CN1437018A - Prepn of capillary electrophoresis chip for biochemical analysis - Google Patents
Prepn of capillary electrophoresis chip for biochemical analysis Download PDFInfo
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- CN1437018A CN1437018A CN 03111185 CN03111185A CN1437018A CN 1437018 A CN1437018 A CN 1437018A CN 03111185 CN03111185 CN 03111185 CN 03111185 A CN03111185 A CN 03111185A CN 1437018 A CN1437018 A CN 1437018A
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- raceway groove
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- capillary electrophoresis
- biochemical analysis
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Abstract
The preparation process of capillary electrophoresis chip for biochemical analysis includes selecting organic glass material, machining channels with a mechanical scoring instrument, drilling through holes in proper positions, smoothing channels and surface modification, adhering to connect two sheets of organic glass plates with organic solvent to enclose the channels. The said process of the present invention has low production cost, simple production process and high qualified product rate and is suitable for mass production.
Description
(1) technical field
That the present invention relates to is a kind of preparation method who is used for the integrated capillary electrophoretic chip of biochemical analysis.
(2) background technology
Capillary electrophoresis technique has obtained developing rapidly since the nineties, between the short several years, finish from the laboratory technique to the commercial technology, analyze biomacromolecule analysis from micromolecule, to multiple clastotype and technology, several steps from the large-scale instrument to the microminiaturization leap from simple clastotype.(integrated capillaryelectrophoresis chip is in conjunction with biotechnology, microelectric technique and MEMS technology various passages, slot electrode, detection flow cell etc. to be integrated in hypervelocity electrophoresis apparatus in the same substrate (silicon chip, glass or organic glass) ICEC) based on the integrated capillary electrophoretic chip of capillary pipe structure.Present stage, made chip adopted with glass the microelectronic processing technology process of the standard that is substrate more, i.e. photoetching → corrode → get through hole → bonding.The technological process relative complex, yield rate is low, and cost is higher relatively.
In recent years, (polymethylmethacrylate, PMMA) low with its cost, the ratio that handling ease is occupied in the capillary electrophoresis chip field is more and more big, also is the main developing direction of ICEC for organic glass.The chemical name of organic glass is polymethylmethacrylate (CH2CH3 (CO) 2CH3) n, be to be polymerized by the monomer polymethylmethacrylate, (can see through the sunshine more than 90% because its light transmission is fine, see through ultraviolet ability and reach 73%), can compare with the normal silicate unorganic glass; Organic glass is a thermoplastics, and its primary performance characteristics is in light weight, and relative density is 1.19, and its weight only is half of unorganic glass, is 43% of aluminium; Next is its physical strength height, and this is because it has the linear high polymer of side chain, and the cause of soft macromolecular chain segment is promptly arranged, and its pulling strengrth is 60～70MPa, and impact strength is 1.2～1.37MPa/cm
2, be 7～18 times of unorganic glass; At last, organic glass has certain thermotolerance, begins to soften when 140 ℃ of temperature.The method of utilizing organic glass to make the integrated capillary electrophoretic chip of biochemical analysis at present mainly contains injection moulding, tinsel impression method, silicon chip method for printing, laser ablation method.Injection moulding is to make a negative plate with the method for making of silicon chip earlier, utilizes this negative film to make the motherboard of a chromium then, utilizes this motherboard to make daughter board again, utilizes this daughter board to make mould at last again, makes many plastic chips with the method for injection moulding.Tack temperature is 105 ℃, and the time is 5 minutes, and bonding agent is that (IL), thickness is 2mm to Mylar for Top Flight Monokote, Champaign; The tinsel impression method, be to be about to be 20cm, diameter is that the two ends of the Ni-Cr alloy of 13-25 μ m are fixed on the metal bow, make it to tighten, be placed on the wide 2cm that cleans down with electrostatic prevention in advance, long 10cm, on the PMMA sheet of thick 1.6cm, also add a microslide on the tinsel, with two aluminium blocks two microslides are covered fully then, clamp aluminium block, put into stove, heating 10min in the time of 105 ℃, make tinsel after forming groove on the PMMA, take out the monoblock cooling, take down aluminium block and microslide after, transfer to tinsel, base plate and cover plate 108 ℃ bonding, time 10min; The silicon chip method for printing is that the silicon negative film that will make places between two smooth aluminium flakes, puts into the PMMA sheet that cleans down with electrostatic prevention between silicon chip and aluminium flake, clamp with aluminium flake equally then, be heated to 135 ℃, take out cooling behind the 5min, adhesion process adopts hot mode, as previously mentioned; Laser ablation method, be with high-intensity laser from the mask on the directive PMMA, moment is ablated into required shape at ad-hoc location, refers again to preceding method, and cover plate and egative film is bonding.
