CN103585943A - Micro-reactor suitable for micro-liquid mixing and biochemical reaction and manufacturing method thereof - Google Patents
Micro-reactor suitable for micro-liquid mixing and biochemical reaction and manufacturing method thereof Download PDFInfo
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- CN103585943A CN103585943A CN201310524165.4A CN201310524165A CN103585943A CN 103585943 A CN103585943 A CN 103585943A CN 201310524165 A CN201310524165 A CN 201310524165A CN 103585943 A CN103585943 A CN 103585943A
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Abstract
The invention discloses a micro-reactor suitable for micro-liquid mixing and biochemical reaction and a manufacturing method thereof. The micro-reactor comprises an upper cover plate and a lower base plate which is butted with the upper cover plate. A piezoelectric film is arranged between the lower base plate and the upper cover plate. The piezoelectric film is provided with a micro channel, an outlet and an inlet of which are respectively corresponding to a liquid outlet and a liquid inlet of the upper cover plate. A surface acoustic wave generator is also arranged between the lower base plate and the piezoelectric film. According to the invention, a temperature control system is integrated into the micro-reactor such that a reaction in the micro-reactor can be conducted under the condition of constant temperature. By the mechanism of surface acoustic wave, mechanical vibration can be generated to drive non-charged liquids to be mixed, and an alternating electric field also will be generated on an energy transducer. Thus, the micro-reactor is endowed with a liquid vibration function by surface acoustic wave, a liquid driving function by the alternating electric field and a microenvironment temperature control function, and efficiency of a micro-liquid chemiluminiscence reaction can be raised greatly. Therefore, the structure also has a wider application range, and will have a more obvious effect of driving charged liquids.
Description
Technical field
The invention belongs to liquid reactor field, be specifically related to a kind of microreactor and manufacture method thereof that is applicable to micro liquid mixing biochemical reaction.
Background technology
Application minute manufacturing technology, is integrated in the functions such as the mixing of chemical sample, reaction, detection in small volume, forms micro-fluidic laboratory, can realize microminiaturization and the cost degradation of biochemistry detection system.Microfluid based Lab on a chip is called again chip lab, is the operations such as chemistry and a sample preparation related in biological field, reaction, separated, detection and cell cultivation, separation, cracking are integrated on chip.In a micro-fluidic chip, the material that we were concerned about and handled normally exists with liquid (neat liquid solution or suspension etc.) form, for the research of biology, chemistry and related discipline, the interaction of autotelic these liquid of control is the keys that realize chip lab function.For a variety of methods that improved mixed effect people after deliberation, as promoted the mixing between fluid by magnetic field, electric field and sound field etc.But these devices can only be applicable to charged fluid, the having relatively high expectations of convection cell.
Summary of the invention
The object of the invention is to address the above problem, a kind of microreactor and manufacture method thereof that is applicable to micro liquid mixing biochemical reaction is provided, this reactor adopts surface acoustic wave to improve mixing usefulness, film resistor heating arrangement, temperature detecting resistance and film cooling device form closed-loop system, can the abundant mixing of realization response liquid and the accurate control of reaction temperature.
In order to reach above object, the present invention is achieved by the following technical solutions:
Be applicable to a microreactor for micro liquid mixing biochemical reaction, comprise upper cover plate and the lower shoe connecting with upper cover plate; On upper cover plate, offer liquid inlet and liquid outlet, liquid inlet and liquid outlet are separately positioned on the both sides of temperature control structure; Between lower shoe and upper cover plate, be provided with piezoelectric membrane, on piezoelectric membrane, be provided with fluid channel; The outlet of fluid channel is corresponding with liquid outlet and liquid inlet on upper cover plate respectively with entrance; Between lower shoe and piezoelectric membrane, be also provided with surface acoustic wave generating means, in the vertical direction, piezoelectric membrane covers surface acoustic wave generating means.
