CN1563998A - Microcurrent controlled chip detection combiner having general and integral and high efficiency radiation - Google Patents
Microcurrent controlled chip detection combiner having general and integral and high efficiency radiation Download PDFInfo
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- CN1563998A CN1563998A CN 200410014666 CN200410014666A CN1563998A CN 1563998 A CN1563998 A CN 1563998A CN 200410014666 CN200410014666 CN 200410014666 CN 200410014666 A CN200410014666 A CN 200410014666A CN 1563998 A CN1563998 A CN 1563998A
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- 238000001514 detection method Methods 0.000 title description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 22
- 210000001736 Capillaries Anatomy 0.000 claims abstract description 14
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 11
- 239000003365 glass fiber Substances 0.000 claims abstract description 9
- 230000005284 excitation Effects 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims description 21
- 238000001816 cooling Methods 0.000 claims description 15
- 239000000463 material Substances 0.000 claims description 11
- 230000003287 optical Effects 0.000 claims description 8
- 229910052782 aluminium Inorganic materials 0.000 claims description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminum Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 4
- 229920002521 Macromolecule Polymers 0.000 claims description 3
- 239000004411 aluminium Substances 0.000 claims description 2
- 239000011521 glass Substances 0.000 claims description 2
- 230000001105 regulatory Effects 0.000 claims description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 1
- 229910052802 copper Inorganic materials 0.000 claims 1
- 239000010949 copper Substances 0.000 claims 1
- 239000007769 metal material Substances 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 22
- 238000001962 electrophoresis Methods 0.000 abstract description 15
- 238000001499 laser induced fluorescence spectroscopy Methods 0.000 abstract description 8
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 abstract description 3
- 238000003379 elimination reaction Methods 0.000 abstract 2
- 238000004458 analytical method Methods 0.000 description 13
- 230000000694 effects Effects 0.000 description 11
- 239000007853 buffer solution Substances 0.000 description 10
- 238000005251 capillar electrophoresis Methods 0.000 description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 239000000835 fiber Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- CXQXSVUQTKDNFP-UHFFFAOYSA-N Simethicone Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 2
- 238000007334 copolymerization reaction Methods 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000004328 sodium tetraborate Substances 0.000 description 2
- 235000010339 sodium tetraborate Nutrition 0.000 description 2
- 210000003666 Nerve Fibers, Myelinated Anatomy 0.000 description 1
- 206010036618 Premenstrual syndrome Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000000240 adjuvant Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000011031 large scale production Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001012 micellar electrokinetic chromatography Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004801 process automation Methods 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
Abstract
The integrated unit includes microflow controlled chip, laser, photomultiplier, micro object lens, filter, high voltage power supply dedicated to capillary of chip and platinum electrode. Separation electrode and electrode of adding sample are integrated on platform of radiator. Ends of platinum electrode are exposed on surface of the platform. Laser through incident optical fiber is fixed on 3D adjuster for positioning excitation path and path of receiving fluorescence. Radiator carries out high performance heat elimination for chip electrophoresis. Laser induced fluorescence testing is carried out for object in non-cofocused mode. The unit improves heat elimination and tests fluorescein of sample.
Description
Technical field
The present invention is that a kind of chip capillary cataphoresis light of integrated heat spreader detects integrated apparatus, specifically, be that the integrated laser induced fluorescence detects and capillary electrophoresis chip on heat abstractor, position by accurate control laser incidence point, the advantage of performance heating radiator high efficiency and heat radiation is carried out high efficiency separation and high-sensitivity detection to sample.
Background technology
Micro-total analysis system is one of research forward position focus of present analysis science.Traditional analytical instrument and means all need lot of manpower and material resources, and whole process automation degree is lower, and simultaneously the consumption of the reagent and the energy is very big, and these have caused adverse effect in from now on development all for analysis science.Under this background, the research of micro-total analysis system is arisen at the historic moment.Micro-total analysis system can be with the whole analysis process in laboratory such as sample preparation, sample filtering, sample separation so that sample detection etc. are integrated in carries out on the little chip block, can realize the robotization and the microminiaturization of whole analysis process, enter into huge numbers of families and lay the foundation for analytical instrument from now on becomes consumer product.
