CN113814011A - Microfluid sample injection device and method based on hydrophobic capillary - Google Patents
Microfluid sample injection device and method based on hydrophobic capillary Download PDFInfo
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- CN113814011A CN113814011A CN202111087833.2A CN202111087833A CN113814011A CN 113814011 A CN113814011 A CN 113814011A CN 202111087833 A CN202111087833 A CN 202111087833A CN 113814011 A CN113814011 A CN 113814011A
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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
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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
- B01L3/02—Burettes; Pipettes
- B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
Abstract
The invention discloses a microfluidic sample injection device and method based on a hydrophobic capillary tube, and the microfluidic sample injection device comprises a water phase injector, an oil phase injector, a water phase sample pipeline, an oil phase sample pipeline and a droplet generation module, wherein an injection port of the water phase injector is connected with an input end of the water phase sample pipeline, an output end of the water phase sample pipeline is connected with the droplet generation module, an injection port of the oil phase injector is connected with an input end of the oil phase sample pipeline, an output end of the oil phase sample pipeline is connected with the droplet generation module, and the water phase sample pipeline and the oil phase sample pipeline are hydrophobic capillary tubes. The invention can store multiple sections of water phase samples through the hydrophobic capillary, prevent the fusion of multiple water phase samples and can be widely applied to the technical field of microfluidics.
Description
Technical Field
The invention relates to the technical field of microfluidics, in particular to a microfluid sample injection device and method based on a hydrophobic capillary tube.
Background
Droplet microfluidics has become a widely used multifunctional method that enables independent control of each droplet. Droplet generation is based on the principle of fluid instability, in microfluidic devices, microdroplets are generated by introducing one fluid (discrete phase) into another (continuous phase) immiscible fluid. In the existing device, only one aqueous phase sample can be injected into a low-density microfluidic discrete phase at a time, and if multiple aqueous phase samples are injected, the aqueous phase samples can be gathered and fused together. In addition, for the continuous phase with low surface free energy, the oil phase sample is dispersed into many small sample particles due to the action of large surface tension after being sucked into the closed container from the syringe needle, so that the sample discontinuity is caused.
Disclosure of Invention
In view of this, the embodiments of the present invention provide a simple and practical microfluidic sample injection device and method based on a hydrophobic capillary, so as to achieve simultaneous loading of multiple samples.
In one aspect, the invention provides a microfluidic sample injection device based on a hydrophobic capillary tube, which comprises a water phase injector, an oil phase injector, a water phase sample pipeline, an oil phase sample pipeline and a droplet generation module, wherein an injection port of the water phase injector is connected with an input end of the water phase sample pipeline, an output end of the water phase sample pipeline is connected with the droplet generation module, an injection port of the oil phase injector is connected with an input end of the oil phase sample pipeline, an output end of the oil phase sample pipeline is connected with the droplet generation module, and the water phase sample pipeline and the oil phase sample pipeline are hydrophobic capillary tubes.
Optionally, the injection port of the aqueous phase injector is connected with the input end of the aqueous phase sample pipeline, and comprises:
and sealing the joint of the injection port of the water phase injector and the water phase sample pipeline by using hot melt adhesive.
Optionally, the injection port of the oil phase injector is connected with the input end of the oil phase sample pipeline, and comprises:
and sealing the joint of the injection port of the oil phase injector and the oil phase sample pipeline by using hot melt adhesive.
Optionally, the aqueous sample conduit comprises a U-shaped conduit.
Optionally, the hydrophobic capillary comprises at least one of a polytetrafluoroethylene capillary, a perfluoroethylene propylene copolymer capillary, a polyetheretherketone capillary, and a polyvinyl chloride capillary.
Optionally, the aqueous phase sample conduit stores a plurality of sections of aqueous phase sample.
Optionally, the droplet generation module comprises at least one of a microfluidic droplet chip, a cross-flow capillary, a flow focused-flow capillary, and a coaxial focused-flow capillary.
In another aspect, an embodiment of the present invention further provides a microfluidic sample injection method based on a hydrophobic capillary, which is applied to the apparatus as described in any one of the above, including:
sucking a plurality of sections of water phase samples and oil phase samples into a water phase sample pipeline through a water phase injector, wherein each section of water phase sample in the water phase sample pipeline is separated by the oil phase sample;
sucking the oil phase sample into an oil phase sample pipeline through an oil phase injector;
the micro-droplets are generated by respectively connecting the water phase injector and the oil phase injector through the droplet generation module.
