CN118950112A - A multi-channel controllable sequential reaction microfluidic chip with integrated elastic valves - Google Patents
A multi-channel controllable sequential reaction microfluidic chip with integrated elastic valves Download PDFInfo
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Abstract
本发明属于微流控检测技术领域，具体涉及一种集成弹性阀的多路可控顺序反应微流控芯片，包括基底层、液体通道层和气体通道层；液体通道层的下表面开设有多个反应腔室，相邻两个反应腔室之间通过液体通道连通；靠近液体通道层一端的反应腔室设有清洗液灌注口；靠近液体通道层另一端的反应腔室设有废液排出口；每个反应腔室均开设有对应的加样口，加样口通过液体通道与反应腔室连通；加样口、清洗液灌注口、废液排出口均贯穿气体通道层与大气连通；气体通道层的下表面开设有与液体通道层液体通道相适配的气体通道，气体通道在液体通道层的垂直投影和与所述气体通道相适配的液体通道相交，形成弹性阀；气体通道层一端封闭，气体通道的另一端设有气体灌注口，气体灌注口与气源连通。本发明微流控芯片通过弹性阀能控制液体进入反应腔室的顺序和速率，能够按照设定的反应顺序，从而实现多路反应的顺序可控。
The present invention belongs to the field of microfluidic detection technology, and specifically relates to a multi-channel controllable sequential reaction microfluidic chip with integrated elastic valves, comprising a substrate layer, a liquid channel layer and a gas channel layer; a plurality of reaction chambers are provided on the lower surface of the liquid channel layer, and two adjacent reaction chambers are connected through a liquid channel; a reaction chamber close to one end of the liquid channel layer is provided with a cleaning liquid injection port; a reaction chamber close to the other end of the liquid channel layer is provided with a waste liquid discharge port; each reaction chamber is provided with a corresponding sample injection port, which is connected to the reaction chamber through a liquid channel; the sample injection port, the cleaning liquid injection port and the waste liquid discharge port all penetrate the gas channel layer and are connected to the atmosphere; a gas channel adapted to the liquid channel of the liquid channel layer is provided on the lower surface of the gas channel layer, and the vertical projection of the gas channel on the liquid channel layer intersects with the liquid channel adapted to the gas channel to form an elastic valve; one end of the gas channel layer is closed, and a gas injection port is provided at the other end of the gas channel, and the gas injection port is connected to a gas source. The microfluidic chip of the present invention can control the order and rate of liquid entering the reaction chamber through the elastic valve, and can realize the controllable order of multi-channel reactions according to the set reaction sequence.
Description
Technical Field
The invention belongs to the technical field of microfluidic detection, and particularly relates to a multichannel controllable sequential reaction microfluidic chip integrated with an elastic valve.
Background
With the rapid development of micro-nano processing technology, different microsystems have great development potential in scientific research and industry, and miniaturization and integration are an important trend of the current development of microsystems. Precise manipulation and control of microfluidics at the micro-nano scale in microsystems remains a major challenge. The micro-fluidic chip can realize rapid mixing and reaction operation of micro-fluid in micro-channel or cavity of micro-to nano-level by micro-nano processing technology, and can integrate micro-valve, micro-pump and micro-electrode in the micro-fluidic chip to realize high precision control of micro-fluid, and the whole micro-system has high integration level and automation. Therefore, the microfluidic chip exhibits its unique advantages in the fields of analytical chemistry, biosynthesis, tissue engineering, drug development, and the like.
The micro valve is one of important elements for realizing micro fluid control in a micro-fluidic chip, and various micro valves are proposed by researchers to comprise a pneumatic micro valve, a piezoelectric micro valve, a magnetic control micro valve and the like, wherein the valve pneumatic micro valve is the most widely applied valve technology at present due to the advantages of simple structure and easiness in integration. The queue pneumatic micro valve is a normally open valve formed by two mutually perpendicular micro fluid channels, wherein one channel is filled with gas, and the other channel is filled with liquid. The channel is deformed by increasing the gas pressure and forcing the liquid channel to deform and eventually shut off the liquid flow. In the microfluidic system, multi-step reaction is carried out without separating fluid injection, and common fluid injection modes can be divided into pipette injection and microinjection pump injection. For the injection of the pipette, the injection efficiency is low, and the injection of the microinjection pump often needs to be provided with an injection pump at an injection port, which clearly greatly increases the cost. The reaction of substances often involves the problem of sequential reaction, and the manual operation of the start and stop of the syringe pump to control the reaction sequence is also a cumbersome process.
Disclosure of Invention
Aiming at the problems and the defects existing in the prior art, the invention aims to provide a multichannel controllable sequential reaction micro-fluidic chip integrated with an elastic valve.