The inner side of described upper cover plate is provided with for controlling the temperature control structure of micro fluid reaction regional temperature in fluid channel, and temperature control structure is right against fluid channel.
Described temperature control structure is two groups of temperature-controlled arrays that structure is identical that layering cover is engraved in upper cover plate inner surface; Wherein, each group temperature-controlled array comprises heating film resistor, a temperature-measuring thin film resistance and a cooling film; Heating film resistor, temperature-measuring thin film resistance and cooling film replace the temperature control system that arrayed forms a closed loop.
Described heating film resistor and the material of temperature-measuring thin film resistance are metal material; Cooling film is the cooling film of semiconductor or ferroelectric thin film.
Described fluid channel is Y type passage, and two branch's one sides of Y type passage are entrance, and opposite side is outlet; Wherein two entrances of branch's one side are corresponding with two liquid inlets on upper cover plate, and the outlet of opposite side is corresponding with the liquid outlet on upper cover plate.
Described surface acoustic wave generating means is the interdigital transducer on lower shoe by sputter or wet etching, and interdigital transducer adopts aluminum metal thin-film material to make.
On described interdigital transducer, be provided with two for the pad of external wire.
Described upper cover plate is that PDMS is dull and stereotyped, and lower shoe adopts silicon chip as substrate.
Lithium niobate piezoelectric membrane or the zno piezoelectric thin film of described piezoelectric membrane for adopting film growth techniques to grow in substrate.
A manufacture method for the microreactor of micro liquid mixing biochemical reaction, comprises the following steps:
1) adopt PDMS material to make PDMS flat board as upper cover plate, then adopt MEMS technique two groups of the inner side of upper cover plate layering alignments by the temperature-controlled array that heats film resistor, temperature-measuring thin film resistance and cooling film and form, each group temperature-controlled array comprises heating film resistor, a temperature-measuring thin film resistance and a cooling film; Heating film resistor, temperature-measuring thin film resistance and cooling film replace the temperature control system that arrayed forms a closed loop; Finally upper cover plate is offered liquid inlet and liquid outlet again;
2) adopt silicon chip as substrate fabrication lower shoe, first, on lower shoe by interdigital transducer on sputter or wet etching; Then, the lithium niobate piezoelectric membrane or the zno piezoelectric thin film that adopt film growth techniques to grow in substrate; Finally, adopt observing and controlling sputtering technology or wet-etching technology in MEMS technique on piezoelectric membrane, to produce fluid channel, wherein the entrance and exit of fluid channel is corresponding with liquid inlet and liquid outlet on upper cover plate respectively;
3) will after upper cover plate and lower shoe docking, form the complete microreactor that is applicable to micro liquid mixing biochemical reaction.
Compared with prior art, the present invention has following beneficial effect:
The present invention is applicable to the microreactor of micro liquid mixing biochemical reaction, and first, the present invention combines surface acoustic wave vibration and alternating electric field, so not only can strengthen the effect of driving, and can widen range of application of the present invention.In biochemical reaction, major part is to take to be in contact with one another reaction as main between reactive liquid solution and particle.The present invention not only can drive charged liquid and with the mixing of a liquid, not promote the generation of micro-reaction, but also can be for electrified particle and charged particle not, and the gathering that promotes particle makes the detection reaction in reactor can sufficient reacting with separated; Secondly, the present invention is placed on surface acoustic wave generating means between piezoelectric membrane and lower shoe, what make that surface acoustic wave generating means is arranged in microreactor has below avoided sound wave and voltage in the loss of communication process, has strengthened the driving effect of piezoelectric to microreactor.Between surface acoustic wave generating means and fluid channel, by piezoelectric membrane, isolated simultaneously, therefore can arrange according to concrete demand the surface acoustic wave generating means of various shapes; Finally, the present invention combines temperature field, sound field and electric field, for biochemical reaction provides a stable isoperibol.In chemical reaction, have one to make the fastest temperature of chemical reaction velocity, and reaction temperature when different the product of some reaction also different.In biological respinse and testing process, because bioactive requirement is stricter to the requirement of temperature.Owing to being that surface acoustic wave or electric field all can produce heat in acting on the process of fluid in the present invention, affect reaction temperature.Therefore the present invention is integrated into temperature control system in invention, is that the reaction in microreactor can occur under the condition of a constant temperature.So, the present invention is in surface acoustic wave mechanism, not only can produce mechanical oscillation drives non-charged fluid to mix, at transducer upside, also can produce AC field simultaneously, make the present invention drive function and microenvironment temp. control function with surface acoustic wave vibration liquid functional and alternating electric field, can greatly improve the usefulness of micro liquid chemiluminescence reaction, so this structure also has, and range of application is more obvious for the driving effect meeting of charged fluid more widely.