Focus is more in the research of present micro-total analysis system, and one of them important focus is exactly the microfluidic analysis system that is integrated in chip.The commercial detecting instrument of success adopts glass-chip and confocal laser induced fluorescence (LIF) detecting device more at present, and it can detect the material that Stimulated Light induces fluorescence signal at post, and sensitivity and separation efficiency are higher.But the manufacturing of glass-chip is comparatively complicated, and cost is also higher, is difficult to large-scale popularization.Focus type LIF detecting device is owing to will use the confocal fluorescent microscope as optical system altogether, and complex structure is difficult to realize microminiaturization, runs counter to the original intention of " micro-total analysis system ".
Macromolecular material is used for the manufacturing of micro-fluidic chip at present, and its method for making is simple, and is with low cost, is fit to large-scale production and promotes.But because the too late glass of the heat dispersion of most of macromolecular material, the Joule heat that this has increased in the post has reduced the post that separates and has imitated.On photodetector, the burnt light path of non-copolymerization is comparatively simple, can realize that microminiaturization is integrated, but than being total to focus type LIF detecting device, its detection efficiency is lower, and detectability is not high.Another critical problem is that incident laser accurate location on pipeline is difficult simultaneously, because the microminiaturization of pipeline, this has become an outstanding problem.
In electrophoretic separation, realize that fast the separation field intensity that applies of separation requirement is high as far as possible efficiently, yet high field intensity can produce too much Joule heat and separation efficiency is had a negative impact.In chip capillary cataphoresis, though radiating efficiency will be higher than conventional Capillary Electrophoresis, but high field intensity is separated the restriction that still is subjected to Joule heat, micellar electrokinetic chromatography method (MECC) for example, reduce the influence that post is imitated because be subjected to Joule heat, be difficult to widespread use in chip, joule heating effect has also restricted the use of high concentration buffer solution simultaneously.Therefore how to improve the radiating efficiency of chip electrophoresis, just become to improve the key problem in technology that degree of separation was imitated and improved to post, thereby also just become a focus of micro-fluidic research.
Therefore, development integrated-type incorporate low cost, high-level efficiency, universal chip capillary cataphoresis device have become micro-total analysis system commercialization early and have moved towards the only way which must be passed of huge numbers of families.
Summary of the invention
The present invention uses simple instrument and equipment, has overcome some shortcomings of prior art.By integrated laser induced fluorescence pick-up unit and capillary electrophoresis chip on heating radiator, obviously improved joule heating effect in the post; Realized the focusing location of light path simultaneously easily by the miniature three-dimensional regulator, device can be used for the detection of actual sample.The method of a kind of convenience and effective placement and fixed electorde also is provided here, and the commercialization that is very beneficial for micro-total analysis system is used.
The technical solution adopted for the present invention to solve the technical problems is:
The micro-fluidic chip of universal integrated efficient heat radiation detects integrated apparatus, comprise micro-fluidic chip, laser instrument, optical fiber, photomultiplier, microcobjective, optical filter, chip capillary high-voltage power supply special, platinum electrode are formed, other is provided with the radiator core fin supporting platform of integrated micro three-dimensional regulation device, and integrated separate mesh electrode and application of sample electrode expose the platinum electrode end at platform surface on cooling platform.
Heating radiator by an aluminum thermal fin and under radiator fan constitute.Integrated separate mesh electrode and application of sample electrode expose the platinum electrode end at platform surface on cooling platform.Is film about 0.3-1mm with macromolecular material being paved into thickness on the cooling platform, solidifies the egative film part of back as chip, then the pipeline chip is fitted on the film, forms complete micro-fluidic chip.At heating radiator platform one side fixed support, upper fixed three-dimensional regulation device, regulator is clamped laser fiber.The angle of light incident and platform surface level keep 45 degree, accept fluorescence signal with optical fiber.Utilize the three-dimensional regulation device to position to laser excitation light path and fluorescence receiving light path.
Wherein platinum electrode is used as separation high pressure, application of sample high pressure, separation ground connection and the application of sample ground-electrode of microchannel.After the fluorescence signal that detects is spread out of by optical fiber,, collect, export by computing machine at last by data collector through amplifying the optical filtering light path.
The optimal operating parameter of this technology is: separation voltage: 200V/cm~1400V/cm; Running buffer PBS (phosphate) solution, SDS buffer solution.