Based on the above purpose, the invention is realized by the following technical scheme:
the invention provides a multichannel controllable sequential reaction micro-fluidic chip integrated with an elastic valve, which comprises a basal layer, wherein a liquid channel layer is connected onto the basal layer in a sealing way, and a gas channel layer is connected onto the liquid channel layer in a sealing way; the lower surface of the liquid channel layer is provided with a plurality of reaction chambers which are sequentially arranged along the length direction of the liquid channel layer, and two adjacent reaction chambers are communicated through a liquid channel; a cleaning liquid filling port is arranged in one reaction chamber near one end of the liquid channel layer, and the cleaning liquid filling port is communicated with the reaction chamber through a liquid channel; a waste liquid outlet is arranged in one reaction chamber close to the other end of the liquid channel layer, and the waste liquid outlet is communicated with the reaction chamber through a liquid channel; each reaction chamber is provided with a corresponding sample adding port, and the sample adding ports are communicated with the reaction chambers through liquid channels; the sample adding port, the cleaning liquid filling port and the waste liquid discharging port are communicated with the atmosphere by penetrating through the gas channel layer; the lower surface of the gas channel layer is provided with gas channels matched with the liquid channels of the liquid channel layer, and the number of the gas channels is the same as that of the liquid channels; the vertical projection of the gas channel on the liquid channel layer is intersected with a liquid channel matched with the gas channel to form an elastic valve; one end of the gas channel layer is closed, and the other end of the gas channel is provided with a gas filling port which is communicated with a gas source.
According to the multi-channel controllable sequential reaction micro-fluidic chip of the integrated elastic valve, preferably, the gas channel layer and the liquid channel layer are both made of flexible materials; more preferably, the gas channel layer and the liquid channel layer are both cast by PDMS (polydimethylsiloxane) material or COC plastic. The specific preparation methods of the gas channel layer and the liquid channel layer are as follows: firstly, preparing a male die of the gas channel layer and the liquid channel layer by a soft lithography technology, then pouring PDMS material or COC plastic on the surface of the male die, and drying to obtain the gas channel layer and the liquid channel layer respectively.
According to the multi-channel controllable sequential reaction micro-fluidic chip of the integrated elastic valve, preferably, the substrate layer is made of transparent materials. More preferably, the substrate layer is made of transparent glass or PMMA polymer.
According to the multi-channel controllable sequential reaction micro-fluidic chip of the integrated elastic valve, preferably, the thickness of the gas channel layer is 3-6 mm, and the thickness of the liquid channel layer is 30-100 μm.
According to the multi-channel controllable sequential reaction micro-fluidic chip of the integrated elastic valve, preferably, an included angle formed by the perpendicular projection of the gas channel on the liquid channel layer and the intersection of the gas channel and the liquid channel matched with the gas channel is 90 degrees.
According to the multi-channel controllable sequential reaction micro-fluidic chip of the integrated elastic valve, preferably, the sample adding port is communicated with a sample storage pool, and the sample storage pool is communicated with an air source; the number of the sample adding ports corresponding to each reaction chamber is set according to the type of the sample adding substances required.
According to the multi-channel controllable sequential reaction micro-fluidic chip of the integrated elastic valve, preferably, the number of the reaction chambers is set according to the requirement of the product to be detected.
According to the multi-channel controllable sequential reaction micro-fluidic chip of the integrated elastic valve, preferably, the liquid channel between the waste liquid outlet and the reaction chamber is a serpentine liquid channel, and the vertical projection of the gas channel matched with the serpentine liquid channel on the liquid channel layer is positioned at the communication position between the serpentine liquid channel and the reaction chamber.
According to the multi-channel controllable sequential reaction micro-fluidic chip of the integrated elastic valve, preferably, two reaction chambers are provided, a first reaction chamber is provided with a first sample adding port, and the first sample adding port is communicated with the first reaction chamber through a first liquid channel; the second reaction chamber is provided with a second sample adding port and a third sample adding port, and the second sample adding port and the third sample adding port are communicated with the second reaction chamber through a second liquid channel and a third liquid channel respectively; the two reaction chambers are communicated through a fourth liquid channel; the first reaction chamber is communicated with the cleaning liquid filling port through a sixth liquid channel, and the second reaction chamber is communicated with the waste liquid outlet through a fifth liquid channel; the first elastic valve is formed by the first liquid channel and the gas channel corresponding to the gas channel layer, the second elastic valve is formed by the second liquid channel and the gas channel corresponding to the gas channel layer, the third elastic valve is formed by the third liquid channel and the gas channel corresponding to the gas channel layer, the fourth elastic valve is formed by the fourth liquid channel and the gas channel corresponding to the gas channel layer, the fifth elastic valve is formed by the fifth liquid channel and the gas channel corresponding to the gas channel layer, and the sixth elastic valve is formed by the sixth liquid channel and the gas channel corresponding to the gas channel layer.