Further, the temperature control structure of upper cover plate of the present invention inner side is array distribution, can effectively realize homogeneous temperature field in fluid channel.
Further, the present invention is provided with the pad for external wire on interdigital transducer, excite the signal of surface acoustic wave to be passed in transducer by pad place, in lower shoe, piezoelectric membrane is subject to can producing vibration after alternating voltage effect, and propagate vibration, Vibration propagation drives Microfluidic Mixing in fluid channel.
The present invention is applicable to the manufacture method of the microreactor of micro liquid mixing biochemical reaction, and upper cover plate is selected PDMS material, makes PDMS flat board, then adopts MEMS technique layering alignment heating film resistor, temperature-measuring thin film resistance and refrigeration ferroelectric thin film.Lower shoe adopts silicon chip as base, first on base, by sputter or wet etching, obtains interdigital transducer, then adopts film growth techniques in substrate, grow lithium niobate or zno piezoelectric thin film; Finally adopt in MEMS technique observing and controlling sputtering technology or wet-etching technology to produce fluid channel on lithium niobate film.These devices and electronic circuit can integratedly be manufactured, and convenient signal treatment is easily gone, and controllability is good.
Accompanying drawing explanation
The overall structure schematic diagram of Fig. 1 microreactor of the present invention;
The structural representation of Fig. 2 upper cover plate of the present invention inner side;
The structural representation of Fig. 3 lower shoe of the present invention.
Wherein, 1 is upper cover plate; 2 is lower shoe; 3 is piezoelectric membrane; 4 is liquid inlet; 5 is liquid outlet; 6 is fluid channel; 7 is surface acoustic wave generating means; 8 is heating film resistor; 9 is temperature-measuring thin film resistance; 10 is cooling film; 11 is pad.
The specific embodiment
Below in conjunction with drawings and Examples, the present invention is described in further detail.
Referring to Fig. 1 to Fig. 3, a kind of microreactor that is applicable to micro liquid mixing biochemical reaction of the present invention, comprises upper cover plate 1 and the lower shoe 2 connecting with upper cover plate 1, and wherein, upper cover plate 1 is that PDMS is dull and stereotyped, and lower shoe 2 adopts silicon chip as substrate; On upper cover plate 1, offer liquid inlet 4 and liquid outlet 5, liquid inlet 4 and liquid outlet 5 are separately positioned on the both sides of temperature control structure.The inner side of upper cover plate 1 is provided with for controlling the temperature control structure of the interior micro fluid reaction regional temperature of fluid channel 6, and temperature control structure is right against fluid channel 6.Temperature control structure is two groups of temperature-controlled arrays that structure is identical that layering cover is engraved in upper cover plate 1 inner surface; Wherein, each group temperature-controlled array comprises a heating film resistor 8, temperature-measuring thin film resistance 9 and a cooling film 10; Heating film resistor 8, temperature-measuring thin film resistance 9 and cooling film 10 be the temperature control system of a closed loop of arrayed composition alternately.The material of heating film resistor 8 and temperature-measuring thin film resistance 9 is metal material, adopts the materials such as platinum, aluminium, copper to make; Cooling film 10 is the cooling film of semiconductor or ferroelectric thin film.Between lower shoe 2 and upper cover plate 1, be provided with piezoelectric membrane 3, on piezoelectric membrane 3, be provided with fluid channel 6, lithium niobate piezoelectric membrane or the zno piezoelectric thin film of piezoelectric membrane 3 for adopting film growth techniques to grow in substrate; Fluid channel 6 is Y type passage, and two branch's one sides of Y type passage are entrance, and opposite side is outlet; Wherein two entrances of branch's one side are corresponding with two liquid inlets on upper cover plate 1, and the outlet of opposite side is corresponding with the liquid outlet 5 on upper cover plate 1.Between lower shoe 2 and piezoelectric membrane 3, be also provided with surface acoustic wave generating means 7, in the vertical direction, piezoelectric membrane 3 covers surface acoustic wave generating means 7, surface acoustic wave generating means 7 is the interdigital transducer on lower shoe 2 by sputter or wet etching, interdigital transducer adopts aluminum metal thin-film material to make, and is provided with two for the pad 11 of external wire on interdigital transducer.
