CN103586094B - 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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- CN103586094B CN103586094B CN201310650243.5A CN201310650243A CN103586094B CN 103586094 B CN103586094 B CN 103586094B CN 201310650243 A CN201310650243 A CN 201310650243A CN 103586094 B CN103586094 B CN 103586094B
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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, specifically 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 by constructing organic network with microchannel on the chip of small size, thus 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 advantage such as low cost and high integration, receive the extensive concern of domestic and international researcher expert, and in pollutant monitoring, life science, the fields such as medical treatment & health illustrate good application prospect, facilitate analytical instrument to portable, miniature, integrated development simultaneously.
The controllable operating of microfluid is that microfluidic chip technology realizes the applicable core of its merit, but due to the restriction of micro-technology of preparing, fastens the micro-valve body system of integrated Micropump be also in conceptual phase at chip body, and cannot using widely.The ratio mixing realizing at present solution on chip is general adopts the real-time mixed mode of mechanical type syringe pump, need multiple micro-sampling pump with the use of, adaptability is lacked for reaction system that is long-time, multi-step.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 bringing possibility for the practical application of micro-fluidic chip, the miniaturization for analytical instrument is microminiaturized provides new research direction.But due to the stability of external Small electronic component and the impact of system receipts external environment, the mixing of microfluid in chip channel cannot by the direct control simple realization of extraneous electronic devices and components.Needing the channel system that reasonably matched with external little, micropump valve body system by design and suitable flow passage structure, is solve microchip fluid to control, promotion 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 first electric hybrid module comprises two liquid storage passages, two sample intake passages, import magnetic valve be communicated with magnetic valve, described two sample intake passages are located between two liquid storage passages, described two sample intake passages are connected to two the import magnetic valves controlling its switch, the connection magnetic valve that control two sample intake passage is communicated with also is provided with between two sample intake passages, described chip channel is also provided with minitype piezoelectric pump and sample output passage, described sample output passage controls it by outlet solenoid valve and closes.
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 stage.
Present invention also offers the micro-fluidic chip that another kind has circulation mixed structure, 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 a claim 1 connecting successively;
Described second electric hybrid module comprises the liquid storage passage be located in chip channel, a sample intake passage, sample output passage be communicated with magnetic valve, the sample intake passage of described second electric hybrid module and sample output passage are between the liquid storage passage and the liquid storage passage of the second electric hybrid module of the first electric hybrid module, sample intake passage and sample output passage are also connected to the magnetic valve controlling its switch, the connection magnetic valve of control two channel connection is also provided with between sample intake passage and sample output passage, described chip channel is also provided with minitype piezoelectric pump and sample output passage, described sample output passage controls it by outlet solenoid valve and closes.
Described magnetic valve and piezoelectric pump are and are coupled on micro-fluidic chip.
The described circulation mixed method with the micro-fluidic chip of circulation mixed structure, it comprises the following steps: the magnetic valve controlling the first component sample introduction is opened, after first component sample introduction completes, the magnetic valve controlling second component sample introduction is opened, second component sample introduction mixes with the first component, the various component of sample introduction is until all components sample introduction completes successively in order, and various component mixing is reacted.
The described circulation mixed method with the micro-fluidic chip of circulation mixed structure, it comprises the following steps: the magnetic valve controlling the first component sample introduction is opened, after first component sample introduction completes, the magnetic valve controlling second component sample introduction is opened, after second component sample introduction and the first component hybrid reaction complete, the product of the first component and the second component mixes with three components and reacts, and sample introduction like this 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 multiple pre-stored MCA on chip, different pre-stored interchannels utilizes the miniature electromagnetic valve of closed condition spaced apart, after reacting fluid completes storage by preset ratio in chip channel, open the miniature electromagnetic valve of closed condition, aqueous premix is connected to form closed loop and is dynamically mixed as drive force source by passage microchip connection minitype piezoelectric pump or miniature peristaltic pump.Mixed solution can be imported storage organization on follow-up chip structure and carry out multi-step reaction after having mixed.
Two or more reacting fluid is carried out pre-stored by the open and-shut mode of miniature electromagnetic valve control chip microchannel by chip hybrid mode of the present invention on chip, is controlled the mixing ratio of different mixed solution by the length of microchannel on chip and the dead volume of Connection Element.Can 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 sampling step of solution carries out without the need to real-time synchronization, change the operations such as solution more easily reality.After controlling to form loop by miniature electromagnetic valve, mixing is driven as inner drive source using minitype piezoelectric pump or miniature peristaltic pump, add the operability of fluid, avoid current chip and be blended in the shortcoming can only taking static mixing under chip structure efficiently cannot mix situation completely.By the formation of solenoid control multiple circulation around circuit structure with separate and can control multi-step reaction according to concrete reaction needed, be adapted to complex system and react realization on chip.
