CN103586094A - Micro-fluidic chip with circulation mixed structure and circulation mixed method - Google Patents
Micro-fluidic chip with circulation mixed structure and circulation mixed method Download PDFInfo
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- CN103586094A CN103586094A CN201310650243.5A CN201310650243A CN103586094A CN 103586094 A CN103586094 A CN 103586094A CN 201310650243 A CN201310650243 A CN 201310650243A CN 103586094 A CN103586094 A CN 103586094A
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Abstract
The invention provides a micro-fluidic chip with a circulation mixed structure and a circulation mixed method. A plurality of prestored micro-channel structures are manufactured on the chip, different prestored channels are separated through micro electromagnetic valves, after reaction fluid is stored in the channels of the chip according to a preset proportion, the micro electromagnetic valves are opened, premixed solutions are connected to form a sealed loop, and the sealed loop is connected with a micro piezoelectric pump or a micro peristaltic pump through microchips of the channels to be used as a driving force source for dynamic mixing. The mixing ratios of different mixed solutions are controlled according to the lengths of the micro-channels on the chip and the dead volume of connecting elements, parameters of the varieties of the mixed solutions, the amount of the solutions and the mixed ratios of the solutions are preset, the sample introduction step of the solutions does not need to be synchronously conducted in real time, and the solutions can be more easily replaced. After being mixed, the mixed solutions can be guided to a storage structure on a follow-up chip structure for conducting multi-step reaction, and complex systems can suitably react on the chip.
Description
Technical field
The invention belongs to microfluidic chip analysis technical field, concrete a kind of micro-fluidic chip and circulation mixed method with circulation mixed structure.
Background technology
Microflow control technique is based on micro electronmechanical processing (MEMS) technology, and micro-fluidic chip is by construct organic network with microchannel on the chip of small size, thereby makes controlled fluid run through whole system, in order to replace the function of conventional chemical and biology laboratory.Because it is efficient, quick, reagent dosage is few, the advantages such as low cost and high integration, be subject to domestic and international researcher expert's extensive concern, and in pollutant monitoring, life science, good application prospect has been shown in the fields such as medical treatment & health, has promoted analytical instrument to portable, miniature, integrated development simultaneously.
The controllable operating of microfluid is that micro-fluidic chip technology realizes the applicable core of its merit, but due to the restriction of micro-technology of preparing, at chip body, fastens the micro-valve body of integrated Micropump system also in conceptual phase, and cannot using widely.On chip, realize at present the ratio of solution and mix the general real-time mixed mode of mechanical type syringe pump that adopts, need being used in conjunction with of a plurality of micro-sampling pumps, for reaction system long-time, multi-step, lack adaptability.And Minitype electromagnetic valve, the equipment such as check-valves, piezoelectric pump becomes a kind of transition means of microfluidic control in micro-fluidic chip in this period, and for the practical application of micro-fluidic chip brought may, for the miniaturization microminiaturization of analytical instrument provides new research direction.Yet due to the impact that stability and the system of external Small electronic component are received external environment, the mixing of microfluid in chip channel cannot be by the direct control simple realization of extraneous electronic devices and components.Needing reasonably by design with external little, channel system that micropump valve body system matches and suitable flow passage structure, is to solve microchip fluid to control, and promotes chip technology practical application process.
Summary of the invention
The object of the invention is to propose a kind of micro-fluidic chip and circulation mixed method with circulation mixed structure, described micro-fluidic chip can be preset and mix when multi-step and mix multiple reactant.
For achieving the above object, the present invention adopts following technical proposals to be achieved:
A kind of micro-fluidic chip with circulation mixed structure, described micro-fluidic chip is provided with circulation mixed cell, described circulation mixed cell comprises chip channel and is located at the first electric hybrid module in chip channel, described the first electric hybrid module comprises two liquid storage passages, two sample intake passages, import magnetic valve and connection magnetic valve, described two sample intake passages are located between two liquid storage passages, on described two sample intake passages, be connected with respectively two import magnetic valves controlling its switch, between two sample intake passages, be also provided with and control the connection magnetic valve that two sample intake passages are communicated with, in described chip channel, be also provided with minitype piezoelectric pump and sample output passage, by outlet solenoid control, it closes described sample output passage.
Further, described micro-fluidic chip comprises multi-stage circulating mixed cell, and the exit passageway of previous stage circulation mixed cell is connected successively with the sample intake passage of the circulation mixed cell of rear one-level.