Optionally, before the plurality of sections of the aqueous phase sample and the oil phase sample are sucked into the aqueous phase sample pipeline by the aqueous phase injector, the method further comprises:
injecting the oil phase sample into the water phase injector and the oil phase injector, and discharging air inside the water phase injector and the oil phase injector.
Optionally, drawing the plurality of sections of the aqueous phase sample and the oil phase sample into the aqueous phase sample line by an aqueous phase syringe, comprising:
the water phase sample is subjected to the dominant action of capillary force in the water phase sample pipeline and is stored in the water phase sample pipeline in a liquid section mode.
Compared with the prior art, the invention adopting the technical scheme has the following technical effects: the device comprises a water phase injector, an oil phase injector, a water phase sample pipeline, an oil phase sample pipeline and a liquid drop generation module, wherein an injection port of the water phase injector is connected with an input end of the water phase sample pipeline, an output end of the water phase sample pipeline is connected with the liquid drop generation module, an injection port of the oil phase injector is connected with an input end of the oil phase sample pipeline, an output end of the oil phase sample pipeline is connected with the liquid drop generation module, and the water phase sample pipeline and the oil phase sample pipeline are hydrophobic capillaries. The invention can store multiple sections of water phase samples through the hydrophobic capillary tube, and prevent fusion of multiple water phase samples.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
FIG. 1 is a schematic diagram of a microfluidic sample injection device based on a hydrophobic capillary according to an embodiment of the present invention;
fig. 2 is a flow chart of a microfluidic sample injection method based on a hydrophobic capillary according to an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present application more apparent, the present application is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present application and are not intended to limit the present application.
The embodiment of the invention provides a micro-fluid sample injection device based on a hydrophobic capillary tube, which comprises a water phase injector, an oil phase injector, a water phase sample pipeline, an oil phase sample pipeline and a liquid drop generation module, wherein an injection port of the water phase injector is connected with the input end of the water phase sample pipeline, the output end of the water phase sample pipeline is connected with the liquid drop generation module, the injection port of the oil phase injector is connected with the input end of the oil phase sample pipeline, the output end of the oil phase sample pipeline is connected with the liquid drop generation module, and the water phase sample pipeline and the oil phase sample pipeline are hydrophobic capillary tubes.
Referring to fig. 1, an aqueous phase injector 1 is used for sucking an aqueous phase sample into an aqueous phase sample pipeline 3, the aqueous phase sample pipeline 3 is used for storing a plurality of sections of aqueous phase samples, and the aqueous phase samples can be one aqueous phase sample or a plurality of aqueous phase samples. The oil phase injector 2 is used to draw the oil phase sample into the oil phase sample pipe 4, and the oil phase sample pipe 4 is used to store and transport the oil phase. The droplet generation module 5 is used for connecting the water phase sample pipeline 3 and the tail end of the oil phase sample pipeline 4 to generate water-in-oil micro droplets. The water phase sample pipeline 3 and the oil phase sample pipeline 4 in the device are hydrophobic capillaries, and due to the hydrophobicity and the non-adhesiveness of the hydrophobic capillaries, the adhesion of a water phase sample is avoided, and a multi-section water phase sample can be stored better. The water phase injector 1 and the oil phase injector 2 are used for extracting, storing and delivering continuous water phase or oil phase, and then the flow of liquid in the injector and the pipeline and the flow of liquid drops after the liquid drops are generated by the liquid drop generation module 5 are driven under the action of external power, wherein the flow speed is determined by the flow rates of the water phase injector 1 and the oil phase injector 2. The aqueous phase sample pipe 3 is used for storing and transporting aqueous phase samples to be subjected to biochemical reaction, and each aqueous phase sample is separated by oil phase. The droplet generation module 5 utilizes the shearing force of the oil phase relative to the water phase sample to shear the water phase sample into independent and monodisperse droplets for carrying out independent biochemical reactions.
Further as a preferred embodiment, the injection port of the aqueous phase injector is connected with the input end of the aqueous phase sample pipeline, and comprises:
and sealing the joint of the injection port of the water phase injector and the water phase sample pipeline by using hot melt adhesive.
Wherein, use the hot melt adhesive to seal and fix at the junction of the injection port of aqueous phase syringe and aqueous phase sample pipeline, can prevent weeping and pipeline from droing.
