microscope nano magnetic particle and is adsorbed to nickel post surface; Realized the catching of magnetic-particle, as shown in Figure 8; After removing external magnetic field, be adsorbed on the liquid state that the nano magnetic particle on nickel post surface flow through and wash away, realized release magnetic-particle, as shown in Figure 9.
Claims (10)
1. the polymeric micro-fluidic chip of an integrated nickel post microarray is characterized in that, comprising:
Electrode on glass substrate, the glass-chip, the nickel post microarray on the electrode and have the chip substrate of microchannel; Described chip substrate is fixed on the glass substrate, and described electrode and described nickel post microarray are arranged in the microchannel of described chip substrate.
2. the polymeric micro-fluidic chip of integrated nickel post microarray according to claim 1 is characterized in that:
Described nickel post is cylindrical, and it highly is 10 μ m, and diameter is 30 μ m.
3. the polymeric micro-fluidic chip of integrated nickel post microarray according to claim 1 is characterized in that:
Described electrode is a cr-au electrode, and thickness is 50-100nm.
4. the preparation method of the polymeric micro-fluidic chip of each described integrated nickel post microarray among the claim 1-3 is characterized in that, comprises step:
1) on glass substrate, prepares electrode, and on electrode, prepare nickel post microarray;
2) preparation has the polymeric micro-fluidic chip substrate of microchannel, and described chip substrate adopts dimethyl silicone polymer to prepare;
3) step 1 gained glass substrate and step 3 gained chip substrate are carried out bonding, promptly obtain the polymeric micro-fluidic chip of integrated nickel post microarray.
5. the preparation method of the polymeric micro-fluidic chip of integrated nickel post microarray according to claim 4 is characterized in that:
Process at preparation electrode on the glass substrate in the step 1 is specially: adopt soft etching method that electrode pattern is transferred on the glass substrate, adopt vapour deposition method or magnetron sputtering method on the electrode pattern on the glass substrate, to prepare electrode then.
6. according to the preparation method of the polymeric micro-fluidic chip of claim 4 or 5 described integrated nickel post microarraies, it is characterized in that: described electrode is a cr-au electrode, and its thickness is 50-100nm.
7. the preparation method of the polymeric micro-fluidic chip of integrated nickel post microarray according to claim 4 is characterized in that:
Process at preparation nickel post microarray on the electrode in the step 1 is specially: adopt soft etching method with the microarray design transfer to electrode, at the microarray pattern of the electrode metal plated nickel that powers on, promptly obtain nickel post microarray then.
8. according to the preparation method of the polymeric micro-fluidic chip of claim 4 or 7 described integrated nickel post microarraies, it is characterized in that: described nickel post is cylindrical, and it highly is that 10 μ m, diameter are 30 μ m.
9. the preparation method of the polymeric micro-fluidic chip of integrated nickel post microarray according to claim 4 is characterized in that:
Step 2 is specially: adopt soft etching method or reactive ion etching legal system to be equipped with the formpiston template of polymer fluidic chip, liquid dimethyl silicone polymer is poured on the formpiston template, after the curing, through the demoulding, punching, promptly obtain having the chip substrate of microchannel.
10. the preparation method of the polymeric micro-fluidic chip of integrated nickel post microarray according to claim 9 is characterized in that:
Described formpiston template is the silicon mold template.
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| CN103908306A (en) * | 2014-04-17 | 2014-07-09 | 山东师范大学 | Circulating tumor cell in-vivo capturing device and circulating tumor cell in-vivo capturing method on basis of indwelling needles |
| CN105268491A (en) * | 2015-10-26 | 2016-01-27 | 中国工程物理研究院激光聚变研究中心 | Method for preparing micro-fluidic/milli-fluidic chip by using detachable template |
| CN106480039A (en) * | 2016-10-13 | 2017-03-08 | 南京大学 | A kind of method that utilization micro-fluidic chip screens aptamers |
| CN112121874A (en) * | 2020-09-27 | 2020-12-25 | 南京南智先进光电集成技术研究院有限公司 | Preparation method of micro-channel structure chip and micro-channel structure chip |
| CN112725417A (en) * | 2020-12-14 | 2021-04-30 | 苏州拉索生物芯片科技有限公司 | Chip electroplating device for improving micro-bead hole-entering rate and electroplating method thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103908306A (en) * | 2014-04-17 | 2014-07-09 | 山东师范大学 | Circulating tumor cell in-vivo capturing device and circulating tumor cell in-vivo capturing method on basis of indwelling needles |
| CN105268491A (en) * | 2015-10-26 | 2016-01-27 | 中国工程物理研究院激光聚变研究中心 | Method for preparing micro-fluidic/milli-fluidic chip by using detachable template |
| CN106480039A (en) * | 2016-10-13 | 2017-03-08 | 南京大学 | A kind of method that utilization micro-fluidic chip screens aptamers |
| CN106480039B (en) * | 2016-10-13 | 2019-11-12 | 南京大学 | A method of aptamers are screened using micro-fluidic chip |
| CN112121874A (en) * | 2020-09-27 | 2020-12-25 | 南京南智先进光电集成技术研究院有限公司 | Preparation method of micro-channel structure chip and micro-channel structure chip |
| CN112121874B (en) * | 2020-09-27 | 2021-12-10 | 南京南智先进光电集成技术研究院有限公司 | Preparation method of micro-channel structure chip and micro-channel structure chip |
| CN112725417A (en) * | 2020-12-14 | 2021-04-30 | 苏州拉索生物芯片科技有限公司 | Chip electroplating device for improving micro-bead hole-entering rate and electroplating method thereof |
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Application publication date: 20120919 |