CN111617812B - Microfluidic substrate, fluid driving method thereof and microfluidic device - Google Patents
Microfluidic substrate, fluid driving method thereof and microfluidic device Download PDFInfo
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- CN111617812B CN111617812B CN201910988391.5A CN201910988391A CN111617812B CN 111617812 B CN111617812 B CN 111617812B CN 201910988391 A CN201910988391 A CN 201910988391A CN 111617812 B CN111617812 B CN 111617812B
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
Abstract
Disclosed are a microfluidic substrate, a fluid driving method thereof, and a microfluidic device. The microfluidic substrate comprises a first quantification having a first volume and configured to provide a first volume of a first fluid equal to the first volume.
Description
Technical Field
The present disclosure relates to the field of biological detection, and more particularly to microfluidic substrates and methods of driving fluids thereof, microfluidic devices.
Background
The microfluidic device is also called a Lab-on-a-chip (Lab-on-a-chip), and is used for integrating basic operation units related to the fields of biology, chemistry, medicine and the like, such as sample preparation, reaction, separation, detection and the like, on a chip with a micro-channel with a micron scale, and automatically completing the whole process of reaction and analysis. The analytical detection device based on the microfluidic device has the advantages that: the sample consumption is less, the analysis speed is fast, the portable instrument is convenient to manufacture, and the method is very suitable for real-time and on-site analysis. To automate and integrate an analysis and detection device based on a microfluidic device, it is necessary to integrate various functions of reaction, analysis, and the like into the device as much as possible while reducing the dependence on operations outside the device. Furthermore, the microfluidic device may be designed as a disposable product, which may eliminate complex fluid path systems such as cleaning and waste fluid treatment.
Disclosure of Invention
In one aspect, embodiments of the present disclosure provide a microfluidic substrate including: a first volume having a first volume and configured to provide a first volume of a first fluid equal to the first volume.
In some embodiments, the microfluidic substrate further comprises a first feed, a second feed and a first drain, wherein the first dosing comprises a first port and a second port, the first dosing being in fluid communication with the first feed through the first port and in fluid communication with the second feed and the first drain through the second port, respectively.
In some embodiments, the first feed is configured to provide a first fluid greater than the first volume to the first volume through the first port, and the second feed is configured to provide a second fluid.
In some embodiments, the microfluidic substrate further comprises a second dosing section for dosing a volume of a mixture of both the first fluid and the second fluid, the second dosing section comprising a membrane pump chamber having a second volume, the membrane pump chamber comprising an elastic membrane and being configured to dose the second volume by controlling an amount of deformation of the elastic membrane.
In some embodiments, the second dosing section comprises a third port and a fourth port, the third port being in fluid communication with the first port.
In some embodiments, the microfluidic substrate further comprises a third quantitative section having a third volume and configured to quantitatively control a volume of the fluid in the third quantitative section.
In some embodiments, the third quantification section comprises a detection site and the third quantification section comprises a fifth port and a sixth port, the fifth port being in fluid communication with the fourth port.
In some embodiments, the microfluidic substrate further comprises a second vent in fluid communication with the sixth port and configured to receive fluid flowing from the third dosing section.
In some embodiments, the microfluidic substrate further comprises a main body part and a first cover part, wherein the main body part and the first cover part are attached to form the first quantitative part, the first feeding part, the second feeding part, the first discharging part, the second quantitative part, the third quantitative part and the second discharging part.
In some embodiments, the first cover comprises a composite structure of a hydrophilic layer and an elastic layer.
In some embodiments, the microfluidic substrate further comprises a second cover on a side of the main body portion away from the first cover, the second cover being for sealing one or more of the first feed portion, the second feed portion, the first drain portion, and the second drain portion.
In another aspect, embodiments of the present disclosure also provide a microfluidic device including the above microfluidic substrate.
In yet another aspect, embodiments of the present disclosure also provide a fluid driving method for a microfluidic substrate, including: driving a first fluid flow through the first port to fill the first metering section, excess first fluid flowing into the first discharge section during filling; wherein the first volume has a first volume and is configured to provide a first volume of a first fluid equal to the first volume.
In some embodiments, the fluid driving method further comprises, after driving the first fluid flow through the first port to fill the first volume: the second fluid is driven to flow through the second port and enter the first quantitative portion, and meanwhile the first fluid in the first quantitative portion flows to the second quantitative portion through the first port.