After reading the specific embodiment of the present invention by reference to the accompanying drawings, the other features and advantages of the invention will become clearly.
Accompanying drawing explanation
Fig. 1 is the microfluidic chip structure schematic diagram of two component solution circulation mixing in the embodiment of the present invention 1.
Fig. 2 is the microfluidic chip structure schematic diagram of single stage Multi component circulation mixing in the embodiment of the present invention 1.
Fig. 3 is the microfluidic chip structure schematic diagram of multi-step Multi component circulation mixing in the embodiment of the present invention 1.
In figure: A1-A4 is the sample intake passage of different solutions; B1-B2 is solution sample output passage; C1-C4 is liquid storage passage on chip; V1-V7 is the miniature electromagnetic valve that chip is coupled; E1-E2 is the minitype piezoelectric pump that chip is coupled.
Detailed description of the invention
Below in conjunction with the drawings and specific embodiments, technical scheme of the present invention is described in further detail.
Embodiment 1
Micro-fluidic chip as shown in Figure 1 for being made up of single circulation mixed cell, the pattern of the present embodiment for utilizing structure shown in Fig. 1 to carry out two component solution circulation mixing.
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 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 the dead volume of the same element such as magnetic valve, piezoelectric pump be coupled on chip of the liquid storage passage on chip together determines the mixing ratio of component.(A1 is the first sample intake passage to described two sample intake passages, A2 is the second sample intake passage) on be connected to and control two import magnetic valves of its switch, V1 is the first magnetic valve of control first sample intake passage folding and closedown, V2 is the second magnetic valve of control second sample intake passage folding and closedown, what be also connected with the folding of control two passage and closedown between described first sample intake passage A1 and the second sample intake passage A2 is communicated with magnet valve V3, and the open and-shut mode of V3 determines the contact mixing of component; Described chip channel is also provided with minitype piezoelectric pump E1 and sample output passage B, described sample output passage controls it by outlet solenoid valve V4 and closes, and minitype piezoelectric pump E1 makes piezoelectric vibrator produce deformation energy by the inverse piezoelectric effect of piezoelectric ceramics and drives inner fluid passage flowing.
Magnetic valve can be replaced as required in actual applications by miniature check valve part;
The present embodiment completes the circulation mixing of two components according to the following steps:
(1) the first magnetic valve V1 be coupled on micro-fluidic chip opens, 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 will be full of C1, C2 and flow out from B outlet by the first sample intake passage A1 sample introduction component 1;
(2) described V1 closes, and described V2 opens, and described V3 closes, and described V4 opens, and described E1 closes, and will be full of C2 and flow out from B outlet by the second sample intake passage A2 sample introduction component 2;
(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 closed, and component 1,2 is mixed under the driving of E1.This kind of mixed mode can be avoided retaining the impact of solution on reaction system in the dead volume of coupling components and parts.
If not quite, applying step can be reduced to: (1) V1 opens in the impact that in application system, coupling element causes, V2 opens, and V3 closes, and V4 opens, and E1 closes, and sample introduction while of A1, A2 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 closed, and component 1,2 is mixed under the driving of E1.Chip needs before enabling with distilled water cleaning, and ensures do not have obvious bubble (will the affecting the operating efficiency of piezoelectric pump of bubble) in passage.
Embodiment 2
Be by plural circulation mixed cell micro-fluidic chip in series as shown in Figure 2, the pattern of the present embodiment for utilizing structure shown in Fig. 2 to carry out the mixing of single stage Multi component circulation.
As shown in Figure 2, described micro-fluidic chip is provided with chip channel T, and described chip channel is provided with the first electric hybrid module and at least one second electric hybrid module described in an embodiment 1 connecting successively.
