CN100561226C - Low-voltage driving array electrode type capillary electrophoresis chip - Google Patents
Low-voltage driving array electrode type capillary electrophoresis chip Download PDFInfo
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- CN100561226C CN100561226C CNB2006102001837A CN200610200183A CN100561226C CN 100561226 C CN100561226 C CN 100561226C CN B2006102001837 A CNB2006102001837 A CN B2006102001837A CN 200610200183 A CN200610200183 A CN 200610200183A CN 100561226 C CN100561226 C CN 100561226C
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- raceway groove
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Abstract
The invention belongs to the micro-total analysis system studying technological domain in the analytical chemistry, in order in the chip capillary cataphoresis detachment process, to realize the low voltage drive sample feeding.The principle that it is characterized in that utilizing electroosmotic flow in the Capillary Electrophoresis to drive, the little raceway groove of etching Capillary Electrophoresis on cover glass, and, produce array electrode type capillary electrophoresis chip with the method sealing-in substrate and the cover plate of thermal bonding.The sample introduction raceway groove of " ten " font capillary electrophoresis chip with separate raceway groove on be provided with a series of electrodes respectively, promptly at buffer pool between the cross raceway groove, and the sample waste liquid pool is between the cross raceway groove, all be provided with array electrode respectively, by designing the combination of different voltage, apply sample introduction that voltage realizes sample and separate in the electrode cocycle.Effect of the present invention and benefit are to reduce the sample introduction and the separation voltage of Capillary Electrophoresis by a relatively large margin, and it is real integrated and microminiaturized that micro-total analysis system is realized.
Description
Technical field
The invention belongs to the micro-total analysis system studying technological domain in the analytical chemistry, expectation can utilize lower separation voltage to replace present high separation voltage, the microminiaturization of realization capillary electrophoresis chip and integrated.
Background technology
Capillary electrophoresis chip is an important branch in the micro-total analysis system research field, it is the microanalysis device that just occurs the nearly more than ten years, it is on the basis of conventional Capillary Electrophoresis principle and technology, utilize micro-processing technology on matrixes such as silicon, glass, plastics, to etch flat pipeline and other functional unit, by different piping networks, the design of functional unit, realize sample introduction, reaction, separation and the detection of sample, be a kind of multifunction fast, the microscale chemical experiment apparatus of efficient, low consumption.At present, the aspects such as compartment analysis, immunoassay, medical diagnosis on disease and Pharmaceutical Analysis that are applied to DNA analysis and order-checking, protein and polypeptide analysis, biological cell of capillary electrophoresis chip success.
Most typical " ten " font capillary electrophoresis chip as shown in Figure 1.Vertical raceway groove is the sample raceway groove among the figure, and horizontal raceway groove is for separating raceway groove, the sample raceway groove with separate raceway groove and be crossed as " ten " font.There are four liquid storage tanks on the top of raceway groove, is respectively sample cell, buffer pool, sample waste liquid pool and waste liquid pool.Capillary electrophoresis chip earlier applies voltage at sample raceway groove (among Fig. 1 between 2 and 3) when carrying out electrophoretic analysis, sample flows to 3 from 2 through cross junction under the effect of electroosmotic flow; Then voltage is switched to and separate raceway groove (among Fig. 1 between 1 and 4), make the one section sample solution that is stored in the cross junction place under the promotion of electroosmotic flow, enter the separation raceway groove and separates.Because the high separation voltage that is applied is separating raceway groove generation gradient electric field, and each component produces the differences of mobility in the sample because of the different meetings of specific charge in damping fluid, so each component will be moved with friction speed under the effect of electric field force in the sample, thereby make different component district bands be positioned at the check point D that split tunnel is not held in different moment processes.At this moment, utilize certain detection method just can obtain the electrophoretic separation spectrogram, finish the compartment analysis process of sample.
In the analytic process of capillary electrophoresis chip, need apply high-voltage power supply make separate produce on the raceway groove enough field intensity (300～800V/cm), general separation voltage from several hectovolts to several kilovolts.Therefore, have only tens to twenties square centimeters micro-fluidic chip to compare with area, analytical equipment is bulky, is difficult to realize real integrated and microminiaturized.Therefore, people utilize lower separation voltage to realize the separation of sample exploring.