In some embodiments, the fluid driving method further comprises, after driving the second fluid flow through the second port into the first volume: driving the first fluid and the second fluid into the second dosing section until the mixture of the first fluid and the second fluid reaches a predefined volume in the second dosing section, wherein the second dosing section comprises a membrane pump chamber having a second volume, the membrane pump chamber comprising an elastic membrane and being configured to dose the second volume by controlling an amount of deformation of the elastic membrane.
In some embodiments, the fluid driving method further comprises, after the mixture of the first fluid and the second fluid reaches a predefined volume in the second dosing section: filling a third quantitative portion by changing the amount of deformation of the elastic membrane to drive the mixture through a fourth port, the fluid flowing out of the third quantitative portion during filling flowing into a second discharge portion; and detecting the mixture in the third quantitative section, wherein the third quantitative section has a third volume and is configured to quantitatively control the volume of the mixture in the third quantitative section.
According to the microfluidic substrate, the microfluidic device and the fluid driving method provided by the embodiment of the disclosure, under the condition that a flow sensor is not needed, the volume of a first fluid (for example, a sample to be detected) can be accurately controlled by using the first quantitative part, and meanwhile, the use volume of the first fluid is reduced, so that the microfluidic substrate, the microfluidic device and the fluid driving method are simple in structure and convenient to operate. Meanwhile, under the condition that a flow sensor is not needed, the volume of a mixture (such as a diluted sample) of the first fluid and the second fluid (such as diluent) can be accurately controlled by the second quantitative portion comprising the elastic membrane, the structure is simple, and the operation is convenient. The embodiment of the disclosure can realize operations such as quantitative transportation, dilution mixing, reaction and the like of the fluid, does not need a complex external sensor and a fluid driving control device, improves the integration level of the system, and reduces the process complexity and the cost of the system. In addition, in the embodiment of the present disclosure, the second covering part is taken as a consumable part, so that the risks of sample contamination and biological exposure are reduced, and a complicated cleaning step is omitted.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present disclosure, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is apparent that the drawings in the following description are only some embodiments of the present disclosure.
Fig. 1 is a schematic structural diagram of a microfluidic substrate according to an embodiment of the present disclosure;
FIG. 2 is a schematic cross-sectional view of the second quantitative section taken along line A-B in FIG. 1;
fig. 3 is a schematic structural view of a body portion of a microfluidic substrate according to an embodiment of the present disclosure;
fig. 4 is a schematic structural view of a second cover of a microfluidic substrate according to an embodiment of the present disclosure;
fig. 5 is a schematic structural view of a fastener of a microfluidic substrate according to an embodiment of the present disclosure;
fig. 6 is a schematic structural view of a first cover of a microfluidic substrate according to an embodiment of the present disclosure;
fig. 7 is a schematic structural view of a bonding portion of a microfluidic substrate according to an embodiment of the present disclosure; and (c) and (d).
Fig. 8 is a perspective schematic view of a microfluidic substrate according to an embodiment of the present disclosure.
Detailed Description
To make the objects, technical solutions and advantages of the embodiments of the present disclosure more clear, the technical solutions of the embodiments of the present disclosure will be described in further detail below with reference to the accompanying drawings.
At present, in the process of using the microfluidic device, after a sample is injected into a fluid space of the microfluidic device, the volume usage participating in a reaction cannot be accurately quantified in a simple manner without a sensor. The addition of the fluid flow sensor increases the cost of the device as a consumable and the complexity of the device, and is obviously not favorable for the integration, miniaturization and productization of the analysis and detection device based on the microfluidic device.
Therefore, how to quantify the fluid to be measured without the aid of a fluid flow sensor, so as to facilitate subsequent steps such as mixing and detection, and the like, is a technical problem to be solved. An object of the present disclosure is to develop a microfluidic substrate, a microfluidic device, and a fluid driving method for the microfluidic substrate that perform fluid quantification without the aid of a fluid flow sensor.
Fig. 1 depicts a schematic structural diagram of a microfluidic substrate according to an embodiment of the present disclosure. The fluid space 100 of the microfluidic substrate comprises a first quantitative portion 110. The first dosing portion 110 has a first volume and is configured to provide a first volume of the first fluid equal to the first volume. For example, when the first quantitative portion 110 is a rectangular parallelepiped, the first volume (i.e., first volume) V1 is calculated according to equation (1):
V1=L1*W1*D1 （1），
wherein L1 is the length of the cuboid, W1 is the width of the cuboid, and D1 is the height or depth of the cuboid.