Further as a preferred embodiment, the injection port of the oil phase injector is connected with the input end of the oil phase sample pipeline, and comprises:
and sealing the joint of the injection port of the oil phase injector and the oil phase sample pipeline by using hot melt adhesive.
Wherein, use the hot melt adhesive to seal and fix at the junction of the injection port of oil phase syringe and oil phase sample pipeline, can prevent that weeping and pipeline from droing.
Further as a preferred embodiment, the aqueous phase sample conduit comprises a U-shaped conduit.
Wherein, can better save multistage aqueous phase sample through U type pipeline.
Further as a preferred embodiment, the hydrophobic capillary comprises at least one of a polytetrafluoroethylene capillary, a perfluoroethylene propylene copolymer capillary, a polyetheretherketone capillary and a polyvinylchloride capillary.
The polytetrafluoroethylene capillary tube, the perfluoroethylene propylene copolymer capillary tube, the polyether-ether-ketone capillary tube and the polyvinyl chloride capillary tube have the advantages of strong hydrophobicity and low friction coefficient, can replace a closed container to load a sample, and avoids the sample from being remained, discretized, mixed with air or cross-contaminated in the closed container.
Further preferably, the aqueous phase sample line stores a plurality of sections of the aqueous phase sample.
In the case of storing a water phase sample in a sealed container, only one sample can be injected at a time, multiple sections of water phase samples can be focused and fused together, and if air separation is used, the problem of air mixing can occur. If the oil phase separation is used, the water phase sample in the sealed container can float under the action of the buoyancy of the oil phase, so that the operation difficulty is increased. The water phase sample pipeline using the hydrophobic capillary can weaken the influence of buoyancy on the water phase sample in the oil phase by utilizing the principle that the capillary force of the water phase sample in the hydrophobic capillary is in inverse proportion to the radius of the capillary, so that a plurality of water phase samples can be sequentially taken in a liquid section mode and stored in the water phase sample pipeline.
Further as a preferred embodiment, the droplet generation module comprises at least one of a microfluidic droplet chip, a cross-flow capillary, a flow focused-flow capillary and a coaxial focused-flow capillary.
The liquid drop generating module is used for connecting the water phase sample pipeline and the oil phase sample pipeline, and can generate monodisperse liquid drops in various modes such as a microfluidic liquid drop chip, a cross-flow capillary tube, a coaxial focusing flow capillary tube, a flowing focusing flow capillary tube and the like.
Referring to fig. 2, an embodiment of the present invention further provides a microfluidic sample injection method based on a hydrophobic capillary, applied to the apparatus as described above, including:
sucking a plurality of sections of water phase samples and oil phase samples into a water phase sample pipeline through a water phase injector, wherein each section of water phase sample in the water phase sample pipeline is separated by the oil phase sample;
sucking the oil phase sample into an oil phase sample pipeline through an oil phase injector;
the micro-droplets are generated by respectively connecting the water phase injector and the oil phase injector through the droplet generation module.
Further as a preferred embodiment, before the plurality of sections of the aqueous phase samples and the oil phase samples are sucked into the aqueous phase sample pipeline by the aqueous phase injector, the method further comprises the following steps:
injecting the oil phase sample into the water phase injector and the oil phase injector, and discharging air inside the water phase injector and the oil phase injector.
Wherein the fluorinated oil as a continuous phase is injected into the aqueous phase injector and the oil phase injector, and the air inside the injectors is discharged. The syringe material that prior art used is mostly plastics (polypropylene) and glass, and anterior segment injection site is the stainless steel needle, and the surface hydrophobicity is not good, and the aqueous phase sample is easy to remain and adhere inside the syringe, causes the aqueous phase sample to run off. The oil phase wraps the water phase to form water-in-oil droplets, each droplet is an independent micro-reaction container, the oil phase plays a role in bearing and protecting, air can be prevented from being mixed after air is exhausted, and water phase sample residues can be removed.
Further, as a preferred embodiment, the method for sucking the multiple sections of the aqueous phase sample and the oil phase sample into the aqueous phase sample pipeline by the aqueous phase injector comprises the following steps:
the water phase sample is subjected to the dominant action of capillary force in the water phase sample pipeline and is stored in the water phase sample pipeline in a liquid section mode.
Wherein, the capillary force is the force which can cause the liquid which is wet or non-wet with the tube wall to naturally rise or fall in the capillary. This force is directed in the direction in which the concave surface of the liquid is oriented, and its magnitude is proportional to the surface tension of the liquid and inversely proportional to the capillary radius. The aqueous sample is stored in the aqueous sample channel in the form of a liquid segment by capillary forces in the hydrophobic capillary.