Concrete effect of the present invention is as follows: the present invention adopts macromolecular material to make micro-fluidic chip, its method for making is simple, with low cost, use the cooling system of this device to improve the negative effect of the joule heating effect of chip capillary cataphoresis under high field intensity, in electrophoretic separation, realize fast, efficient, guaranteed Gao Zhuxiao and better separating effect.In the PBS of high concentration buffer solution and SDS buffer solution, can under very high field intensity, guarantee stable separation electric current, and effectively reduce joule heating effect.Simultaneously this device has thoroughly solved the problem that light path and pipeline are difficult to aim in non-copolymerization Jiao optical detection technique, has guaranteed the reappearance that testing result is good.This device utilizes the heating radiator platform to separate, detects two parts and become one in addition, and the electrode stationarity is good, and microminiaturized degree height has reduced cost and consumption.On photodetector, incident laser is located more accurate on microminiaturized pipeline.
Description of drawings
Fig. 1 detects the side-looking organigram of integrated apparatus for the chip capillary cataphoresis light of integrated heat spreader of the present invention.Among the figure: 1, heat radiator; 2, fan; 3, micro-fluidic chip; 4, PDMS (to dimethione) film backsheet; 5, electrode; 6, the three-dimensional regulation device; 7, laser instrument; 8, optical fiber; 9, microcobjective and optical filter; 10, the Capillary Electrophoresis high-voltage power supply; 11, photomultiplier; 12, high-voltage power supply and data sink; 13, the Computer Processing terminal; 14, silica fibre.
Fig. 2 is the vertical view of chip capillary cataphoresis integrated electrochemical of the present invention system.3, micro-fluidic chip, 4, the PDMS film backsheet, 15, check point, 16, platinum electrode passes the position.
When Fig. 3 detects for utilizing the present invention, in the 100mmol/L PBS buffer solution, there is and do not have ohm curve comparison diagram of cooling system.
When Fig. 4 detects for utilizing the present invention, pipeline under different field intensity, in the certain hour section, have with do not have cooling system under separate electric current variation tendency comparison diagram.
When Fig. 5 detects for utilizing the present invention, in the 50mmol/L SDS+10mmol/L borax buffer solution, there is and do not have ohm curve comparison diagram of cooling system.
When Fig. 6 detects for utilizing the present invention, 1 * 10
-6The electrophoretogram that the mol/L fluorescein detects.
Embodiment:
The invention will be further described below in conjunction with drawings and Examples.
Chip capillary cataphoresis light at integrated heat spreader shown in Figure 1 detects in the integrated apparatus, main heating radiator by an integrated micro three-dimensional regulation device, the chip supporting platform, comprise micro-fluidic chip, an Aluminium Radiator simultaneously, a radiator fan, a laser emitter, some optical fiber, a photomultiplier, a back of the body formula projection cathode-ray tube PMT, a microcobjective, a tablet filter, a condenser lens, a chip capillary high-voltage power supply special, some platinum electrodes, a composition such as microscope.Heating radiator by an aluminum thermal fin and under radiator fan constitute.Integrated separate mesh electrode and application of sample electrode expose the platinum electrode end at platform surface on cooling platform.Is film about 0.5mm with macromolecular material being paved into thickness on the cooling platform, solidifies the egative film part of back as chip, then the pipeline chip is fitted on the film, forms complete micro-fluidic chip.At heating radiator platform one side fixed support, upper fixed three-dimensional regulation device, regulator is clamped laser fiber.The angle of light incident and platform surface level keep 45 degree, accept fluorescence signal with optical fiber.Utilize the three-dimensional regulation device to position to laser excitation light path and fluorescence receiving light path.Thereby the integrated laser induced fluorescence detects and capillary electrophoresis chip on heat abstractor, and by the position of accurate control laser incidence point, the advantage of performance heating radiator high efficiency and heat radiation is carried out high efficiency separation and high-sensitivity detection to sample.