People (Yu-Cheng Lin such as the calendar year 2001 Taiwan success Yu Cheng-Lin of university, Wei-Da Wu.Sensors andActuators B.2001,73:54-62.), at first the DC low-voltage isolation technics is applied in the capillary electrophoresis chip, they have proposed the design philosophy of the low separation voltage driving of array electrode type capillary electrophoresis chip.Array electrode (as shown in Figure 2) promptly is set on the separation raceway groove of " ten " font capillary electrophoresis chip, by applying voltage in the electrode cocycle, make the detachment process of sample in the kapillary raceway groove similar substantially to traditional capillary electrophoresis separation conditions needed, they estimate separation voltage can be dropped to original 1/5th on the basis that theory is calculated.2002, people (Wu Ying such as the Wu Ying of University Of Chongqing, Wen Zhiyu, Zhang Zhengyuan etc. optical precision engineering .2003,11 (2): 130-135) with the method for diffusing, doping at a series of equally spaced electrode pair of having made on the silicon chip on the capillary electrophoresis separation passage (its structure is identical with Fig. 2), on cover glass, made " ten " font capillary channel, by designing position and the time that separation voltage applies on the corresponding circuit control split tunnel.In order to guarantee material detachment process fast, they have proposed the motion gradient fields model that low-voltage is separated, the position that applies of low-voltage is changed along with the motion of material, on split tunnel, form the variation field intensity of motion, make compounding substances under the field intensity effect of this motion change, finish detachment process.2004, the old superfine people of IEAS has also delivered the article (Chen Chao of relevant lineation electrode electrophoresis chip, Zhao Zhan, open the army of fighting. micro-nano electronic technology .2003,7/8:362-368), the thought that people such as its design philosophy and Taiwan Yu Cheng-Lin propose is identical, is matrix material with common microslide and organic polymer PDMS, and finished the hardware system design, it is reported that its maximum operating voltage reduces to 400 volts.
At present, actually rare both at home and abroad to the report of the capillary electrophoresis chip that replaces high separation voltage with low-voltage, also do not realize commercialization.But forefathers' work proof might be broken away from the plus high-pressure power supply as long as constantly improve chip structure design and manufacture craft, make capillary electrophoresis chip really become microminiaturized and integrated compartment analysis system.Therefore, the development of low-voltage driving array electrode type electrophoresis chip is very significant, and wide application prospect is arranged.
Summary of the invention
The purpose of this invention is to provide a kind of the sample introduction raceway groove with separate the capillary electrophoresis chip that raceway groove all is provided with array electrode, reduce separation voltage and sample introduction voltage, with the microminiaturization that realizes micro-total analysis system equipment and integrated.
Technical scheme of the present invention is:
Sputter platinum film on cover glass is etched into a series of electrodes with the photoetching corroding method with it.Wherein: " ten " word crossing is that be parallel to each other and a series of array electrodes vertical with separating raceway groove between the waste liquid pool; " ten " word crossing is two and is parallel to each other and the electrode vertical with the sample introduction raceway groove between the sample waste liquid pool; " ten " word crossing also is two and is parallel to each other and the electrode vertical with separating raceway groove between the buffer pool.Concrete structure as shown in Figure 3.
The little raceway groove of etching on glass substrate " ten " font is produced 4 liquid storage tanks with the method for ultrasonic punching, as shown in Figure 4; Then glass substrate and cover glass are sealed it with the method for thermal bonding; Utilize platinum filament that the electrode in the chip is drawn out on the circuit board with the method for pressure welding at last, electrode is carried out switching controls by control circuit.
Owing to also made array electrode at the sample introduction raceway groove, by control circuit electrode is switched, just can under lower sample introduction voltage conditions, obtain the raceway groove built-in potential distribution results identical, as shown in Figure 5 with the high pressure sample introduction.In addition, between the buffer pool of " ten " font capillary electrophoresis separation raceway groove and crossing, also be provided with array electrode, the sample that not only can reduce " ten " word crossing pushes the required initially-separate voltage that applies when separating raceway groove, folder stream voltage in the time of can also reducing extraining sampling has the effect that kills two birds with one stone.
Effect of the present invention with benefit is: by the sample introduction raceway groove with separate raceway groove array electrode be set respectively, the sample introduction voltage and the separation voltage that are applied on the capillary electrophoresis chip have been reduced, for the analysis of finishing Capillary Electrophoresis under low voltage provides valid approach, this invention will help to realize the microminiaturization of micro-total analysis system equipment and integrated.