The fluid space 100 of the microfluidic substrate further comprises a first inlet 120 for adding a first fluid to the fluid space, a second inlet 130 for adding a second fluid to the fluid space and a first outlet 140 which may contain a quantity of fluid. The first dosing portion 110 includes a first port 112 and a second port 114. The first dosing portion 110 is in fluid communication with the first feed portion 120 through a first port 112 and in fluid communication with the second feed portion 130 and the first discharge portion 140 through a second port 114, respectively. The first feed 120 is configured to provide a first fluid having a volume greater than the first volume V1 to the first dosing portion 110 through the first port 112, and the second feed 130 is configured to provide a second fluid. It should be understood that the present disclosure does not limit the shape of the cross-section of the first dosing portion 110, the first feeding portion 120, the second feeding portion 130, and the first discharging portion 140 in the fluid flow direction. The cross-section may be square, rectangular, circular, oval, irregular, etc.
In some embodiments, the fluid space 100 of the microfluidic substrate is formed by the body portion in conformity with the first cover. In other words, an open channel may be formed on one side surface of the main body part to a certain depth, and then the first cover member is bonded and sealed with the side surface of the main body part, so that both may surround and form the fluid space.
In some embodiments, as shown in fig. 1, the fluid space 100 of the microfluidic substrate further includes a second quantifying portion 150 for quantitatively controlling a volume of a mixture of the first fluid and the second fluid. The second metering section 150 includes a third port 152 and a fourth port 154, the third port 152 being in fluid communication with the first port 112.
The second quantitative section 150 is configured to quantitatively control the volume of the fluid contained therein by changing its volume. For example, the second dosing section 150 may comprise a membrane pump chamber comprising an elastic membrane to control the volume change in the chamber and to drive the flow of fluid. Fig. 2 is a schematic sectional view of the second quantitative section taken along line a-B in fig. 1. As shown in fig. 2, the second quantitative section 150 includes a main body portion 210 of the microfluidic substrate and an elastic membrane 230, and the second quantitative section 150 is configured to change a volume of the membrane chamber 220 by changing a deformation amount of the elastic membrane 230, thereby driving a fluid into and out of the membrane chamber 220 through the third port 152 and the fourth port 154. When the elastic membrane 230 is pulled down, for example by applying a negative pressure to the elastic membrane 230, fluid may enter the membrane cavity 220 through the third port 152 if the fourth port 154 is closed. At this time, the fluid receiving space enclosed by the elastic membrane 230 and the main body part 210 has a second volume, thereby providing a second volume of fluid equal to the second volume. In some embodiments, when the second volume is in the shape of a portion of a sphere (a segment), the second volume (i.e., the second volume) V2 can be quantitatively calculated according to the following equation (2) for the computation of the segment volume:
V2=πH(3D2+4H2)/24 （2）
where D is the diameter of the cross section where the fluid contacts the body portion 210, and H is the distance of the elastic membrane 230 from the cross section along the center normal direction of the cross section where the fluid contacts the body portion 210.
In some embodiments, the first cover may include an elastic film 230. In other words, the elastic film 230 may be a part of the first cover.
As shown in fig. 1, the fluid space 100 of the microfluidic substrate may further include a third quantitative section 160, the third quantitative section 160 having a third volume V3 and configured to quantitatively control a volume of the fluid in the third quantitative section. For example, when the third quantitative section 160 is a rectangular parallelepiped, the third volume V3 is calculated according to equation (3):
V3=L3*W3*D3 （3）
wherein L3 is the length of the cuboid, W3 is the width of the cuboid, and D3 is the height or depth of the cuboid.
The third metering section 160 includes fifth and sixth ports 162 and 164, with the fifth port 162 being in fluid communication with the fourth port 154. In some embodiments, the third quantification section 160 includes a detection site 166 to detect a mixture of both the first fluid and the second fluid. For example, the detection sites 166 may include antibodies or antigens, or the like, to biodetect a mixture of both the first and second fluids.
In some embodiments, the fluid space 100 of the microfluidic substrate further comprises a filter membrane 180 located between the first feed section 120 and the first port 112 of the first dosing section 110 for filtering the first fluid. For example, when the first fluid is blood, filter membrane 180 may be a conventional blood filtration membrane for filtering cells and other large molecules in the blood.