The present invention also provides the another kind of micro-fluidic chip with circulation mixed structure, and described micro-fluidic chip is provided with chip channel, and described chip channel is provided with the first electric hybrid module and at least one second electric hybrid module described in the claim 1 connecting successively;
Described the second electric hybrid module comprises the liquid storage passage being located in chip channel, a sample intake passage, sample output passage and be communicated with magnetic valve, the sample intake passage of described the second electric hybrid module and sample output passage are between the liquid storage passage of the first electric hybrid module and the liquid storage passage of the second electric hybrid module, sample intake passage and sample output passage are also connected with respectively the magnetic valve of controlling its switch, between sample intake passage and sample output passage, be also provided with the connection magnetic valve of controlling two channel connections, in described chip channel, be also provided with minitype piezoelectric pump and sample output passage, by outlet solenoid control, it closes described sample output passage.
Described magnetic valve and piezoelectric pump are and are coupled on micro-fluidic chip.
The circulation mixed method of the described micro-fluidic chip with circulation mixed structure, it comprises the following steps: the magnetic valve of controlling the first component sample introduction is opened, after the first component sample introduction completes, controlling the magnetic valve of second component sample introduction opens, second component sample introduction mixes with the first component, the various components of sample introduction are until all components sample introduction completes successively in order, and various components mixing are reacted.
The circulation mixed method of the described micro-fluidic chip with circulation mixed structure, it comprises the following steps: the magnetic valve of controlling the first component sample introduction is opened, after the first component sample introduction completes, controlling the magnetic valve of second component sample introduction opens, after second component sample introduction and the first component hybrid reaction complete, the product of the first component and the second component is mixed and is reacted with the 3rd component, and so sample introduction is until all components sample introduction having reacted.
Compared with prior art, advantage of the present invention and good effect are: the present invention prepares a plurality of pre-stored MCAs on chip, different pre-stored interchannels utilizes the miniature electromagnetic valve of closed condition spaced apart, when reacting fluid completes after storage by preset ratio in chip channel, open the miniature electromagnetic valve of closed condition, aqueous premix is connected to form to closed loop and dynamically mixes as drive force source by passage microchip connection minitype piezoelectric pump or miniature peristaltic pump.After having mixed, mixed solution can be imported on follow-up chip structure to storage organization and carry out multi-step reaction.
Chip hybrid mode of the present invention is carried out two or more reacting fluid pre-stored by the open and-shut mode of miniature electromagnetic valve control chip microchannel on chip, controls the mixing ratio of different mixed solutions by the length of microchannel on chip and the dead volume of Connection Element.Can be according to concrete chemical reaction system to the kind to mixed solution, amount of solution, the parameters such as the mixing ratio of solution pre-set, and the sample introduction step of solution is carried out without real-time synchronization, changes more easily reality of the operations such as solution.By miniature electromagnetic valve, control and form after loop, using minitype piezoelectric pump or miniature peristaltic pump as the driving mixing of inner drive source, increased the operability of fluid, avoided current chip to be blended in chip structure and cannot efficiently mix the shortcoming that can only take static mixing in situation completely.Formation and separation by a plurality of circulation around circuit structures of solenoid control can be reacted according to concrete reaction needed control multi-step, are adapted to complex system and on chip, react realization.
Read by reference to the accompanying drawings after the specific embodiment of the present invention, it is clearer that the other features and advantages of the invention will become.
Accompanying drawing explanation
Fig. 1 is the microfluidic chip structure schematic diagram that in the embodiment of the present invention 1, two component solution circulation mix.
Fig. 2 is the microfluidic chip structure schematic diagram that in the embodiment of the present invention 1, single stage Multi component circulation mixes.
Fig. 3 is the microfluidic chip structure schematic diagram that in the embodiment of the present invention 1, multi-step Multi component circulation mixes.
In figure: the sample intake passage that A1-A4 is different solutions; B1-B2 is solution sample output passage; C1-C4 is liquid storage passage on chip; V1-V7 is the miniature electromagnetic valve being coupled on chip; E1-E2 is the minitype piezoelectric pump being coupled on chip.
The specific embodiment
Below in conjunction with the drawings and specific embodiments, technical scheme of the present invention is described in further detail.
Embodiment 1
Be the micro-fluidic chip consisting of single circulation mixed cell as shown in Figure 1, the present embodiment is to utilize structure shown in Fig. 1 to carry out the pattern that two component solution circulation mix.