The invention also discloses a kind of manufacture method that is applicable to the microreactor of micro liquid mixing biochemical reaction, comprise the following steps:
1) adopt PDMS material to make PDMS flat board as upper cover plate 1, then adopt MEMS technique two groups of the inner side of upper cover plate 1 layering alignments by the temperature-controlled array that heats film resistor, temperature-measuring thin film resistance and cooling film 10 and form, each group temperature-controlled array comprises a heating film resistor 8, temperature-measuring thin film resistance 9 and a cooling film 10; Heating film resistor 8, temperature-measuring thin film resistance 9 and cooling film 10 be the temperature control system of a closed loop of arrayed composition alternately; Finally upper cover plate 1 is offered liquid inlet 4 and liquid outlet 5 again;
2) adopt silicon chip as substrate fabrication lower shoe 2, first, on lower shoe 2 by interdigital transducer on sputter or wet etching; Then, the lithium niobate piezoelectric membrane or the zno piezoelectric thin film that adopt film growth techniques to grow in substrate; Finally, adopt observing and controlling sputtering technology or wet-etching technology in MEMS technique on piezoelectric membrane, to produce fluid channel 6, wherein the entrance and exit of fluid channel 6 is corresponding with liquid inlet 4 and liquid outlet 5 on upper cover plate 1 respectively;
3) will after upper cover plate 1 and lower shoe 2 docking, form the complete microreactor that is applicable to micro liquid mixing biochemical reaction.
As shown in Figure 1 to Figure 3, the present invention is comprised of upper cover plate and two platy structures of lower shoe.As shown in Figure 2, upper cover plate adopts PDMS material, and outside is designed with two alcove structures, and three through holes; The temperature control structure of upper cover plate inner side, is arrayed, adopts MEMS technique to make structure of controlling temperature.As shown in Figure 3: lower shoe be take silicon chip as substrate, adopt MEMS technique to make surface acoustic wave generating means above.In the vertical direction, piezoelectric membrane covers interdigital transducer, finally on piezoelectric membrane, etches fluid channel, the position of the position corresponding cover plate Y type passage of surface acoustic wave generating means.Upper cover plate and lower shoe are bonded to and are integrated, and form microreactor.The structure of controlling temperature of upper cover plate inner side, is comprised of heating film resistor, temperature-measuring thin film resistance and cooling ferroelectric thin film, is MEMS process film layer, and wherein heating resistor and temperature detecting resistance are metal platinum, and cooling film is ferroelectric material.As shown in Figure 3, the interdigital transducer on lower shoe is to make by the magnetron sputtering in MEMS technique or wet-etching technology, and material is metallic aluminium, also can utilize the replacements such as metallic copper, platinum.Piezoelectric membrane in lower shoe is made by film growth techniques, and material is lithium niobate, also can replace with piezoelectrics such as zinc oxide.