According to the multi-channel controllable sequential reaction micro-fluidic chip of the integrated elastic valve, preferably, the substrate layer, the liquid channel layer and the gas channel layer are all in sealing connection in a plasma bonding mode.
According to the multi-channel controllable sequential reaction micro-fluidic chip integrated with the elastic valve, preferably, a plurality of cleaning liquid filling openings are formed, and the liquid channel layer and the gas channel layer are provided with alignment marks.
The second aspect of the present invention provides a method for detecting whether escherichia coli is contained in water by using the integrated elastic valve multi-channel controllable sequential reaction micro-fluidic chip of the first aspect, comprising the following steps:
(1) Introducing gas into the gas channels of the gas channel layer corresponding to the second liquid channel, the third liquid channel and the sixth liquid channel to enable the second elastic valve, the third elastic valve and the sixth elastic valve to be in a working state, adding a water sample to be detected into the first reaction chamber from the first sample adding port, and then introducing gas into the gas channels of the gas channel layer corresponding to the fourth liquid channel and the fifth liquid channel to enable the fourth elastic valve and the fifth elastic valve to be in a working state;
(2) Adding a protein extraction reagent into the first reaction chamber from the first sample adding port, and after the first reaction chamber is full of liquid, introducing gas into a gas channel corresponding to the first liquid channel of the gas channel layer to enable the first elastic valve to be in a working state; after the reaction of the water sample to be detected and the protein extraction reagent is finished, stopping introducing gas into the gas channel corresponding to the gas channel layer and the fourth liquid channel to enable the fourth elastic valve to be in a stop working state, enabling the liquid in the first reaction chamber to enter the second reaction chamber through the fourth liquid channel, and then introducing gas into the gas channel corresponding to the gas channel layer and the fourth liquid channel to enable the fourth elastic valve to be in a working state;
(3) Stopping introducing gas into the gas channel corresponding to the second liquid channel of the gas channel layer to enable the second elastic valve to be in a stop working state, adding a polyvinyl amine solution into the second reaction chamber from the second sample adding port, and then introducing gas into the gas channel corresponding to the second liquid channel of the gas channel layer to enable the second elastic valve to be in a working state;
(4) Stopping introducing gas into the gas channel corresponding to the third liquid channel of the gas channel layer to enable the third elastic valve to be in a stop working state, adding chlorophenol red-beta-D-galactopyranoside solution into the second reaction chamber from the third sample adding port, and then introducing gas into the gas channel corresponding to the second liquid channel of the gas channel layer to enable the second elastic valve to be in a working state; after the reaction of the chlorophenol red-beta-D-galactopyranoside solution and the liquid in the second reaction chamber is finished, judging whether the water sample to be detected contains escherichia coli according to the color of the liquid in the second reaction chamber; if the color of the liquid in the second reaction chamber is blue, the water sample to be detected contains escherichia coli, and if the color of the liquid in the second reaction chamber is colorless, the water sample to be detected does not contain escherichia coli;
(5) After the test is finished, stopping introducing gas into the gas channels of the gas channel layer corresponding to the fourth liquid channel, the fifth liquid channel and the sixth liquid channel, enabling the fourth elastic valve, the fifth elastic valve and the sixth elastic valve to be in a stop working state, then injecting cleaning liquid into the cleaning liquid filling port, and discharging liquid in the first reaction chamber, the second reaction chamber and the liquid channel from the waste liquid discharge port.
Compared with the prior art, the invention has the following positive and beneficial effects:
(1) The gas channel layer is positioned above the liquid channel layer, the lower surface of the gas channel layer is provided with a gas channel matched with the liquid channel of the liquid channel layer, the vertical projection of the gas channel on the liquid channel layer is intersected with the liquid channel matched with the gas channel, the gas channel on the lower surface of the gas channel layer is an open channel, and only after the gas channel layer is sealed and fixed on the liquid channel layer, the gas channel in the gas channel layer is closed; the liquid channel layer and the gas channel layer are made of flexible materials, and after gas is introduced into the gas channel, the liquid channel layer is pressed under the action of gas pressure, so that the liquid channel layer is deformed to form an elastic valve; the elastic valve can generate nonlinear deformation under the action of different pressures, so that the liquid channel is pressed to different degrees, the flow of reactants in the liquid channel is changed or the corresponding liquid channel is cut off, thereby realizing the control of the liquid flow in the liquid channel, the adjustment of the injection quantity of the reactants and the control of the reaction rate in the reaction cavity.