As shown in Figure 1, micro-fluidic chip of the present invention is provided with circulation mixed cell, described circulation mixed cell comprises chip channel T and is located at the first electric hybrid module in chip channel, described the first electric hybrid module comprises two liquid storage passages, two sample intake passages, import magnetic valves and is communicated with magnetic valve, described two sample intake passages are located between two liquid storage channel C 1, C2, and liquid storage passage on chip together determines the mixing ratio of component with the dead volume that is coupled in the elements such as magnetic valve on chip, piezoelectric pump.(A1 is the first sample intake passage to described two sample intake passages, A2 is the second sample intake passage) on be connected with respectively two import magnetic valves controlling its switch, first magnetic valve of V1 for controlling the first sample intake passage folding and closing, second magnetic valve of V2 for controlling the second sample intake passage folding and closing, between described the first sample intake passage A1 and the second sample intake passage A2, be also connected with the connection magnet valve V3 that controls two passage foldings and close, the open and-shut mode of V3 determines that the contact of component mixes; In described chip channel, be also provided with minitype piezoelectric pump E1 and sample output passage B, described sample output passage is controlled it by outlet magnetic valve V4 and is closed, and minitype piezoelectric pump E1 makes piezoelectric vibrator generation deformation energy drive inner fluid passage to flow by the inverse piezoelectric effect of piezoelectric ceramics.
Can with miniature check valve, partly replace magnetic valve as required in actual applications;
The circulation that the present embodiment completes two components according to the following steps mixes:
(1) the first magnetic valve V1 being coupled on micro-fluidic chip opens, the second magnetic valve V2 closes, and the 3rd magnetic valve V3 opens, and the 4th magnetic valve V4 opens, minitype piezoelectric pump E1 closes, and by the first sample intake passage A1 sample introduction component 1, will be full of C1, C2 and be flowed out from B outlet;
(2) described V1 closes, and described V2 opens, and described V3 closes, and described V4 opens, and described E1 closes, and by the second sample intake passage A2 sample introduction component 2, will be full of C2 and be flowed out from B outlet;
(3) described V1 closes, and described V2 closes, and described V3 opens, and described V4 closes, and described E1 opens, and chip internal will form the ring structure of sealing, and under the driving of E1, component 1,2 is mixed.This kind of mixed mode can be avoided being coupled in the dead volume of components and parts and retain the impact of solution on reaction system.
The impact that original paper causes if be coupled in application system is little, and applying step can be reduced to: (1) V1 opens, and V2 opens, and V3 closes, and V4 opens, and E1 closes, and A1, A2 while sample introduction also flows out from B outlet; (2) V1 closes, and V2 closes, and V3 opens, and V4 closes, and E1 opens, and chip internal will form the ring structure of sealing, and under the driving of E1, component 1,2 is mixed.Chip need to clean with distilled water before enabling, and guarantees in passage, there is no obvious bubble (will the affecting the operating efficiency of piezoelectric pump of bubble).
Embodiment 2
Be by plural circulation mixed cell micro-fluidic chip in series as shown in Figure 2, the present embodiment is to utilize structure shown in Fig. 2 to carry out the pattern that single stage Multi component circulation mixes.
As shown in Figure 2, described micro-fluidic chip is provided with chip channel T, and described chip channel is provided with successively the first electric hybrid module and at least one second electric hybrid module described in an embodiment 1 who connects.
Described the second electric hybrid module comprises the liquid storage channel C 3 being located in chip channel, a sample intake passage A3, sample output passage B1 and be communicated with magnetic valve V7, the sample intake passage A3 of described the second electric hybrid module and sample output passage B1 are between the liquid storage channel C 2 of the first electric hybrid module and the liquid storage channel C 3 of the second electric hybrid module, sample intake passage A3 is connected with the magnetic valve V6 that controls its switch, sample output passage B1 is connected with the magnetic valve V5 that controls its switch, between sample intake passage and sample output passage, be also provided with the connection magnetic valve V7 that controls two channel connections, its open and-shut mode determines that the contact of component mixes, it together determines the mixing ratio of component with the dead volume of the original papers such as micro-magnetic valve, piezoelectric pump on the chip of coupling, in described chip channel, be also provided with minitype piezoelectric pump E1 and sample output passage B2, described sample output passage B2 controls it by outlet magnetic valve V4 and closes.E1 is miniature piezoelectric pump element, and the inverse piezoelectric effect by piezoelectric ceramics makes piezoelectric vibrator produce deformation energy to drive inner fluid passage to flow.