Described second electric hybrid module comprises the liquid storage channel C 3 be located in chip channel, a sample intake passage A3, sample output passage B1 be communicated with magnetic valve V7, the sample intake passage A3 of described second electric hybrid module and sample output passage B1 is between the liquid storage channel C 2 and the liquid storage channel C 3 of the second electric hybrid module of the first electric hybrid module, sample intake passage A3 is connected with the magnetic valve V6 controlling its switch, sample output passage B1 is connected with the magnetic valve V5 controlling its switch, the connection magnetic valve V7 of control two channel connection is also provided with between sample intake passage and sample output passage, its open and-shut mode determines the contact mixing of component, its together determines the mixing ratio of component with the dead volume of the original paper such as micro-magnetic valve, piezoelectric pump on chip of coupling, described chip channel is also provided with minitype piezoelectric pump E1 and sample output passage B2, described sample output passage B2 controls it by outlet solenoid valve V4 and closes.E1 is miniature piezoelectric pump element, makes piezoelectric vibrator produce deformation energy drive inner fluid passage flowing by the inverse piezoelectric effect of piezoelectric ceramics.
As described in Example 1, the first sample intake passage A1 and the second sample intake passage A2 is provided with between liquid storage channel C 1, C2, 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, are connected with the connection magnetic valve V3 that control two sample intake passages are communicated with between described V1 and V2.
Can replace by miniature check valve part as required in actual applications; Described minitype piezoelectric pump also can be replaced by miniature peristaltic pump.
The present embodiment completes the circulation mixing of three components according to the following steps:
(1) magnetic valve V1, V3, V5 of being coupled with micro-fluidic chip open, and V2, V4, V6, V7 close, and E1 closes, and will be full of C1C2 and flow out from B1 outlet from A1 sample introduction component 1;
(2) V1V3V4V6V7 closes, and V2 V5 opens, and E1 closes, and will be full of C2 and flow out from B1 outlet from A2 sample introduction component 2;
(3) V1V2V3 closes, and V4V5V6V7 opens, and E1 closes, and will be full of C3 and flow out from B1, B2 outlet from A3 sample introduction component 3;
(4) V1V2V4V5V6 closes, and V3V7 opens, and E1 opens, and chip internal will form the ring structure closed, and component 1,2,3 is mixed under the driving of E1.
More multi-component mixing is equally by this similar flow operations, and this kind of mixed mode can be avoided retaining the impact of solution on reaction system in the dead volume of coupling components and parts.
If the impact that in application system, coupling element causes is little, 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 closed, and component 1,2,3 is mixed under the driving of E1.Chip needs before enabling with distilled water cleaning, and ensures do not have obvious bubble (will the affecting the operating efficiency of piezoelectric pump of bubble) in passage.
Embodiment 3
Micro-fluidic chip as shown in Figure 3 for being made up of two or more circulation mixed cell, the pattern of the present embodiment for utilizing structure shown in Fig. 3 to carry out the mixing of multi-step multicomponent circulation.
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 stage.Multi-stage circulating mixed cell as shown in Figure 1.
In figure, in previous stage circulation mixed cell, V1, V2 are import magnetic valve, A1 and A2 is 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 stage circulation mixed cell, V4, V5 are import magnetic valve, A3 and A4 is 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 stage circulation mixed cell.Can replace by miniature check valve part as required in actual applications; The open and-shut mode being communicated with magnetic valve V3, V6 determines the contact mixing of component; Liquid storage channel C 1, C2, C3, C4 together determine the mixing ratio of component with the dead volume of the original paper such as micro-magnetic valve, piezoelectric pump on the chip of coupling; Minitype piezoelectric pump E1, E2 make piezoelectric vibrator produce deformation energy by the inverse piezoelectric effect of piezoelectric ceramics and drive inner fluid passage flowing.
In actual applications, the circulation mixing of two components will be completed according to the following steps:
(1) by component mixed mode flow process two shown in embodiment 1 by component 1,2 fully mix, and 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, V1, V4, V7 open, E1, E2 close, V1 pass into buffering or distilled water by component 1,2 biased samples release from A2 & B1 enter C3 and from B2 outlet flow out;
(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 closed, and component 1,2,3 is mixed under the driving of E1.
More the mixing of multi-step is equally by this similar flow operations, and this kind of mixed mode can be avoided retaining the impact of solution on reaction system in the dead volume of coupling components and parts.Chip needs before enabling with distilled water cleaning, and ensures do not have obvious bubble (will the affecting the operating efficiency of piezoelectric pump of bubble) in passage.