(2) According to the invention, the sample adding port of the reaction chamber is communicated with the reaction storage tank, the reaction storage tank is communicated with the gas source, reactants can be pumped into the microfluidic chip through the gas source pressure, and simultaneous injection into the chip fluid channel can be realized, but the elastic valve is opened according to a set reaction sequence because the elastic valve does not enter the reaction chamber at the same time, so that the reactants enter the reaction chamber, and the sequence of multipath reaction is controllable.
(3) The thickness of the gas channel layer is preferably 3-6 mm, and the thickness of the liquid channel layer is preferably 30-100 mu m, so that the liquid channel corresponding to the gas channel is easy to deform after the gas is introduced into the gas channel, the sensitivity of the elastic valve is greatly improved, and the sensitivity of the microfluidic chip for sequential reaction control is improved.
Drawings
Fig. 1 is a schematic diagram of the overall structure of a multi-channel controllable sequential reaction microfluidic chip integrated with an elastic valve in embodiment 1 of the present invention;
FIG. 2 is an exploded view of a multi-channel controllable sequential reaction microfluidic chip with an integrated elastic valve according to embodiment 1 of the present invention;
FIG. 3 is a schematic diagram of the structure of the gas channel layer of the multi-channel controllable sequential reaction microfluidic chip integrated with the elastic valve in embodiment 1 of the present invention;
Fig. 4 is a schematic structural diagram of a liquid channel layer of a multi-channel controllable sequential reaction microfluidic chip integrated with an elastic valve in embodiment 1 of the present invention;
fig. 5 is a schematic structural diagram of a substrate layer of a multi-channel controllable sequential reaction micro-fluidic chip integrated with an elastic valve in embodiment 1 of the present invention;
FIG. 6 is a schematic diagram of the structure of the lower surface of the liquid channel layer of the multi-channel controllable sequential reaction microfluidic chip integrated with an elastic valve in embodiment 1 of the present invention;
FIG. 7 is a schematic diagram showing the structure of the upper surface of the liquid channel layer of the multi-channel controllable sequential reaction microfluidic chip integrated with an elastic valve in embodiment 1 of the present invention;
FIG. 8 is a schematic diagram of the structure of the lower surface of the gas channel layer of the multi-channel controllable sequential reaction microfluidic chip integrated with an elastic valve in embodiment 1 of the present invention;
FIG. 9 is a schematic diagram showing the structure of the upper surface of the gas channel layer of the multi-channel controllable sequential reaction micro-fluidic chip integrated with the elastic valve in embodiment 1 of the present invention;
fig. 10 is a schematic diagram showing the distribution of the elastic valves (vertical projection of the gas channel on the liquid channel layer) of the multi-channel controllable sequential reaction microfluidic chip integrated with the elastic valves in embodiment 1 of the present invention;
Fig. 11 is a schematic diagram of the working principle of an elastic valve (a cross-sectional view at the elastic valve) of the multi-channel controllable sequential reaction microfluidic chip integrated with the elastic valve in embodiment 1 of the present invention;
Fig. 12 is a physical diagram of a multi-channel controllable sequential reaction micro-fluidic chip integrated with an elastic valve in embodiment 1 of the present invention and an actual working state diagram of the elastic valve.
In the figure, 1 is a gas channel layer, 2 is a liquid channel layer, 3 is a substrate layer, 111 is a sixth gas injection port, 112 is a first gas injection port, 113 is a second gas injection port, 114 is a fifth gas injection port, 115 is a third gas injection port, 116 is a fourth gas injection port, 117 is a seventh gas injection port, 120 is a gas channel, 121 is a sixth gas channel, 122 is a seventh gas channel, 123 is a fourth gas channel, 124 is a third gas channel, 125 is a fifth gas channel, 126 is a second gas channel, 127 is a first gas channel, 131 is a cross alignment mark, 132 is a cross alignment mark, 211 is a first cleaning liquid injection port, 212 is a first sample injection port, 213 is a second sample injection port, 214 is a waste liquid discharge port, 215 is a third sample inlet, 216 is a second cleaning liquid filling port, 220 is a liquid channel, 221 is a sixth liquid channel, 222 is a first liquid channel, 223 is a fourth liquid channel, 224 is a second liquid channel, 225 is a fifth liquid channel, 226 is a third liquid channel, 227 is a seventh liquid channel, 231 is a cross alignment mark, 232 is a cross alignment mark, 241 is a second reaction chamber, 242 is a first reaction chamber, 411 is a sixth elastic valve, 412 is a seventh elastic valve, 413 is a first elastic valve, 414 is a fourth elastic valve, 415 is a second elastic valve, 416 is a third elastic valve, 417 is a fifth elastic valve, 511 indicates that the chip entity is in a stop working state, 512 indicates that the elastic valve is in a working state.