Description of drawings
Fig. 1 is the capillary electrophoresis chip structural representation.
Among the figure: 1 buffer pool, 2 sample cells, 3 sample waste liquid pools, 4 waste liquid pools, 5 detecting devices, 6 high-voltage power supplies, 7 sample introduction raceway grooves, 8 separate raceway groove.
Fig. 2 is a split tunnel array electrode structural representation.
Among the figure: 10 capillary electrophoresis chips, 9 separate the array electrode on the raceway groove, 5 detecting devices.
Fig. 3 is a cover plate array electrode structural representation of the present invention.
Among the figure: 11 waste liquid pool contact conductors, 12 sample cell contact conductors, 13 buffer pool contact conductors, 14 sample waste liquid pool contact conductors, 15 separate the array electrode of raceway groove, the array electrode of 16 sample introduction raceway grooves, 17 bond pad.
Fig. 4 is a substrate Capillary Electrophoresis Micro Channel Architecture synoptic diagram of the present invention.
Among the figure: 1 buffer pool, 2 sample cells, 3 sample waste liquid pools, 4 waste liquid pools, 8 separate raceway groove, 7 sample introduction raceway grooves.
Fig. 5 is the raceway groove built-in potential distribution comparison diagram of low-voltage sample introduction of the present invention and conventional sample introduction.
Among the figure: (a) crossing's Potential Distributing in raceway groove during conventional sample introduction,
(b) crossing's Potential Distributing in the raceway groove during low-voltage sample introduction.
Fig. 6 is the chip of the present invention required initially-separate voltage that applies and regular situation lower channel built-in potential distribution comparison diagram when sample enters the separation raceway groove.
Among the figure: (c) crossing's Potential Distributing in raceway groove during conventional initially-separate,
Crossing's Potential Distributing in raceway groove when (d) low-voltage is separated.
Fig. 7 is chip of the present invention raceway groove built-in potential distribution comparison diagram when extraining sampling and conventional extraining sampling.
Among the figure: (e) crossing's Potential Distributing in raceway groove during conventional extraining sampling,
(f) crossing's Potential Distributing in the raceway groove during low-voltage extraining sampling.
Embodiment
Be described in detail the specific embodiment of the present invention below in conjunction with technical scheme and accompanying drawing.
At present, the input mode of capillary electrophoresis chip mainly is an electrokinetic injection, promptly under the effect of extra electric field, relies on electroosmotic flow that sample is sent into the separation raceway groove.Under the electric field force effect, the characteristics of motion of charged species undergoes is extremely complicated in little raceway groove, and is all multifactor relevant with the viscosity of the specific charge of the pH value of the shape of the size that applies voltage in the raceway groove, raceway groove, damping fluid, particulate, solution, environment temperature etc.To apply voltage to sample introduction and the influence that separates in order analyzing, but only to change the variation that voltage produced that applies under all identical condition of apparent other factors.
The variation of impressed voltage produces the variation that potential gradient distributes in little raceway groove, it is the direct driving force that drives the sample particle movement.Therefore, understand the variation that potential gradient that different impressed voltages produces distributes in little ditch, just can the moving situation of interpret sample in little raceway groove.So, will utilize method of finite difference to carry out little raceway groove built-in potential gradient The results of numerical simulation below, the specific embodiment of the present invention is described.
During routine Capillary Electrophoresis sample introduction, at first between 2 and 3 two ends as shown in Figure 1, apply sample introduction voltage, between 1 and 4 two ends, apply folder stream voltage, to guarantee that sample is in being flowed to sample waste liquid pool process by sample cell, sample in crossing to separating the raceway groove expansion, this moment in the Potential Distributing of little raceway groove crossing shown in Fig. 5 (a).Curve among the figure is the equipotential line, works as V
1: V
2: V
3: V
4=0.8: 1: 0: 0.8 o'clock, the electric potential difference of adjacent two equipotential lines was 0.01.At this moment, sample will reduce direction along electromotive force and move, and promptly flow to sample waste liquid pool 3 by sample cell 2.Because the crossing's channel direction of both sides separation to the left and right electromotive force raises gradually, the sample of crossing is subjected to separating the extruding of raceway groove, can not spread to both sides, thereby guarantee that sample flows to end points 1 by end points 2 in the sample introduction process.When adopting the capillary electrophoresis chip of the present invention's design,, adopt same sampling condition: V owing to increased array electrode at the sample introduction raceway groove
1: V
2: V
3: V
4=0.8: 1: 0: 0.8 o'clock, the distribution of crossing's equipotential line was shown in Fig. 5 (b), and the equipotential line density increases, and potential gradient increases, and helped sample moving in the sample introduction raceway groove.According to Theoretical Calculation, if Fig. 5 (b) is obtained and the identical Potential Distributing of Fig. 5 (a), the 40%-30% that only is Fig. 5 (a) at port 2 and 3 voltages that apply of port of Fig. 5 (b) then.In experiment, when adopting the capillary electrophoresis chip sample introduction of the present invention's design, sample introduction voltage is reduced to 250V by the 700V of conventional method.This result shows, the capillary electrophoresis chip of the present invention's design, owing to array electrode is set at the sample introduction raceway groove, thus greatly reduce sample introduction voltage.