The course of work of the present invention is such:
When using microreactor, the lead-in wire by interdigital electrode 7 adds sinusoidal alternating voltage signal in advance, produces stable mechanical wave in fluid channel cavity.Lead-in wire by heating arrangement and cooling structure is communicated with current signal in advance, and be connected to external equipment the real time measure microenvironment temperature by the lead-in wire of temperature measurement structure, through control algolithm, determine heating voltage signal magnitude, realize the accurate temperature of fluid channel Mixed Zone and control.
Reactor of the present invention can be realized the abundant mixing of two kinds of micro-biochemistry liquid, and can accurately control the temperature of reaction, can greatly strengthen biochemical reaction usefulness.Invention comprises microreactor system architecture layout.Surface acoustic wave recurring structure, temperature control device, system control method.Microreactor system architecture layout comprises upper and lower two platy structures, upper cover plate is made gateway and the temperature control device of fluid channel, lower shoe is comprised of four parts, the bottom is that silicon base is used for supporting whole micro-fluidic chip, the circular interdigital transducer of sputter in silicon base, then in silicon base, grow lithium niobate or zno piezoelectric thin film finally etch fluid channel on piezoelectric membrane.Finally upper and lower bottom plate bonding just can be obtained to the micro-mixer needing.Surface acoustic wave recurring structure produces stable mechanical oscillation in liquid Mixed Zone, acts on micro-liquid it is fully mixed.If micro-liquid is charged liquid, in surface acoustic wave recurring structure, excite the AC field of mechanical oscillation can drive the charged ion (particle) in liquid simultaneously, promote the mixing of micro-liquid.Shown in can the realize ± local ambient temperature of 1 ℃ of film temperature control device accurately control.Meet micro-biochemical reaction required.Described system control method comprises surface acoustic wave pumping signal form, temperature control signals form, and micro liquid injects and outflow mode.Upper cover plate material is glass or PDMS or quartz.Cover plate material is identical with upper cover plate material.The base material of lower shoe is lithium niobate crystal chip, and surface acoustic wave structure is metallic film material, and tepor control device is respectively temperature detecting resistance film, heating resistor film, the cooling film of semiconductor or ferroelectric thin film.
Claims (10)
1. a microreactor that is applicable to micro liquid mixing biochemical reaction, is characterized in that: comprise upper cover plate (1) and the lower shoe (2) connecting with upper cover plate (1); On upper cover plate (1), offer liquid inlet (4) and liquid outlet (5), liquid inlet (4) and liquid outlet (5) are separately positioned on the both sides of temperature control structure; Between lower shoe (2) and upper cover plate (1), be provided with piezoelectric membrane (3), on piezoelectric membrane (3), be provided with fluid channel (6); The outlet of fluid channel (6) and entrance are corresponding with liquid outlet (5) and liquid inlet (4) on upper cover plate (1) respectively; Between lower shoe (2) and piezoelectric membrane (3), be also provided with surface acoustic wave generating means (7), in the vertical direction, piezoelectric membrane (3) covers surface acoustic wave generating means (7).
2. the microreactor that is applicable to micro liquid mixing biochemical reaction according to claim 1, it is characterized in that: the inner side of described upper cover plate (1) is provided with for controlling the temperature control structure of the interior micro fluid reaction regional temperature of fluid channel (6), and temperature control structure is right against fluid channel (6).
3. the microreactor that is applicable to micro liquid mixing biochemical reaction according to claim 2, is characterized in that: described temperature control structure is two groups of temperature-controlled arrays that structure is identical that layering cover is engraved in upper cover plate (1) inner surface; Wherein, each group temperature-controlled array comprises heating film resistor (8), a temperature-measuring thin film resistance (9) and a cooling film (10); Heating film resistor (8), temperature-measuring thin film resistance (9) and cooling film (10) be the temperature control system of a closed loop of arrayed composition alternately.