Detailed Description
The present invention will be described in further detail by way of the following specific examples, which are not intended to limit the scope of the present invention. The structures, proportions, sizes, etc. shown in the drawings provided in the embodiments are for illustration purposes only and should not be construed as limiting the invention to those skilled in the art, therefore, without any technical significance, any structural modification, proportional relation change or size adjustment should still fall within the scope covered by the technical disclosure without affecting the efficacy and achievement of the present invention. Also, the terms such as "upper," "lower," "left," "right," "middle," and "a" and the like recited in the present specification are merely for descriptive purposes and are not intended to limit the scope of the invention, but are intended to provide relative positional changes or modifications without materially altering the technical context in which the invention may be practiced.
Example 1:
The multi-channel controllable sequential reaction micro-fluidic chip integrated with the elastic valve is composed of a substrate layer 3, a liquid channel layer 2 and a gas channel layer 1 from bottom to top in sequence as shown in fig. 1-5, wherein the liquid channel layer 2 is hermetically connected to the substrate layer 3 by adopting a plasma bonding technology, and the gas channel layer 1 is hermetically connected to the liquid channel layer 2 by adopting the plasma bonding technology. The gas channel layer 1 and the liquid channel layer 2 are preferably cast from PDMS (polydimethylsiloxane) material or COC plastic, and the base layer 3 is preferably made of transparent glass or PMMA polymer. The thickness of the gas passage layer 1 is preferably 3 to 6mm, and the thickness of the liquid passage layer 2 is preferably 30 to 100 μm.
The lower surface of the liquid channel layer 2 (as shown in fig. 6 and 7) is provided with a first reaction chamber 242 and a second reaction chamber 241, and the first reaction chamber 242 and the second reaction chamber 241 are arranged in this order in the longitudinal direction of the liquid channel layer 2. The first reaction chamber 242 is provided with a first sample addition port 212, a first cleaning liquid filling port 211 and a second cleaning liquid filling port 216, the first sample addition port 212 is communicated with the first reaction chamber 242 through a first liquid channel 222, the first cleaning liquid filling port 211 is communicated with the first reaction chamber 242 through a sixth liquid channel 221, and the second cleaning liquid filling port 216 is communicated with the first reaction chamber 242 through a seventh liquid channel 227. The second reaction chamber 241 is communicated with the first reaction chamber 242 through the fourth liquid channel 223, the second reaction chamber 241 is provided with a second loading port 213, a third loading port 215 and a waste liquid discharge port 214, the second loading port 213 is communicated with the second reaction chamber 241 through the second liquid channel 224, the third loading port 215 is communicated with the second reaction chamber 241 through the third liquid channel 226, and the waste liquid discharge port 214 is communicated with the second reaction chamber 241 through the fifth liquid channel 225, preferably, the fifth liquid channel 225 is a serpentine liquid channel. The first sample addition port 212, the second sample addition port 213, the third sample addition port 215, the first cleaning liquid filling port 211, the second cleaning liquid filling port 216, and the waste liquid discharge port 214 are all communicated with the atmosphere through the gas channel layer 1. Further, the first sample adding port 212, the second sample adding port 213 and the third sample adding port 215 are all communicated with a sample storage pool, the sample storage pool is communicated with an air source, and samples or reagents can be pumped into the microfluidic chip from the sample adding ports through air source pressure. In addition, the liquid channel layer 2 is provided with a cross alignment mark, so that the gas channel layer 1 is conveniently assembled on the liquid channel layer 2 when the chip is prepared.