In some embodiments, the fluid space 100 of the microfluidic substrate further comprises a second drain 170, the second drain 170 being in fluid communication with the sixth port 164 and configured to contain fluid flowing out of the third dosing section 160.
Fig. 3 to 7 are schematic structural views of the main body part 210, the second cover 300, the fastener 400, the first cover 500, and the bonding part 600 of the microfluidic substrate according to an embodiment of the present disclosure. As shown in fig. 3, the first feeding part 120, the second feeding part 130, the first discharging part 140, and the second discharging part 170 may penetrate upper and lower surfaces of the body part 210. The main body part 210 may include a channel formed on one side surface with a certain depth for forming the fluid space 100, i.e., each functional part (e.g., a first quantitative part, a first feeding part, a second feeding part, a first discharging part, a second quantitative part, a third quantitative part, a second discharging part, etc.) and a channel connecting different functional parts, etc., in cooperation with the first cover 500. The fluid space 100 may be used for sample introduction, mixing, dilution, antigen-antibody reaction, etc. The body portion 210 may also include mounting openings 310, such as threaded holes, for attachment. The body portion 210 is made of plastic such as Polystyrene (PS), and may be manufactured through an injection molding process. The microfluidic substrate may further comprise a second cover 300 on a side of the body portion 210 remote from the first cover 500 for sealing the fluid space. As shown in fig. 4, the second cover 300 may include first, second, third, and fourth seals 320, 330, 340, and 370 that cooperate with the first and second inlets 120, 130, 140, and 170, respectively. In some embodiments, the second cover 300 can be a consumable component, reducing the risk of sample contamination and biological exposure, eliminating complex cleaning steps. In some embodiments, the first seal 320, the second seal 330, the third seal 340, and the fourth seal 370 may seal or open the first feed 120, the second feed 130, the first discharge 140, and the second discharge 170, respectively, to the outside air, as desired. The second cover 300 may be made of, for example, silicon rubber. The microfluidic substrate may further include a fastener 400, the fastener 400 being used to fasten the second cover 300 to the body portion 210. For example, the fastener 400 may include a mounting member 410 for cooperating with the mounting opening 310 to secure. For example, the mounting member 410 may be a screw, a snap, or the like. The fastener 400 may be made of ABS plastic. By using the second cover 300 and the fastener 400, the fluid space of the microfluidic substrate can be controllably closed and opened, so that the fluid in the fluid space can be driven to flow directionally.
Fig. 6 shows a schematic view of a first cover 500, wherein the first cover 500 may be a multilayer composite. For example, the first cover member 500 may include a hydrophilic layer and an elastic layer. The lyophilic layer provides good fluid wetting with the fluid, while the elastic layer has good elasticity and toughness. The elastic layer can play a role in quantitatively pumping fluid by virtue of low-frequency up-and-down single motion, and can play a role in mixing fluid in the membrane cavity by virtue of high-frequency up-and-down motion. For example, in the case where the first cover member 500 serves as the elastic film 230 of the second quantitative portion 150, the elastic layer may provide a good elastic effect. In an exemplary embodiment, the lyophilic layer is made of, for example, PS, and the elastic layer is made of, for example, polyethylene terephthalate (PET). The microfluidic substrate may further include a bonding portion 600. The coupling portion 600 serves to couple the first cover 500 to the main body portion 210. For example, the bonding portion 600 may be a double-sided tape, on which a corresponding relief space is reserved for the fluid space.
Fig. 8 shows a schematic perspective view of a microfluidic substrate after assembly is complete according to an embodiment of the present disclosure. The microfluidic substrate includes a main body portion 210, a second cover 300, a fastener 400, a first cover 500, and a coupling portion 600.
Embodiments of the present disclosure also disclose a microfluidic device, comprising: the microfluidic substrate is described above. The micro-fluidic device may further include a control means for controlling the second cover member 300 such that the first feeding portion 120, the second feeding portion 130, the first discharging portion 140, and the second discharging portion 170 are sealed or opened to the external air, an injection means for adding a fluid to the first feeding portion 120 and the second feeding portion 130, and a pressure control means for applying positive and negative pressure to the elastic membrane 230 of the second quantitative portion 150 to deform the elastic membrane 230 such that the fluid enters and exits the second quantitative portion 150, and the like. These means are known to the person skilled in the art and will not be described in further detail.