4. the microreactor that is applicable to micro liquid mixing biochemical reaction according to claim 3, is characterized in that: described heating film resistor (8) and the material of temperature-measuring thin film resistance (9) are metal material; Cooling film (10) is the cooling film of semiconductor or ferroelectric thin film.
5. according to the microreactor that is applicable to micro liquid mixing biochemical reaction described in claim 1,2,3 or 4, it is characterized in that: described fluid channel (6) is Y type passage, and two branch's one sides of Y type passage are entrance, opposite side is outlet; Wherein two entrances of branch's one side are corresponding with two liquid inlets on upper cover plate (1), and the outlet of opposite side is corresponding with the liquid outlet (5) on upper cover plate (1).
6. the microreactor that is applicable to micro liquid mixing biochemical reaction according to claim 1 and 2, it is characterized in that: described surface acoustic wave generating means (7) is the interdigital transducer on lower shoe (2) by sputter or wet etching, and interdigital transducer adopts aluminum metal thin-film material to make.
7. the microreactor that is applicable to micro liquid mixing biochemical reaction according to claim 6, is characterized in that: on described interdigital transducer, be provided with two pads for external wire (11).
8. the microreactor that is applicable to micro liquid mixing biochemical reaction according to claim 1 and 2, is characterized in that: described upper cover plate (1) is dull and stereotyped for PDMS, and lower shoe (2) adopts silicon chip as substrate.
9. the microreactor that is applicable to micro liquid mixing biochemical reaction according to claim 1, is characterized in that: lithium niobate piezoelectric membrane or the zno piezoelectric thin film of described piezoelectric membrane (3) for adopting film growth techniques to grow in substrate.
10. a manufacture method that is applicable to the microreactor of micro liquid mixing biochemical reaction, is characterized in that, comprises the following steps:
1) adopt PDMS material to make PDMS flat board as upper cover plate (1), then adopt MEMS technique two groups of the inner side layering alignments of upper cover plate (1) by the temperature-controlled array that heats film resistor, temperature-measuring thin film resistance and cooling film (10) and form, each group temperature-controlled array comprises heating film resistor (8), a temperature-measuring thin film resistance (9) and a cooling film (10); Heating film resistor (8), temperature-measuring thin film resistance (9) and cooling film (10) be the temperature control system of a closed loop of arrayed composition alternately; Finally upper cover plate (1) is offered liquid inlet (4) and liquid outlet (5) again;
2) adopt silicon chip as substrate fabrication lower shoe (2), first, interdigital transducer on lower shoe (2) is gone up by sputter or wet etching; Then, the lithium niobate piezoelectric membrane or the zno piezoelectric thin film that adopt film growth techniques to grow in substrate; Finally, adopt observing and controlling sputtering technology or wet-etching technology in MEMS technique on piezoelectric membrane, to produce fluid channel (6), wherein the entrance and exit of fluid channel (6) is corresponding with liquid inlet (4) and liquid outlet (5) on upper cover plate (1) respectively;
3) will after upper cover plate (1) and lower shoe (2) docking, form the complete microreactor that is applicable to micro liquid mixing biochemical reaction.
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| CN110404490A (en) * | 2019-07-31 | 2019-11-05 | 山东豪迈机械制造有限公司 | A kind of layering mixing microreactor |
| CN110404490B (en) * | 2019-07-31 | 2024-05-03 | 山东豪迈机械制造有限公司 | Layered mixing microreactor |
| CN110632138A (en) * | 2019-11-01 | 2019-12-31 | 江南大学 | Interdigital electrode chip |
| CN112403413A (en) * | 2020-09-29 | 2021-02-26 | 合肥通用机械研究院有限公司 | Integrated countercurrent strengthening microreactor |
| CN114675686A (en) * | 2022-03-18 | 2022-06-28 | 长江存储科技有限责任公司 | Temperature control system and temperature control method for multi-chamber |
| CN114675686B (en) * | 2022-03-18 | 2023-06-13 | 长江存储科技有限责任公司 | Temperature control system and temperature control method for multiple chambers |
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