The lower surface of the gas channel layer 1 is provided with gas channels matched with the liquid channels of the liquid channel layer 2, the number of the gas channels is the same as that of the liquid channels, one end of the gas channel layer 1 is closed, the other end of the gas channel is provided with a gas filling opening, the gas filling opening is communicated with a gas source, and the vertical projection of the gas channel on the liquid channel layer 2 is intersected with the liquid channels matched with the gas channels (preferably, an included angle formed by the intersection is 90 degrees) to form an elastic valve. The specific structure of the gas channel layer 1 (as shown in fig. 8 and 9) is: the lower surface of the gas channel layer 1 is provided with a first gas channel 127, a second gas channel 126, a third gas channel 124, a fourth gas channel 123, a fifth gas channel 125, a sixth gas channel 121 and a seventh gas channel 122 which are respectively matched with the first liquid channel 222, the second liquid channel 224, the third liquid channel 226, the fourth liquid channel 223, the fifth liquid channel 225, the sixth liquid channel 221 and the seventh liquid channel 227; one end of the first gas passage 127, the second gas passage 126, the third gas passage 124, the fourth gas passage 123, the fifth gas passage 125, the sixth gas passage 121, and the seventh gas passage 122 is provided with a first gas filling port 112, a second gas filling port 113, a third gas filling port 115, a fourth gas filling port 116, a fifth gas filling port 114, a sixth gas filling port 111, and a seventh gas filling port 117, respectively. The vertical projection of the first gas channel 127 on the liquid channel layer 2 intersects the first liquid channel 222 to form a first elastic valve 413, the vertical projection of the second gas channel 126 on the liquid channel layer 2 intersects the second liquid channel 224 to form a second elastic valve 415, the vertical projection of the third gas channel 124 on the liquid channel layer 2 intersects the third liquid channel 226 to form a third elastic valve 416, the vertical projection of the fourth gas channel 123 on the liquid channel layer 2 intersects the fourth liquid channel 223 to form a fourth elastic valve 414, the vertical projection of the fifth gas channel 125 on the liquid channel layer 2 intersects the fifth liquid channel 225 to form a fifth elastic valve 417, the vertical projection of the sixth gas channel 121 on the liquid channel layer 2 intersects the sixth liquid channel 221 to form a sixth elastic valve 411, the vertical projection of the seventh gas channel 122 on the liquid channel layer 2 intersects the seventh liquid channel 227 to form a seventh elastic valve 412. In addition, the gas channel layer 1 is provided with the same cross alignment mark as the liquid channel layer 2, so that the gas channel layer 1 is conveniently assembled on the liquid channel layer 2 when the chip is prepared.
Example 2:
a method for detecting whether escherichia coli is contained in water by utilizing the multichannel controllable sequential reaction micro-fluidic chip integrated with the elastic valve in the embodiment 1 comprises the following specific steps:
(1) Introducing gas into the second gas channel 126, the third gas channel 124, the sixth gas channel 121 and the seventh gas channel 122 through the second gas filling port 113, the third gas filling port 115, the sixth gas filling port 111 and the seventh gas filling port 117 respectively, enabling the second elastic valve 415, the third elastic valve 416, the sixth elastic valve 411 and the seventh elastic valve 412 to be in a working state, adding a water sample to be detected into the first reaction chamber 242 from the first sample adding port 212, and introducing gas into the fourth gas channel 123 and the fifth gas channel 125 through the fourth gas filling port 116 and the fifth gas filling port 114 after the water sample to be detected in the first reaction chamber 242 is half, and enabling the fourth elastic valve 414 and the fifth elastic valve 417 to be in a working state;
(2) Protein extraction reagent is added into the first reaction chamber 242 from the first sample adding port 212, and after the first reaction chamber 242 is fully filled with liquid, gas is introduced into the first gas channel 127 through the first gas filling port 112, so that the first elastic valve 413 is in a working state; after the reaction of the water sample to be detected and the protein extraction reagent is completed, stopping introducing gas into the fourth gas channel 123, so that the fourth elastic valve 414 is in a stop working state, enabling the liquid in the first reaction chamber 242 to enter the second reaction chamber 241 through the fourth fluid channel, and then introducing gas into the fourth gas channel 123 through the fourth gas filling port 116, so that the fourth elastic valve 414 is in a working state;
(3) Stopping introducing gas into the second gas channel 126, enabling the second elastic valve 415 to be in a stop working state, adding a polyvinyl amine solution into the second reaction chamber 241 from the second sample adding port 213, and then introducing gas into the second gas channel 126 through the second gas filling port 113, so that the second elastic valve 415 is in a working state;
(4) Stopping the gas from being introduced into the third gas channel 124, so that the third elastic valve 416 is in a stop working state, adding chlorophenol red-beta-D-galactopyranoside solution into the second reaction chamber 241 from the third sample adding port 215, and then introducing gas into the second gas channel 126 through the second gas filling port 113, so that the second elastic valve 415 is in a working state; after the reaction of the chlorophenol red-beta-D-galactopyranoside solution and the liquid in the second reaction chamber 241 is finished, judging whether the water sample to be detected contains escherichia coli according to the color of the liquid in the second reaction chamber 241; if the color of the liquid in the second reaction chamber 241 is blue, it indicates that the water sample to be tested contains escherichia coli, and if the color of the liquid in the second reaction chamber is colorless, it indicates that the water sample to be tested does not contain escherichia coli;
(5) After the test, the fourth, fifth and sixth gas passages 123, 125, 121 are stopped from being supplied with gas, the fourth, fifth and sixth elastic valves 414, 417, 411 are brought into a stopped state, and then the cleaning liquid is injected into the first and second cleaning liquid injection ports 216, respectively, so that the liquid in the first, second and liquid passages 242, 241 is discharged from the waste liquid discharge port 214.