As described in Example 1, between liquid storage channel C 1, C2, be provided with the first sample intake passage A1 and the second sample intake passage A2, the first sample intake passage and the second sample intake passage are respectively equipped with the first magnetic valve V1 and the second magnetic valve V2, be connected with and control the connection magnetic valve V3 that two sample intake passages are communicated with between described V1 and V2.
Can with miniature check valve, partly replace as required in actual applications; Described minitype piezoelectric pump also can be replaced by miniature peristaltic pump.
The circulation that the present embodiment completes three components according to the following steps mixes:
(1) open with magnetic valve V1, V3, the V5 of micro-fluidic chip coupling, V2, V4, V6, V7 close, and E1 closes, and from A1 sample introduction component 1, will be full of C1C2 and flow out from B1 outlet;
(2) V1V3V4V6V7 closes, and V2 V5 opens, and E1 closes, and from A2 sample introduction component 2, will be full of C2 and flow out from B1 outlet;
(3) V1V2V3 closes, and V4V5V6V7 opens, and E1 closes, and from A3 sample introduction component 3, will be full of C3 and export outflow from B1, B2;
(4) V1V2V4V5V6 closes, and V3V7 opens, and E1 opens, and chip internal will form the ring structure of sealing, and under the driving of E1, component 1,2,3 is mixed.
More multi-component mixing is equally by this similar flow operations, and this kind of mixed mode can be avoided being coupled in the dead volume of components and parts and retain the impact of solution on reaction system.
The impact that original paper causes if be coupled in application system is little, and applying step can be reduced to: (1) V1V2V4 V5 opens, and V3V6V7 closes, and E1 closes, and A1, A2 simultaneously sample introduction also flow out from B1B2 outlet respectively; (2) V1V2 V3 closes, and V4V5V6V7 opens, and E1 closes, and A3 sample introduction also flows out from B1B2 outlet; (3) V1V2V4V5V6 closes, and V3V7 opens, and E1 opens, and chip internal will form the ring structure of sealing, and under the driving of E1, component 1,2,3 is mixed.Chip need to clean with distilled water before enabling, and guarantees in passage, there is no obvious bubble (will the affecting the operating efficiency of piezoelectric pump of bubble).
Embodiment 3
Be the micro-fluidic chip by more than two circulation mixed cells form as shown in Figure 3, the present embodiment is to utilize structure shown in Fig. 3 to carry out the pattern that multi-step multicomponent circulation mixes.
As shown in Figure 3, described micro-fluidic chip comprises multi-stage circulating mixed cell, and the exit passageway of previous stage circulation mixed cell is connected successively with the sample intake passage of the circulation mixed cell of rear one-level.Multi-stage circulating mixed cell as shown in Figure 1.
In figure, in previous stage circulation mixed cell, V1, V2 are import magnetic valve, and A1 and A2 are sample intake passage, and V3 is for being communicated with magnetic valve, and C1, C2 are liquid storage passage, and B1 is sample output passage, and E1 is minitype piezoelectric pump.
In rear primary circulation mixed cell, V4, V5 are import magnetic valve, and A3 and A4 are sample intake passage, and V6 is for being communicated with magnetic valve, and C3, C4 are liquid storage passage, and B2 is sample output passage, and E2 is minitype piezoelectric pump.The sample output passage B1 of previous stage circulation mixed cell is communicated with the sample intake passage A4 of rear primary circulation mixed cell.Can with miniature check valve, partly replace as required in actual applications; The open and-shut mode that is communicated with magnetic valve V3, V6 determines that the contact of component mixes; Liquid storage channel C 1, C2, C3, C4 together determine the mixing ratio of component with the dead volume of the original papers such as micro-magnetic valve, piezoelectric pump on the chip of coupling; Minitype piezoelectric pump E1, E2 make piezoelectric vibrator generation deformation energy drive inner fluid passage to flow by the inverse piezoelectric effect of piezoelectric ceramics.
In actual applications, the circulation that completes according to the following steps two components is mixed:
(1) press two component mixed mode flow processs shown in embodiment 1 component 1,2 is fully mixed, B1, B2 open, and other not associated elements are closed;
(2) V1, V2, V3, V4 close, and V5, V6, V7 open, and E1, E2 close, and A4 sample introduction component 3 will be full of C3, C4 and flow out from B2 outlet;
(3) V2, V3, V5, V6 close, and V1, V4, V7 open, and E1, E2 close, and V1 passes into buffering or distilled water is released component 1,2 biased sample from A2 & B1 and entered C3 and flow out from B2 outlet;
(4) V1, V2, V3, V4, V5, V7 close, and V6 opens, and E1 closes, and E2 opens, and chip internal C3, C4 region will form the ring structure of sealing, and under the driving of E1, component 1,2,3 mixed.