Embodiments of the present disclosure also disclose a fluid driving method for a microfluidic substrate, including:
s701: driving a first fluid flow through the first port to fill the first metering section, excess first fluid flowing into the first discharge section during filling; wherein the first volume has a first volume and is configured to provide a first volume of the first fluid equal to the first volume.
The fluid drive method further includes, after driving the first fluid flow through the first port to fill the first volume:
s702: the second fluid is driven to flow through the second port and enter the first quantitative portion, and meanwhile the first fluid in the first quantitative portion flows to the second quantitative portion through the first port.
The fluid drive method further includes, after driving the second fluid flow through the second port into the first volume:
s703: driving the first fluid and the second fluid into the second dosing section until the mixture of the first fluid and the second fluid reaches a predefined volume in the second dosing section;
wherein the second dosing section comprises a membrane pump chamber having a second volume, the membrane pump chamber comprising an elastic membrane and being configured to dose the second volume by controlling an amount of deformation of the elastic membrane.
The fluid driving method further includes, after the mixture of the first fluid and the second fluid reaches the predefined volume in the second dosing section:
s704: filling the third quantitative portion by driving the mixture through the fourth port by changing the amount of deformation of the elastic membrane, the fluid flowing out of the third quantitative portion during filling flowing into the second discharge portion; and
s705: detecting the mixture in the third quantitative section;
wherein the third dosing section has a third volume and is configured to dose control the volume of the mixture in the third dosing section.
Specifically, a fluid driving method according to an embodiment of the present disclosure is described below in conjunction with the structures shown in fig. 1 to 8.
After the first fluid introduced from the first inlet portion 120 is filtered, the first fluid is driven from the first port 112 into the first quantitative portion 110 having the first volume by the external motor, so that the first fluid is overfilled in the first quantitative portion 110 and overflows from the second port 114 to the first outlet portion 140. At this time, the first discharge part 140 is opened to the external air, and the second feeding part 130 and the second quantitative part 150 are sealed, so that the first fluid does not flow to the passage of the second feeding part 130. The sealing method of the first feeding portion 120, the second feeding portion 130 and the first discharging portion 140 may be, for example, locking a driving motor of the liquid injection piston push rod by means of a control device of the microfluidic device, or sealing by means of the second cover 300. The sealing of the second dosing part 150 may for example be a fixing of the elastic membrane 230 or a maintaining of a certain pressure by means of a control device.
The first quantitative part 110 realizes the first quantitative determination by providing a microchannel in which a fluid flows bidirectionally on the microfluidic substrate and intercepting the fluid in the microchannel of a certain length. By excluding fluid from the channel beyond the first volume 110, fluid in the channel is taken at an intermediate fixed length to precisely control the volume of fluid participating in the reaction. The channel design of the microfluidic substrate is used for accurate quantification, the using volume of the fluid is reduced, the amount of the fluid participating in the reaction is accurately controlled, the detection failure caused by less sampling amount of the fluid is reduced, and the detection result is more accurate.
Then, the second fluid is introduced into the second feeding portion 130, and the second fluid is driven to flow toward the first quantitative portion 110 through the second port 114 by deforming the elastic membrane 230 of the second quantitative portion 150. Alternatively, the application of pressure to the second fluid by second charging portion 130 drives the second fluid through second port 114 toward first dosing portion 110. At this time, the first feeding portion 120 and the first discharging portion 140 are sealed. Therefore, the second fluid drives the first fluid in the first quantitative portion 110 into the second quantitative portion 150. At this time, the second discharge portion 170 is sealed, and the sealing method may be the same as that of the first discharge portion 140, for example. Therefore, the mixture of the first fluid and the second fluid will be accumulated in the second quantitative section 150. Since the second volume of the second quantitative section 150 can be precisely controlled by controlling the amount of deformation of the elastic membrane 230, the volume of the mixture of the first fluid and the second fluid can be correspondingly controlled to be equal to the second volume V2 of the second volume, and since the volume of the first fluid is controlled to be the first volume V1 in the previous step, the volume of the second fluid is V2 to V1. Accordingly, the ratio of the first fluid and the second fluid can be controlled. For example, the first fluid may be the fluid to be detected and the second fluid may be a diluent.