The working principle of the elastic valve of the invention (as shown in fig. 11) is as follows: the lower surface of the gas channel layer is provided with a gas channel matched with the liquid channel of the liquid channel layer, the gas channel is an open channel, and the gas channel in the gas channel layer is closed only after the gas channel layer is sealed and fixed on the liquid channel layer; the liquid channel layer and the gas channel layer are made of flexible materials, and after gas is introduced into the gas channel, the liquid channel layer is pressed under the action of gas pressure, so that the liquid channel layer is deformed to form an elastic valve; the elastic valve can generate nonlinear deformation under the action of different pressures, so that the liquid channel is pressed to different degrees, the flow of reactants in the liquid channel is changed or the corresponding liquid channel is cut off, thereby realizing the control of the flow of the liquid in the liquid channel and the adjustment of the flow rate, and realizing the reaction control in the reaction cavity; when the gas is stopped from being introduced into the gas channel, the gas pressure is eliminated, the liquid channel layer is restored to the original shape, and the elastic valve stops working. Fig. 12 is a physical diagram of a multi-channel controllable sequential reaction micro-fluidic chip integrated with an elastic valve designed by the invention, 512 is a state diagram of stopping operation, and 513 is a working state diagram of the elastic valve in a working state.
Finally, it should be noted that: the above embodiments are merely preferred embodiments of the present invention, and are not intended to limit the present invention in any way, and any person skilled in the art may make modifications or alterations using the above technical matters as a teaching. Equivalent embodiments of this equivalent variation. However, all the simple modifications, equivalent changes and modifications made to the above embodiments according to the technical substance of the present invention, which do not depart from the technical idea of the present invention, still fall within the scope of the appended claims.
Claims (8)
1. The multichannel controllable sequential reaction micro-fluidic chip integrated with the elastic valve is characterized by comprising a basal layer, wherein a liquid channel layer is connected onto the basal layer in a sealing manner, and a gas channel layer is connected onto the liquid channel layer in a sealing manner; the lower surface of the liquid channel layer is provided with a plurality of reaction chambers which are sequentially arranged along the length direction of the liquid channel layer, and two adjacent reaction chambers are communicated through a liquid channel; a cleaning liquid filling port is arranged in one reaction chamber close to one end of the liquid channel layer, the cleaning liquid filling port is communicated with the reaction chamber through a liquid channel, a waste liquid outlet is arranged in one reaction chamber close to the other end of the liquid channel layer, and the waste liquid outlet is communicated with the reaction chamber through the liquid channel; each reaction chamber is provided with a corresponding sample adding port, and the sample adding ports are communicated with the reaction chambers through liquid channels; the sample adding port, the cleaning liquid filling port and the waste liquid discharging port are communicated with the atmosphere by penetrating through the gas channel layer; the lower surface of gas channel layer has seted up the gas channel with liquid channel layer liquid channel looks adaptation, gas channel quantity is the same with liquid channel quantity, gas channel at the perpendicular projection of liquid channel layer with the liquid channel of gas channel looks adaptation intersects, forms the elastic valve, gas channel layer one end is sealed, and gas channel's the other end is equipped with the gas filling mouth, gas filling mouth and air supply intercommunication.
2. The integrated elastic valve multichannel controllable sequential reaction microfluidic chip according to claim 1, wherein the gas channel layer and the liquid channel layer are both made of flexible materials, and the substrate layer is made of transparent materials.
3. The integrated elastic valve multi-channel controllable sequential reaction micro-fluidic chip of claim 2, wherein the thickness of the gas channel layer is 3-6 mm, and the thickness of the liquid channel layer is 30-100 μm.
4. The integrated elastic valve multi-channel controllable sequential reaction micro-fluidic chip according to claim 2, wherein an included angle formed by the vertical projection of the gas channel on the liquid channel layer and the intersection of the gas channel and the liquid channel matched with the gas channel is 90 degrees; the sample adding port is communicated with the sample storage tank, and the reaction liquid storage tank is communicated with the air source; the number of the sample adding ports corresponding to each reaction chamber is set according to the type of the sample adding substances required.
5. The integrated elastic valve multichannel controllable sequential reaction microfluidic chip according to claim 1, wherein the liquid channel between the waste liquid outlet and the reaction chamber is a serpentine liquid channel, and the vertical projection of the gas channel matched with the serpentine liquid channel on the liquid channel layer is located at the communication position between the serpentine liquid channel and the reaction chamber.