After finishing sample feeding,, just can carry out the separation of sample as long as change the voltage ratio of 4 ports.With in the chip of the present invention and conventional capillary electrophoresis chip shown in Figure 6, the raceway groove built-in potential distributes and relatively is to adopt example and top described identical mode after applying initially-separate voltage, and the situation that separation voltage reduces is described below.Fig. 6 (c) has provided in conventional capillary electrophoresis chip, and the separation voltage ratio that applies at 4 ports is V
1: V
2: V
3: V
4=1: 0.3: 0.3: 0 o'clock, the Potential Distributing situation of crossing.Fig. 6 (d) has provided in the capillary electrophoresis chip of the present invention design, the Potential Distributing situation of crossing when applying the separation voltage of same proportionate relationship.By finding out among the figure, under same voltage combination condition, the equipotential line density increases, and potential gradient increases, and helps sample moving in separating raceway groove.The Theoretical Calculation separation voltage can be reduced to about the 40%-30% of conventional value.
Accompanying drawing 7 has provided the extraining sampling and conventional folder of the array electrode type capillary electrophoresis chip of the present invention's design
Flow to the raceway groove built-in potential distribution comparison diagram of sample.By in the accompanying drawing 7 as can be seen, under identical voltage combined situation: V
1: V
2: V
3: V
4=0.8: 1: 0: 0.8, the potential gradient in " ten " word raceway groove was bigger, more helped sample moving in the sample introduction raceway groove, also sample was produced more effective extruding simultaneously, had prevented the diffusion of sample.
In sum, just because of the present invention the sample introduction raceway groove with separate raceway groove and designed the array electrode raceway groove simultaneously, thereby reduced extraining sampling voltage and separation voltage.
Claims (1)
1, low-voltage driving array electrode type capillary electrophoresis chip, be to utilize the principle that electroosmotic flow drives in the Capillary Electrophoresis, the sample introduction raceway groove of " ten " font capillary electrophoresis chip with separate raceway groove on be provided with a series of electrodes respectively, by applying voltage in the electrode cocycle, the sample introduction of realizing sample with separate; It is characterized in that: between the waste liquid pool, be provided with a series of being parallel to each other and the array electrode vertical with separating raceway groove in " ten " word crossing; , be provided with two and be parallel to each other and the electrode vertical between the sample waste liquid pool in " ten " word crossing with the sample introduction raceway groove; , be provided with two and be parallel to each other and the electrode vertical between the buffer pool in " ten " word crossing with separating raceway groove; By the voltage composite design, reach the voltage that applies when reducing sample introduction and separating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006102001837A CN100561226C (en) | 2006-02-28 | 2006-02-28 | Low-voltage driving array electrode type capillary electrophoresis chip |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006102001837A CN100561226C (en) | 2006-02-28 | 2006-02-28 | Low-voltage driving array electrode type capillary electrophoresis chip |
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| CN1844921A CN1844921A (en) | 2006-10-11 |
| CN100561226C true CN100561226C (en) | 2009-11-18 |
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| CN113758988A (en) * | 2020-05-18 | 2021-12-07 | 昆山聂尔精密仪器有限公司 | Device and method for controlling enrichment and separation of liquid-phase ions and multi-electrode chip |
| CN114660283B (en) * | 2022-05-24 | 2022-09-13 | 佛山微奥云生物技术有限公司 | Immunoassay plate type chip based on electrical acceleration and preparation method thereof |
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Granted publication date: 20091118 Termination date: 20130228 |