(3) summary of the invention
The object of the present invention is to provide that a kind of technological process is simple, the preparation method of the capillary electrophoresis chip that is used for biochemical analysis that helps improving the quality of products.
The object of the present invention is achieved like this:
(1) backing material of chip is an organic glass;
(2) organic glass is placed on little raceway groove processing machine, marks little raceway groove with delineating cutter head last of the twelve Earthly Branches on the organic glass substrate;
(3) little raceway groove is carried out surface treatment: with 2～4: 1 the methenyl choloride and the mixed solution of glacial acetic acid inject little raceway groove, little channel surface is carried out smooth treatment to solution evaporation, carrying out grafting with 5～15% acrylic acid aqueous solution handled 5-15 minute, N-methyl-silicone oil with 60～80% and 20～40% ethyl acetate mixture carry out modification to be handled 5～20 minutes, placed and carried out the ageing processing in 12～24 hours;
(4) get through the hole machining on the chip of little raceway groove, the aperture is between 0.3～2mm;
(5) chip that processing is handled well and another piece organic glass are with 5～7: the mixed solution of 1～2: 1 methenyl choloride, glacial acetic acid and ethanol carries out bonding, makes product.
The invention has the advantages that: 1, adopt organic glass as the process substrate material, being that the chip of backing material has than high performance-price ratio selecting for use of material with glass; 2, adopt machining process to carry out the processing of little raceway groove, the size of raceway groove and controllable shapes, and can change the shape of figure by demand, convenient flexibly with the photoetching graphic arts process, cost reduces greatly; 3, processing little raceway groove and get through hole technology on a slice organic glass, another does not do other processing technologys above sheet organic glass, reduced the aligning difficulty; 4, at the inner solution that injects of raceway groove, also become smooth with the volatilization channel surface of solution, improved the levelability that the raceway groove inner fluid flows, channel surface is smooth, can improve the separating effect of electrophoresis.Graft modification is carried out on the surface, reduced surface energy, improve reactionlessness.5, this preparation method does not need complicated process equipment, and machining process is simplified, and cost of manufacture reduces, processed finished products rate height.
(4) description of drawings
Fig. 1 is straight flute road chip manufacture figure among the embodiment 1;
Fig. 2 is the curved raceway groove chip manufacture figure of bent angle turning shape among the embodiment 2;
Fig. 3 is the structural representation of little raceway groove processing machine.
(4) specific embodiments
For a more detailed description to the present invention for example below:
Embodiment 1:
Present embodiment is the simple straight flute road form shown in the manuscript 1.At first organic glass is processed into needed chip size, for example 25*50mm
2, with deionized water ultrasonic cleaning surface; Carry out the processing in straight flute road with little raceway groove processing instrument.In conjunction with Fig. 3, the composition of little raceway groove processing instrument comprises pedestal 3, be installed in cutter head support 1 on the pedestal, X to worktable 6, Y to worktable 5, be installed in the sliding icking tool head 7 on the cutter head support, have Z to adjusting knob 8 on the sliding icking tool head, X has Y to adjusting knob 4 to having X on the worktable to adjusting knob 2, Y on worktable.On chip substrate, utilize little raceway groove processing instrument X-axis control transversal displacement, Y-axis control length travel, the control of Z axle is drawn and is carved the degree of depth, processes dark 30 μ m, little raceway groove of wide 100 μ m;
The organic glass chip substrate surface of drawing after carving is handled:
At first utilize 2: 1 the methenyl choloride and the mixed solution of glacial acetic acid that little channel surface is carried out smooth treatment.At the inner solution that injects of little raceway groove, also become smooth with the little channel surface of the volatilization of solution, to improve the levelability that the raceway groove inner fluid flows;
On the other hand, grafting, modification are carried out in the surface, reduce surface energy, improve reactionlessness.Concrete modification is as follows: handled 10 minutes with the acrylic acid aqueous solution of 8-10% (1).(2) with the mixture process of the ethyl acetate of 70% N-methyl-silicone oil and 30% 15 minutes; (3) ageing was placed 20～24 hours;
Behind the intact little raceway groove of processing and fabricating, on chip, punch, as sample inlet pool, buffering sample pond, waste liquid pool, sample recovery pond.Being that the drill bit of 0.5mm is got through with radius earlier, is half of the organic slide thickness of bit drills of 1.0mm with radius again, is the requirement that can satisfy plug in transfer pipet like this, and the assurance air-proof condition;
Bonding processing, carry out the sealing of raceway groove: (1) surface treatment: adopt ultrasonic cleaning, dispose 1# and 2# washing lotion respectively, adopt standard cleaning technology to carry out with electronic cleaning agent DZ-1 and DZ-2, then chip substrate is put into baking oven, under 60 ℃ of temperature, chip is dried; (2) coating of solvent: accomplish smoothly, even, otherwise can produce internal stress at interface owing to shrink inhomogeneously; (3) bonding: employing methenyl choloride etc. is done bonding agent, and two slides are bonding.