6. The integrated elastic valve multi-channel controllable sequential reaction micro-fluidic chip according to any one of claims 1-5, wherein two reaction chambers are provided, a first reaction chamber is provided with a first sample adding port, and the first sample adding port is communicated with the first reaction chamber through a first liquid channel; the second reaction chamber is provided with a second sample adding port and a third sample adding port, and the second sample adding port and the third sample adding port are communicated with the second reaction chamber through a second liquid channel and a third liquid channel respectively; the two reaction chambers are communicated through a fourth liquid channel; the first reaction chamber is communicated with the cleaning liquid filling port through a sixth liquid channel, and the second reaction chamber is communicated with the waste liquid outlet through a fifth liquid channel; the first elastic valve is formed by the first liquid channel and the gas channel corresponding to the gas channel layer, the second elastic valve is formed by the second liquid channel and the gas channel corresponding to the gas channel layer, the third elastic valve is formed by the third liquid channel and the gas channel corresponding to the gas channel layer, the fourth elastic valve is formed by the fourth liquid channel and the gas channel corresponding to the gas channel layer, the fifth elastic valve is formed by the fifth liquid channel and the gas channel corresponding to the gas channel layer, and the sixth elastic valve is formed by the sixth liquid channel and the gas channel corresponding to the gas channel layer.
7. The integrated elastic valve multichannel controllable sequential reaction microfluidic chip according to claim 6, wherein the substrate layer, the liquid channel layer and the gas channel layer are all hermetically connected in a plasma bonding manner; the cleaning liquid filling openings are provided with a plurality of cleaning liquid filling openings, and the liquid channel layer and the gas channel layer are provided with alignment marks.
8. A method for detecting whether escherichia coli is contained in water by using the integrated elastic valve multi-channel controllable sequential reaction micro-fluidic chip as defined in claim 6 or 7, which is characterized by comprising the following steps:
(1) Introducing gas into the gas channels of the gas channel layer corresponding to the second liquid channel, the third liquid channel and the sixth liquid channel to enable the second elastic valve, the third elastic valve and the sixth elastic valve to be in a working state, adding a water sample to be detected into the first reaction chamber from the first sample adding port, and then introducing gas into the gas channels of the gas channel layer corresponding to the fourth liquid channel and the fifth liquid channel to enable the fourth elastic valve and the fifth elastic valve to be in a working state;
(2) Adding a protein extraction reagent into the first reaction chamber from the first sample adding port, and after the first reaction chamber is full of liquid, introducing gas into a gas channel corresponding to the first liquid channel of the gas channel layer to enable the first elastic valve to be in a working state; after the reaction of the water sample to be detected and the protein extraction reagent is finished, stopping introducing gas into the gas channel corresponding to the gas channel layer and the fourth liquid channel to enable the fourth elastic valve to be in a stop working state, enabling the liquid in the first reaction chamber to enter the second reaction chamber through the fourth liquid channel, and then introducing gas into the gas channel corresponding to the gas channel layer and the fourth liquid channel to enable the fourth elastic valve to be in a working state;
(3) Stopping introducing gas into the gas channel corresponding to the second liquid channel of the gas channel layer to enable the second elastic valve to be in a stop working state, adding a polyvinyl amine solution into the second reaction chamber from the second sample adding port, and then introducing gas into the gas channel corresponding to the second liquid channel of the gas channel layer to enable the second elastic valve to be in a working state;
(4) Stopping introducing gas into the gas channel corresponding to the third liquid channel of the gas channel layer to enable the third elastic valve to be in a stop working state, adding chlorophenol red-beta-D-galactopyranoside solution into the second reaction chamber from the third sample adding port, and then introducing gas into the gas channel corresponding to the second liquid channel of the gas channel layer to enable the second elastic valve to be in a working state; after the reaction of the chlorophenol red-beta-D-galactopyranoside solution and the liquid in the second reaction chamber is finished, judging whether the water sample to be detected contains escherichia coli according to the color of the liquid in the second reaction chamber; if the color of the liquid in the second reaction chamber is blue, indicating that the water sample to be detected contains escherichia coli;
(5) After the test is finished, stopping introducing gas into the gas channels of the gas channel layer corresponding to the fourth liquid channel, the fifth liquid channel and the sixth liquid channel, enabling the fourth elastic valve, the fifth elastic valve and the sixth elastic valve to be in a stop working state, then injecting cleaning liquid into the cleaning liquid filling port, and discharging liquid in the first reaction chamber, the second reaction chamber and the liquid channel from the waste liquid discharge port.
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