The embodiment process of the microfluidic sample injection device based on the hydrophobic capillary specifically comprises the following steps:
firstly, the water phase sample pipeline and the oil phase pipeline are respectively connected with outlet needle heads of the water phase injector and the oil phase injector, and then are sealed and fixed by hot melt adhesive to prevent liquid leakage and pipeline falling. And (3) extracting the prepared first water phase sample by using a water phase injector and a water phase sample pipeline, extracting a small amount of oil phase, sequentially extracting a second water phase sample, a small amount of oil phase, a third water phase sample and a small amount of oil phase, and so on. And after the water phase sample is loaded, connecting the water phase sample pipeline and the oil phase sample pipeline into the liquid drop generation module. The injection pump is used for driving the water phase injector and the oil phase injector respectively at constant flow rate, so that the water phase sample and the oil phase are introduced into the droplet generation module, and micro-droplets with the size of microliter to picoliter are generated based on the fluid instability principle.
In the existing device, a water phase sample is generally injected into a closed container, a disposable medical syringe is used for loading the sample, and then the sample is introduced into a microfluidic chip or a pipeline by using a driving device such as a mechanical pump, a pneumatic pump, a peristaltic pump and the like.
In summary, the embodiments of the present invention have the following advantages:
(1) the invention adopts the hydrophobic capillary as the water phase sample pipeline, so that the water phase sample can be stably stored in the water phase sample pipeline.
(2) The invention adopts the oil phase as the isolation layer, can load various water phase samples into the water phase sample pipeline at the same time, and can prevent the cross contamination of various water phase samples.
(3) The invention adopts the hydrophobic capillary tube to store and convey the water phase sample, and can avoid sample consumption caused by the residue of the water phase sample in the injector.
In alternative embodiments, the functions/acts noted in the block diagrams may occur out of the order noted in the operational illustrations. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality/acts involved. Furthermore, the embodiments presented and described in the flow charts of the present invention are provided by way of example in order to provide a more thorough understanding of the technology. The disclosed methods are not limited to the operations and logic flows presented herein. Alternative embodiments are contemplated in which the order of various operations is changed and in which sub-operations described as part of larger operations are performed independently.
Furthermore, although the present invention is described in the context of functional modules, it should be understood that, unless otherwise stated to the contrary, one or more of the functions and/or features may be integrated in a single physical device and/or software module, or one or more functions and/or features may be implemented in separate physical devices or software modules. It will also be appreciated that a detailed discussion of the actual implementation of each module is not necessary for an understanding of the present invention. Rather, the actual implementation of the various functional modules in the apparatus disclosed herein will be understood within the ordinary skill of an engineer, given the nature, function, and internal relationship of the modules. Accordingly, those skilled in the art can, using ordinary skill, practice the invention as set forth in the claims without undue experimentation. It is also to be understood that the specific concepts disclosed are merely illustrative of and not intended to limit the scope of the invention, which is defined by the appended claims and their full scope of equivalents.
The functions, if implemented in the form of software functional units and sold or used as a stand-alone product, may be stored in a computer readable storage medium. Based on such understanding, the technical solution of the present invention may be embodied in the form of a software product, which is stored in a storage medium and includes instructions for causing a computer device (which may be a personal computer, a server, or a network device) to execute all or part of the steps of the method according to the embodiments of the present invention. And the aforementioned storage medium includes: a U disk, a removable hard disk, a Read-only Memory (ROM), a Random Access Memory (RAM), a magnetic disk or an optical disk, and other various media capable of storing program codes.
The logic and/or steps represented in the flowcharts or otherwise described herein, e.g., an ordered listing of executable instructions that can be considered to implement logical functions, can be embodied in any computer-readable medium for use by or in connection with an instruction execution system, apparatus, or device, such as a computer-based system, processor-containing system, or other system that can fetch the instructions from the instruction execution system, apparatus, or device and execute the instructions. For the purposes of this description, a "computer-readable medium" can be any means that can contain, store, communicate, propagate, or transport the program for use by or in connection with the instruction execution system, apparatus, or device.