Embodiment 2
At first organic glass is processed into required chip size, for example 25*50mm
2, with deionized water ultrasonic cleaning surface;
Carry out the processing in straight flute road with little raceway groove processing instrument, on chip substrate, utilize this instrument X-axis control transversal displacement, Y-axis control length travel, the control of Z axle is drawn and is carved the degree of depth, processes dark 30 μ m, little raceway groove of wide 100 μ m;
The organic glass chip substrate surface of drawing after carving is handled:
At first utilize 3: 1 the methenyl choloride and the mixed solution of glacial acetic acid that little channel surface is carried out smooth treatment.At the inner solution that injects of little raceway groove, also become smooth with the little channel surface of the volatilization of solution, to improve the levelability that the raceway groove inner fluid flows;
On the other hand, grafting, modification are carried out in the surface, reduce surface energy, improve reactionlessness.Concrete modification is as follows: handled 15 minutes with 9% acrylic acid aqueous solution (1).(2) with the mixture process of the ethyl acetate of 60% N-methyl-silicone oil and 40% 20 minutes; (3) ageing was placed 20 hours;
Behind the intact little raceway groove of processing and fabricating, on chip, punch, as sample inlet pool, buffering sample pond, waste liquid pool, sample recovery pond.Being that the drill bit of 0.5mm is got through with radius earlier, is half of the organic slide thickness of bit drills of 1.0mm with radius again, is the requirement that can satisfy plug in transfer pipet like this, and the assurance air-proof condition;
Bonding processing, carry out the sealing of raceway groove: (1) surface treatment: adopt ultrasonic cleaning, dispose 1# and 2# washing lotion respectively, adopt standard cleaning technology to carry out with electronic cleaning agent DZ-1 and DZ-2, then chip substrate is put into baking oven, under 60 ℃ of temperature, chip is dried; (2) coating of solvent: accomplish smoothly, even, otherwise can produce internal stress at interface owing to shrink inhomogeneously; (3) bonding: employing methenyl choloride etc. is done bonding agent, and two slides are bonding.
Embodiment 3
Present embodiment is the curved raceway groove form with bent angle turning shape shown in the manuscript 2, and is basic identical with process among the embodiment 1, only raceway groove drawn the quarter program in the raceway groove process and does corresponding change.
Claims (5)
1, a kind of preparation method who is used for the capillary electrophoresis chip of biochemical analysis is characterized in that:
1.1 the backing material of chip is an organic glass;
1.2 organic glass is placed on little raceway groove processing machine, on the organic glass substrate, depicts little raceway groove with the delineation cutter head;
1.3 little raceway groove is carried out surface treatment,
1.3.1 with 2～4: 1 the methenyl choloride and the mixed solution of glacial acetic acid inject little raceway groove, little channel surface are carried out smooth treatment to solution evaporation,
Handled 5-15 minute 1.3.2 carry out grafting with 5～15% acrylic acid aqueous solution,
1.3.3 carrying out modification, N-methyl-silicone oil with 60～80% and 20～40% ethyl acetate mixture handled 5～20 minutes,
Carried out the ageing processing in 12～24 hours 1.3.4 place;
1.4 get through the hole machining on the chip of little raceway groove, the aperture is between 0.3～2mm;
1.5 the chip that processing is handled well and another piece organic glass are with 5～7: the mixed solution of 1～2: 1 methenyl choloride, glacial acetic acid and ethanol carries out bonding, makes product.
2, the preparation method who is used for the capillary electrophoresis chip of biochemical analysis according to claim 1 is characterized in that: described for the physical dimension of raceway groove is width 10～150 μ m, and the degree of depth 10～80 μ m, length is 30～300mm.
3, according to claim 1, the 2 described preparation methods that are used for the capillary electrophoresis chip of biochemical analysis, it is characterized in that: the time that described grafting is handled is 10 minutes.
4, according to claim 1, the 2 described preparation methods that are used for the capillary electrophoresis chip of biochemical analysis, it is characterized in that: the time that described modification is handled is 15 minutes.