The second quantitative section 150 determines a second volume contained by the elastic membrane 230 of the second quantitative section 150 once deformed based on the cross section and the pull-down depth of the second quantitative section 150 by the deformation of the elastic membrane 230, thereby realizing a second quantitative determination. The second quantification serves to determine the volume of the mixture of the first fluid and the second fluid. The second quantitative determination may be precisely controlled by the pull-down depth or the number of times of the pull-down of the elastic membrane 230, and the quantitative determination may be controlled by controlling the pull-down depth of the elastic membrane 230 when the volume of the mixture of the first fluid and the second fluid is smaller than the maximum second volume of the second quantitative portion 150, or may be determined by pulling down the elastic membrane for a plurality of full strokes. The second quantitative part 150 is used for carrying out the second quantitative operation, the structure is simple, and the operation is convenient.
The elastic film 230 of the second quantitative section 150 may also function as a mixed fluid. For example, the first fluid and the second fluid may be diluted and mixed by the high frequency (e.g., 0.5 times/second) up and down movement of the elastic membrane 230, and the fixed amount of the first fluid may be diluted by the fixed amount of the second fluid after the mixing is completed.
Finally, the second discharge portion 170 is opened to the external air, the first feeding portion 120, the second feeding portion 130 and the first discharge portion 140 are sealed, the elastic membrane 230 is pushed up or the elastic membrane 230 is restored to the pre-deformation shape, and the mixed first fluid and second fluid may be driven into the third quantitative portion 160 having the third volume V3 through the fifth port 162. The third quantitative section 160 may have a pre-embedded detection site, such as a labeled antibody, where an antigen-antibody reaction is performed, i.e., a mixture of the first fluid and the second fluid to be quantified is detected. Alternatively, a third volume of fluid may be driven to flow back and forth in the third metering section 160 by pulling the elastic membrane 230 up and down, thereby sufficiently performing the mixing reaction. Optionally, the detection site after the reaction can be further detected, such as optical detection.
The third quantifying unit 160 may quantify the volume of the fluid involved in the detection reaction, i.e., a third quantifying. By combining the fixed volume third quantifying unit 160 and a predetermined amount of the assay site, the quantification of the reactant in the assay process can be achieved. And the accurate quantification of the whole detection process is realized by three times of quantification.
According to the microfluidic substrate, the microfluidic device and the fluid driving method provided by the embodiment of the disclosure, under the condition that a flow sensor is not needed, the volume of a first fluid (for example, a sample to be detected) can be accurately controlled by using the first quantitative part, and meanwhile, the use volume of the first fluid is reduced, so that the microfluidic substrate, the microfluidic device and the fluid driving method are simple in structure and convenient to operate. Meanwhile, under the condition that a flow sensor is not needed, the volume of a mixture (such as a diluted sample) of the first fluid and the second fluid (such as diluent) can be accurately controlled by the second quantitative portion comprising the elastic membrane, the structure is simple, and the operation is convenient. The embodiment of the disclosure can realize operations such as quantitative transportation, dilution mixing, reaction and the like of the fluid, does not need a complex external sensor and a fluid driving control device, improves the integration level of the system, and reduces the process complexity and the cost of the system. In addition, in the embodiment of the present disclosure, the second covering member can be used as a consumable part, so that the risks of sample contamination and biological exposure are reduced, and a complicated cleaning step is omitted.
As will be apparent to those skilled in the art, many different ways of performing the methods of the embodiments of the present disclosure are possible. For example, the order of the steps may be changed, or some of the steps may be performed in parallel. In addition, other method steps may be inserted between the steps. The intervening steps may represent modifications to the methods, such as those described herein, or may be unrelated to the methods. Furthermore, a given step may not have been completely completed before the next step begins.
Various modifications and alterations of this disclosure may be made by those skilled in the art without departing from the spirit and scope of this disclosure. Thus, if such modifications and variations of the present disclosure fall within the scope of the claims of the present disclosure and their equivalents, the present disclosure is intended to include such modifications and variations as well.
Claims (14)
1. A microfluidic substrate comprising: a first volume having a first volume and configured to provide a first volume of a first fluid equal to the first volume,
the microfluidic substrate further comprises a first feeding part, a second feeding part and a first discharging part,
wherein the first dosing portion comprises a first port and a second port,
the first metering portion being in fluid communication with the first feed portion through the first port and in fluid communication with the second feed portion and the first discharge portion through the second port, respectively,
the microfluidic substrate further comprises a second quantification section for quantitatively controlling a volume of a mixture of both the first fluid and the second fluid, wherein the second quantification section comprises a third port in fluid communication with the first port.