To receive optical fiber, and separate high-field electrode, separate ground-electrode, application of sample high-field electrode, the application of sample ground-electrode is integrated is solidificated in the heating radiator, earlier macromolecule (4) is spread out in spreader surface before the experiment, makes thin layer.Then chip (3) is fitted tightly on thin layer, place the liquid pool on the chip to hit exactly at electrode (5).Laser beam incident fibre (14) is fixed on (6) on the three-dimensional regulation device, by regulating the location that the three-dimensional regulation device carries out excitation light path and fluorescence receiving light path.Make the application of sample of chip and separating pipe all be full of damping fluid with vacuum pump; Each electrode is connected chip used Capillary Electrophoresis with on the high-voltage power supply (10).The fluorescence signal that detection obtains enters photomultiplier (11) and is converted into electric signal through microcobjective and optical filter (9).Photomultiplier links to each other with data sink (12) with high-voltage power supply.High-voltage power supply all links to each other with computing machine (7) with high-voltage power supply with data sink and chip capillary cataphoresis.When detecting, open radiator fan (2), the speed-up chip heat radiation.
In order to measure the joule heating effect of pipeline, determine optimum separation voltage simultaneously, generally can make Ohm law curve (I-V curve) by experiment, according to Ohm law
V=IR
When system load (capillary resistance R) was constant, linear by electric current capillaceous (I) and impressed voltage (V), along with V raises, the Joule heat of generation increased.If chip can not in time distribute the Joule heat of generation, the resistance of buffer solution then reduces, and load diminishes, and electric current increases departs from linear.Therefore, under selected condition, make ohm curve, just can determine optimum separation voltage by flex point.
Fig. 4 is in the 100mMPBS buffer solution, has and do not have ohm curve comparison diagram of cooling system.We have removed heat radiator and fan from device, the PBS solution of high concentration is made ohm curve, show among the figure that curve began departs from linear when field intensity reached 200V/cm.And after adding heat abstractor, flex point appears near the 400/cm, and this has shown that device has very significantly improvement to heat radiation, has promoted nearly one times with optimum separation voltage.
Fig. 5 adopts 100mmol/L PBS as buffer solution equally, and under different field intensity, making alive continues 25-30s, and separation electric current variation tendency compares under the cooling system to having or not.We can see from figure, and along with the increase of field intensity, on the common unit that does not have heat radiation, electric current rises very fast, and particularly when 550V/cm, electric current almost linearly rises.And after integrated heat radiating device, under high field intensity, electric current is quite steady, can keep more stable separation electric current when 550V/cm.This imitates for improving post, and the negative effect that reduces Joule heat has fairly obvious effect.
Fig. 6 is in the 50mmol/L SDS+10mmol/L borax buffer solution, has and do not have ohm curve comparison diagram of cooling system.Because the adding of high concentration SDS adjuvant, make that joule heating effect significantly increases in the pipeline, this has brought difficulty for the application of MECC under high field intensity.Do not having under the situation of cooling measure, ohm point of inflexion on a curve appears at 800V/cm, and integrated after the heating radiator, flex point appears near the 1300V/cm, and this has greatly promoted the optimal separation electric current of MECC.
Fig. 7 is for utilizing this integrated device, to 1 * 10
-6The mol/L fluorescein carries out the electrophoretogram of actual detected.Its result has proved that this device can effectively detect separation to actual sample, and can reach comparatively desirable detectability.
In view of the microfluidic analysis system at analytical chemistry, special in the research of Analytical Chemistry in Life Science and the importance of application, so the chip capillary cataphoresis light of this integrated heat spreader detects the invention of integrated apparatus, will have broad application prospects, and produce huge social and economic benefit.
Claims (6)
1, the micro-fluidic chip of universal integrated efficient heat radiation detects integrated apparatus, comprise micro-fluidic chip, laser instrument, optical fiber, photomultiplier, microcobjective, optical filter, chip capillary high-voltage power supply special, platinum electrode are formed, it is characterized in that being provided with the radiator core fin supporting platform, integrated separate mesh electrode and application of sample electrode on cooling platform, expose the platinum electrode end at platform surface, laser instrument is fixed on (6) on the three-dimensional regulation device by incident optical (14), by regulating the location that the three-dimensional regulation device carries out excitation light path and fluorescence receiving light path.
2, the micro-fluidic chip by the described universal integrated efficient heat radiation of claim 1 detects integrated apparatus, the structure that it is characterized in that micro-fluidic chip is to be provided with macromolecule material film on cooling platform, macromolecule material film solidifies the egative film part of back as chip, then the pipeline chip is fitted on the film, forms complete micro-fluidic chip.