Above embodiment only in order to technical scheme of the present invention to be described, but not is limited; Although with reference to previous embodiment to invention has been detailed description, for the person of ordinary skill of the art, still can modify to the technical scheme described in previous embodiment, or equivalent replacement is carried out to wherein portion of techniques feature; And these amendments 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. one kind has the micro-fluidic chip of 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 first electric hybrid module comprises two liquid storage passages, two sample intake passages, import magnetic valve be communicated with magnetic valve, described two sample intake passages are located between two liquid storage passages, described two sample intake passages are connected to two the import magnetic valves controlling its switch, the connection magnetic valve that control two sample intake passage is communicated with also is provided with between two sample intake passages, described chip channel is also provided with minitype piezoelectric pump and sample output passage, described sample output passage controls it by outlet solenoid valve and closes.
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 stage.
3. one kind has the micro-fluidic chip of circulation mixed structure, it is characterized in that: described micro-fluidic chip is provided with chip channel, described chip channel is provided with the first electric hybrid module and at least one second electric hybrid module of micro-fluidic chip described in a claim 1 connecting successively;
Described second electric hybrid module comprises the liquid storage passage be located in chip channel, a sample intake passage, sample output passage be communicated with magnetic valve, the sample intake passage of described second electric hybrid module and sample output passage are between the liquid storage passage and the liquid storage passage of the second electric hybrid module of the first electric hybrid module, the sample intake passage of the second electric hybrid module and sample output passage are also connected to the magnetic valve controlling its switch, the connection magnetic valve of control two channel connection is also provided with between the sample intake passage of the second electric hybrid module and sample output passage, described chip channel is also provided with minitype piezoelectric pump and sample output passage, described sample output passage controls it by outlet solenoid valve and closes.
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 with the micro-fluidic chip of circulation mixed structure described in claim 3, it is characterized in that it comprises the following steps: the magnetic valve controlling the first component sample introduction is opened, after first component sample introduction completes, the magnetic valve controlling second component sample introduction is opened, second component sample introduction mixes with the first component, the various component of sample introduction is until all components sample introduction completes successively in order, and various component mixing is reacted.
6. utilize the circulation mixed method with the micro-fluidic chip of circulation mixed structure described in claim 2, it is characterized in that it comprises the following steps: the magnetic valve controlling the first component sample introduction is opened, after first component sample introduction completes, the magnetic valve controlling second component sample introduction is opened, after second component sample introduction and the first component hybrid reaction complete, the product of the first component and the second component mixes with three components and reacts, and sample introduction like this is until all components sample introduction having reacted.
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| CN104122217B (en) * | 2014-07-29 | 2016-09-14 | 山东省科学院海洋仪器仪表研究所 | High accuracy in-situ sea water pH based on micro-fluidic-CIRCULATION ANALYSIS analyzes system and the method for analysis |
| 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 |
| CN109490058B (en) * | 2018-11-16 | 2021-04-20 | 南京爱思唯志生物科技有限公司 | Microfluidic system and method suitable for liquid mixing |
Citations (4)
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| CN1378485A (en) * | 1999-08-12 | 2002-11-06 | Ut-巴特勒有限公司 | Microfluidic device for controlled mianipulation of small volumes |
| CN102000518A (en) * | 2010-09-27 | 2011-04-06 | 华北电力大学 | Micro mixing system of pulsating flow driven by micro bubble pump loop |
| CN102553665A (en) * | 2011-11-04 | 2012-07-11 | 浙江大学 | Microfluidic concentration gradient droplet generating chip, generating device and application |
| CN103055976A (en) * | 2012-12-31 | 2013-04-24 | 苏州汶颢芯片科技有限公司 | Microfluidic chip with oil-water demulsification and separation under electric field/interface synergistic effect and preparation method thereof |
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| EP1618955B1 (en) * | 2004-07-19 | 2010-12-22 | STMicroelectronics Srl | Biological molecules detection device having increased detection rate, and method for quick detection of biological molecules |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1378485A (en) * | 1999-08-12 | 2002-11-06 | Ut-巴特勒有限公司 | Microfluidic device for controlled mianipulation of small volumes |
| CN102000518A (en) * | 2010-09-27 | 2011-04-06 | 华北电力大学 | Micro mixing system of pulsating flow driven by micro bubble pump loop |
| CN102553665A (en) * | 2011-11-04 | 2012-07-11 | 浙江大学 | Microfluidic concentration gradient droplet generating chip, generating device and application |
| CN103055976A (en) * | 2012-12-31 | 2013-04-24 | 苏州汶颢芯片科技有限公司 | Microfluidic chip with oil-water demulsification and separation under electric field/interface synergistic effect and preparation method thereof |
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