2. The microfluidic substrate of claim 1, wherein the first feed portion is configured to provide a first fluid greater than the first volume to the first quantitative portion through the first port, and the second feed portion is configured to provide a second fluid.
3. The microfluidic substrate according to claim 2, the second quantifying portion comprising a membrane pump chamber having a second volume, the membrane pump chamber comprising an elastic membrane and configured to quantify the second volume by controlling an amount of deformation of the elastic membrane.
4. The microfluidic substrate according to claim 3, wherein the second quantitative section comprises a fourth port.
5. The microfluidic substrate according to claim 4, further comprising a third quantitative section having a third volume and configured to quantitatively control a volume of the fluid in the third quantitative section.
6. The microfluidic substrate of claim 5, wherein the third quantification section comprises a detection site and the third quantification section comprises a fifth port and a sixth port, the fifth port in fluid communication with the fourth port.
7. The microfluidic substrate according to claim 6, further comprising a second vent in fluid communication with the sixth port and configured to contain fluid flowing out of the third dosing section.
8. The microfluidic substrate according to claim 7, further comprising a main body part and a first cover, wherein the main body part and the first cover are attached to form the first quantitative part, the first feeding part, the second feeding part, the first discharging part, the second quantitative part, the third quantitative part, and the second discharging part.
9. The microfluidic substrate of claim 8, wherein the first cover comprises a composite structure of a hydrophilic layer and an elastic layer.
10. The microfluidic substrate according to claim 9, further comprising a second cover on a side of the main body portion away from the first cover, the second cover for sealing one or more of the first feed portion, the second feed portion, the first drain portion, and the second drain portion.
11. A microfluidic device comprising:
the microfluidic substrate according to any one of claims 1-10.
12. A fluid driving method for a microfluidic substrate according to any one of claims 1-10, comprising:
driving a first fluid flow through the first port to fill the first metering section, excess first fluid flowing into the first discharge section during filling; wherein the first volume has a first volume and is configured to provide a first volume of a first fluid equal to the first volume,
the fluid drive method further includes, after driving the first fluid flow through the first port to fill the first volume:
the second fluid is driven to flow through the second port and enter the first quantitative portion, and meanwhile the first fluid in the first quantitative portion flows to the second quantitative portion through the first port.
13. The fluid driving method of claim 12, further comprising, after driving a second fluid flow through a second port into the first volume:
driving the first fluid and the second fluid into said second dosing section until the mixture of the first fluid and the second fluid reaches a predefined volume in said second dosing section,
wherein the second dosing section comprises a membrane pump chamber having a second volume, the membrane pump chamber comprising an elastic membrane and being configured to dose the second volume by controlling an amount of deformation of the elastic membrane.
14. The fluid driving method according to claim 13, further comprising, after the mixture of the first fluid and the second fluid reaches a predefined volume in the second dosing section:
filling a third quantitative portion by changing the amount of deformation of the elastic membrane to drive the mixture through a fourth port, the fluid flowing out of the third quantitative portion during filling flowing into a second discharge portion; and
detecting the mixture in the third quantitative section,
wherein the third dosing section has a third volume and is configured to dose control the volume of the mixture in the third dosing section.
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| CN201910988391.5A CN111617812B (en) | 2019-10-17 | 2019-10-17 | Microfluidic substrate, fluid driving method thereof and microfluidic device |
| PCT/CN2020/117024 WO2021073381A1 (en) | 2019-10-17 | 2020-09-23 | Microfluidic substrate and fluid driving method therefor, and microfluidic device |
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| CN201910988391.5A CN111617812B (en) | 2019-10-17 | 2019-10-17 | Microfluidic substrate, fluid driving method thereof and microfluidic device |
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| EP3997159A1 (en) | 2019-07-10 | 2022-05-18 | Boston Materials, Inc. | Systems and methods for forming short-fiber films, composites comprising thermosets, and other composites |
| CN111617812B (en) * | 2019-10-17 | 2021-12-03 | 北京京东方健康科技有限公司 | Microfluidic substrate, fluid driving method thereof and microfluidic device |
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| WO2021073381A1 (en) | 2021-04-22 |
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