More the mixing of multi-step is equally by this similar flow operations, and this kind of mixed mode can be avoided being coupled in the dead volume of components and parts and retain the impact of solution on reaction system.Chip need to clean with distilled water before enabling, and guarantees in passage, there is no obvious bubble (will the affecting the operating efficiency of piezoelectric pump of bubble).
Above embodiment is only in order to technical scheme of the present invention to be described, but not is limited; Although the present invention is had been described in detail with reference to previous embodiment, for the person of ordinary skill of the art, the technical scheme that still can record previous embodiment is modified, or part technical characterictic is wherein equal to replacement; And these modifications or replacement do not make the essence of appropriate technical solution depart from the spirit and scope of the present invention's technical scheme required for protection.
Claims (6)
1. a micro-fluidic chip with circulation mixed structure, it is characterized in that described micro-fluidic chip is provided with circulation mixed cell, described circulation mixed cell comprises chip channel and is located at the first electric hybrid module in chip channel, described the first electric hybrid module comprises two liquid storage passages, two sample intake passages, import magnetic valve and connection magnetic valve, described two sample intake passages are located between two liquid storage passages, on described two sample intake passages, be connected with respectively two import magnetic valves controlling its switch, between two sample intake passages, be also provided with and control the connection magnetic valve that two sample intake passages are communicated with, in described chip channel, be also provided with minitype piezoelectric pump and sample output passage, by outlet solenoid control, it closes described sample output passage.
2. the micro-fluidic chip with circulation mixed structure according to claim 1, it is characterized in that: described micro-fluidic chip comprises multi-stage circulating mixed cell, the exit passageway of previous stage circulation mixed cell is connected successively with the sample intake passage of the circulation mixed cell of rear one-level.
3. a micro-fluidic chip with circulation mixed structure, is characterized in that: described micro-fluidic chip is provided with chip channel, and described chip channel is provided with successively the first electric hybrid module and at least one second electric hybrid module described in the claim 1 connecting;
Described the second electric hybrid module comprises the liquid storage passage being located in chip channel, a sample intake passage, sample output passage and be communicated with magnetic valve, the sample intake passage of described the second electric hybrid module and sample output passage are between the liquid storage passage of the first electric hybrid module and the liquid storage passage of the second electric hybrid module, sample intake passage and sample output passage are also connected with respectively the magnetic valve of controlling its switch, between sample intake passage and sample output passage, be also provided with the connection magnetic valve of controlling two channel connections, in described chip channel, be also provided with minitype piezoelectric pump and sample output passage, by outlet solenoid control, it closes described sample output passage.
4. the micro-fluidic chip with circulation mixed structure according to claim 3, is characterized in that: described magnetic valve and piezoelectric pump are and are coupled on micro-fluidic chip.
5. utilize the circulation mixed method of the micro-fluidic chip with circulation mixed structure described in claim 3, it is characterized in that it comprises the following steps: the magnetic valve of controlling the first component sample introduction is opened, after the first component sample introduction completes, controlling the magnetic valve of second component sample introduction opens, second component sample introduction mixes with the first component, the various components of sample introduction are until all components sample introduction completes successively in order, and various components mixing are reacted.
6. utilize the circulation mixed method of the micro-fluidic chip with circulation mixed structure described in claim 2, it is characterized in that it comprises the following steps: the magnetic valve of controlling the first component sample introduction is opened, after the first component sample introduction completes, controlling the magnetic valve of second component sample introduction opens, after second component sample introduction and the first component hybrid reaction complete, the product of the first component and the second component is mixed and is reacted with the 3rd component, and so sample introduction is until all components sample introduction having reacted.
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| CN104122217A (en) * | 2014-07-29 | 2014-10-29 | 山东省科学院海洋仪器仪表研究所 | Microfluidic-circulation analysis-based high-precision in-situ seawater pH analysis system and method |
| CN108286076A (en) * | 2018-04-17 | 2018-07-17 | 中南大学 | System and its application process is prepared in situ in a kind of biochip |
| WO2020098206A1 (en) * | 2018-11-16 | 2020-05-22 | 南京肯辛顿诊断科技有限公司 | Microfluidic system suitable for liquid mixing, and method |
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