3, the micro-fluidic chip by the described universal integrated efficient heat radiation of claim 1 detects integrated apparatus, it is characterized in that macromolecular material is paved into the film that thickness is 0.3-1mm
4, the micro-fluidic chip by the described universal integrated efficient heat radiation of claim 1 detects integrated apparatus, it is characterized in that the chip egative film is directly linked to each other with heating radiator, the chip egative film can be glass or macromolecular material, and heating radiator adopts aluminium or copper metal material by a heat radiator or at heat radiator.
5, the micro-fluidic chip by the described universal integrated efficient heat radiation of claim 1 detects integrated apparatus, it is characterized in that heat radiator bottom choosing dress fan constitutes.
6, the micro-fluidic chip by the described universal integrated efficient heat radiation of claim 1 detects integrated apparatus, it is characterized in that application of sample and separate mesh electrode are fixed in the heating radiator, and the fluorescence receiving light path is integrated in the heating radiator.
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100367033C (en) * | 2005-04-21 | 2008-02-06 | 南京大学 | Microflow control chip integrated unit in integrated constant temperature system in high efficiency |
CN100414288C (en) * | 2005-07-27 | 2008-08-27 | 北京工业大学 | Miniature millimeter laser induced fluorescent detector for biological chip |
CN103901009A (en) * | 2014-04-22 | 2014-07-02 | 许昌学院 | Optical fiber scanning type laser-induced fluorescence detection system |
RU2570706C1 (en) * | 2014-07-22 | 2015-12-10 | Федеральное государственное унитарное предприятие "Государственный научный центр "Научно-исследовательский институт органических полупродуктов и красителей" (ФГУП "ГНЦ "НИОПИК") | Method for qantitative determination of sodium fluorescein in substance and thereof-based medication |
CN106770078A (en) * | 2016-11-14 | 2017-05-31 | 无锡艾科瑞思产品设计与研究有限公司 | A kind of LIF food detector |
CN109917274A (en) * | 2019-03-27 | 2019-06-21 | 深圳市安思科电子科技有限公司 | A kind of stable type detection device with regulatory function for chip |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN2501046Y (en) * | 2001-10-31 | 2002-07-17 | 东北大学 | Miniflow controlled chip analysis semiconductor laser induced fluorescence detector |
US20030232450A1 (en) * | 2002-06-13 | 2003-12-18 | Yoshikazu Yoshida | Microfluidic device and method for producing the same |
CN1206527C (en) * | 2002-07-31 | 2005-06-15 | 中国科学院生态环境研究中心 | Tunnel capillary electrophoretic chemiluminescence testing microfluid control chip |
CN2572407Y (en) * | 2002-10-08 | 2003-09-10 | 中国科学院大连化学物理研究所 | Multi-channel chip ampere detector and detection system |
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2004
- 2004-04-16 CN CNB2004100146669A patent/CN100380126C/en not_active Expired - Fee Related
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100367033C (en) * | 2005-04-21 | 2008-02-06 | 南京大学 | Microflow control chip integrated unit in integrated constant temperature system in high efficiency |
CN100414288C (en) * | 2005-07-27 | 2008-08-27 | 北京工业大学 | Miniature millimeter laser induced fluorescent detector for biological chip |
CN103901009A (en) * | 2014-04-22 | 2014-07-02 | 许昌学院 | Optical fiber scanning type laser-induced fluorescence detection system |
CN103901009B (en) * | 2014-04-22 | 2016-11-23 | 许昌学院 | A kind of laser-induced fluorescence detection system of optical fiber scan type |
RU2570706C1 (en) * | 2014-07-22 | 2015-12-10 | Федеральное государственное унитарное предприятие "Государственный научный центр "Научно-исследовательский институт органических полупродуктов и красителей" (ФГУП "ГНЦ "НИОПИК") | Method for qantitative determination of sodium fluorescein in substance and thereof-based medication |
CN106770078A (en) * | 2016-11-14 | 2017-05-31 | 无锡艾科瑞思产品设计与研究有限公司 | A kind of LIF food detector |
CN109917274A (en) * | 2019-03-27 | 2019-06-21 | 深圳市安思科电子科技有限公司 | A kind of stable type detection device with regulatory function for chip |
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