5, the preparation method who is used for the capillary electrophoresis chip of biochemical analysis according to claim 3 is characterized in that: the time that described modification is handled is 15 minutes.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB031111858A CN1185484C (en) | 2003-03-14 | 2003-03-14 | Prepn of capillary electrophoresis chip for biochemical analysis |
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| CNB031111858A CN1185484C (en) | 2003-03-14 | 2003-03-14 | Prepn of capillary electrophoresis chip for biochemical analysis |
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| CN1185484C CN1185484C (en) | 2005-01-19 |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100417937C (en) * | 2005-01-13 | 2008-09-10 | 清华大学 | Chip type capacitance coupling contactless conductivity detector |
| CN100420622C (en) * | 2005-12-28 | 2008-09-24 | 哈尔滨工业大学 | Secondary template duplicating process method based on dimethyl silicone polymer mini component |
| CN100425984C (en) * | 2005-11-03 | 2008-10-15 | 武汉化工学院 | Method for producing miniflow control chip |
| CN100443397C (en) * | 2004-05-28 | 2008-12-17 | 哈尔滨工业大学 | Microcooling observing and controlling system and machining method thereof |
| CN102198926A (en) * | 2011-04-06 | 2011-09-28 | 哈尔滨工业大学 | Micro-channel processing method for micro-fluidic chip |
| CN103213943A (en) * | 2013-04-23 | 2013-07-24 | 山东省科学院海洋仪器仪表研究所 | Method for processing and leveling micro-channel of polymer chip |
| US8844782B2 (en) | 2010-07-16 | 2014-09-30 | Corning Incorporated | Methods for scribing and separating strengthened glass substrates |
| US8875967B2 (en) | 2010-03-19 | 2014-11-04 | Corning Incorporated | Mechanical scoring and separation of strengthened glass |
| US10351460B2 (en) | 2012-05-22 | 2019-07-16 | Corning Incorporated | Methods of separating strengthened glass sheets by mechanical scribing |
| US10386854B2 (en) | 2014-02-07 | 2019-08-20 | Crown Equipment Corporation | Systems, methods, and mobile client devices for supervising industrial vehicles |
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2003
- 2003-03-14 CN CNB031111858A patent/CN1185484C/en not_active Expired - Fee Related
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100443397C (en) * | 2004-05-28 | 2008-12-17 | 哈尔滨工业大学 | Microcooling observing and controlling system and machining method thereof |
| CN100417937C (en) * | 2005-01-13 | 2008-09-10 | 清华大学 | Chip type capacitance coupling contactless conductivity detector |
| CN100425984C (en) * | 2005-11-03 | 2008-10-15 | 武汉化工学院 | Method for producing miniflow control chip |
| CN100420622C (en) * | 2005-12-28 | 2008-09-24 | 哈尔滨工业大学 | Secondary template duplicating process method based on dimethyl silicone polymer mini component |
| US9802854B2 (en) | 2010-03-19 | 2017-10-31 | Corning Incorporated | Mechanical scoring and separation of strengthened glass |
| US8875967B2 (en) | 2010-03-19 | 2014-11-04 | Corning Incorporated | Mechanical scoring and separation of strengthened glass |
| US8844782B2 (en) | 2010-07-16 | 2014-09-30 | Corning Incorporated | Methods for scribing and separating strengthened glass substrates |
| US8864005B2 (en) | 2010-07-16 | 2014-10-21 | Corning Incorporated | Methods for scribing and separating strengthened glass substrates |
| US9611167B2 (en) | 2010-07-16 | 2017-04-04 | Corning Incorporated | Methods for scribing and separating strengthened glass substrates |
| CN102198926A (en) * | 2011-04-06 | 2011-09-28 | 哈尔滨工业大学 | Micro-channel processing method for micro-fluidic chip |
| US10351460B2 (en) | 2012-05-22 | 2019-07-16 | Corning Incorporated | Methods of separating strengthened glass sheets by mechanical scribing |
| CN103213943A (en) * | 2013-04-23 | 2013-07-24 | 山东省科学院海洋仪器仪表研究所 | Method for processing and leveling micro-channel of polymer chip |
| CN103213943B (en) * | 2013-04-23 | 2015-08-05 | 山东省科学院海洋仪器仪表研究所 | A kind of processing of polymer chip microchannel and leveling method |
| US10386854B2 (en) | 2014-02-07 | 2019-08-20 | Crown Equipment Corporation | Systems, methods, and mobile client devices for supervising industrial vehicles |
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