More specific examples (a non-exhaustive list) of the computer-readable medium would include the following: an electrical connection (electronic device) having one or more wires, a portable computer diskette (magnetic device), a Random Access Memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber device, and a portable compact disc read-only memory (CDROM). Additionally, the computer-readable medium could even be paper or another suitable medium upon which the program is printed, as the program can be electronically captured, via for instance optical scanning of the paper or other medium, then compiled, interpreted or otherwise processed in a suitable manner if necessary, and then stored in a computer memory.
It should be understood that portions of the present invention may be implemented in hardware, software, firmware, or a combination thereof. In the above embodiments, the various steps or methods may be implemented in software or firmware stored in memory and executed by a suitable instruction execution system. For example, if implemented in hardware, as in another embodiment, any one or combination of the following techniques, which are known in the art, may be used: a discrete logic circuit having a logic gate circuit for implementing a logic function on a data signal, an application specific integrated circuit having an appropriate combinational logic gate circuit, a Programmable Gate Array (PGA), a Field Programmable Gate Array (FPGA), or the like.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
While embodiments of the invention have been shown and described, it will be understood by those of ordinary skill in the art that: various changes, modifications, substitutions and alterations can be made to the embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.
While the preferred embodiments of the present invention have been illustrated and described, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. The utility model provides a microfluid sampling device based on hydrophobic capillary, its characterized in that, includes aqueous phase syringe, oil phase syringe, aqueous phase sample pipeline, oil phase sample pipeline and droplet generation module, the injection port of aqueous phase syringe is connected the input of aqueous phase sample pipeline, the output of aqueous phase sample pipeline is connected the droplet generation module, the injection port of oil phase syringe is connected the input of oil phase sample pipeline, the output of oil phase sample pipeline is connected the droplet generation module, the aqueous phase sample pipeline with oil phase sample pipeline is hydrophobic capillary.
2. The hydrophobic capillary-based microfluidic sample introduction device according to claim 1, wherein the injection port of the aqueous phase injector is connected to the input end of the aqueous phase sample pipeline, and comprises:
and sealing the joint of the injection port of the water phase injector and the water phase sample pipeline by using hot melt adhesive.
3. The microfluidic sample introduction device based on the hydrophobic capillary tube as claimed in claim 1, wherein the injection port of the oil phase injector is connected to the input end of the oil phase sample pipeline, and comprises:
and sealing the joint of the injection port of the oil phase injector and the oil phase sample pipeline by using hot melt adhesive.
4. The hydrophobic capillary-based microfluidic sample introduction device according to claim 1, wherein the aqueous phase sample conduit comprises a U-shaped conduit.
5. The microfluidic sample injection device according to claim 1, wherein the hydrophobic capillary comprises at least one of a polytetrafluoroethylene capillary, a perfluoroethylene propylene copolymer capillary, a polyetheretherketone capillary, and a polyvinyl chloride capillary.
6. The hydrophobic capillary-based microfluidic sample introduction device according to claim 4, wherein the aqueous phase sample pipeline stores multiple sections of aqueous phase samples.
7. The hydrophobic capillary-based microfluidic sample introduction device according to claim 1, wherein the droplet generation module comprises at least one of a microfluidic droplet chip, a cross-flow capillary, a flow focused-flow capillary, and a coaxial focused-flow capillary.
8. A method for microfluidic sample injection based on hydrophobic capillary, applied to the device according to any one of claims 1 to 7, comprising:
sucking a plurality of sections of water phase samples and oil phase samples into the water phase sample pipeline through a water phase injector, wherein each section of the water phase samples in the water phase sample pipeline are separated through the oil phase samples;
sucking the oil phase sample into an oil phase sample pipeline through an oil phase injector;
and respectively connecting the water phase injector and the oil phase injector through a droplet generation module to generate micro droplets.
9. The method of claim 8, further comprising, before the sucking the plurality of sections of the aqueous phase sample and the oil phase sample into the aqueous phase sample pipeline by the aqueous phase injector:
injecting an oil phase sample into the water phase injector and the oil phase injector, and discharging air inside the water phase injector and the oil phase injector.
10. The method of claim 8, wherein the sucking the multiple sections of the aqueous phase sample and the oil phase sample into the aqueous phase sample pipeline by the aqueous phase injector comprises:
the water phase sample is subjected to the dominant action of capillary force in the water phase sample pipeline and is stored in the water phase sample pipeline in a liquid section mode.
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| CN113533033A (en) * | 2021-07-19 | 2021-10-22 | 长春工程学院 | Metal wire Young modulus measuring instrument based on hydraulic pressure micro displacement amplifier principle |
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