CN108339578A - Drop injector and use its drop sample injection method - Google Patents
Drop injector and use its drop sample injection method Download PDFInfo
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- CN108339578A CN108339578A CN201710060887.7A CN201710060887A CN108339578A CN 108339578 A CN108339578 A CN 108339578A CN 201710060887 A CN201710060887 A CN 201710060887A CN 108339578 A CN108339578 A CN 108339578A
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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
- B01L3/502769—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 multiphase flow arrangements
- B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
-
- 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
- B01L2200/12—Specific details about manufacturing devices
-
- 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
- B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
Abstract
The present invention relates to a kind of drop injector and use its drop sample injection method.The drop injector is the drop injector for microfluidic control field, micro liquid sample can be transferred to closed microchannel system by it from open system, and micro liquid sample is packed in Medium Oil especially in the form of Water-In-Oil and is transported in microchannel system.The drop injector includes sample channel, is used to suck and convey fluid sample, which connect with the module for providing negative pressure；Medium channel is used to push medium, which connect with the module for providing positive pressure；Sample channel and medium channel are in fluid communication.
Description
Technical field
The present invention relates to a kind of drop injector and its drop sample injection method is used, in particular for micro-fluidic field
Drop injector, micro liquid sample can be transferred to closed microchannel system from open system, especially be situated between
Micro liquid sample is packed in medium, such as oil droplet and in microchannel system by matter packet fluid sample, such as the form of Water-In-Oil
Middle transport.
Background technology
Microfluidic chip technology be widely applied to sample preparation during biology, chemistry, medical analysis etc., reaction,
It is the cutting edge technology of the rapid development field one of the most active with research in the work such as separation, detection.To the behaviour of fluid sample
Work is very important in fields such as chemistry, microorganism, biochemistry, molecular biology, medical analysis.Fluid sample for example may be used
To be the various lifes of cell culture fluid, cell effect liquid, protein solution, DNA solution, RNA solution, different culture mediums etc.
Common fluid sample in the fields such as object, chemistry, medical analysis.
With the continuous development of microfluidic chip technology, plurality of liquid sample is shifted into microchannel system from open system
Demand gradually highlight, and largely constrain the application development of the technology.Common open system in the art,
Such as having the various systems reacted in 96 orifice plates, centrifuge tube, flask, sample cell etc., microchannel system is such as microlayer model core
Piece, capillary, microreactor etc..
Invention content
The application for a patent for invention of CN102426261A discloses a kind of micro-fluidic chip Multi-example sequence recording device, the dress
Set including sample memotron and two-way pump, one end setting sample of the sample memotron is imported and exported, the other end be arranged sample into
Go out control mouth, the two-way pump is connected to sample disengaging control mouth, and Multi-example sequence load is carried out using above-mentioned loading device
Method is：Reverse the negative pressure generated that various samples are sucked sample storage successively by the reverse order of Loading sequence by two-way pump
Pipe, sucking separation gas is isolated after often sucking a kind of sample, due to carrying out the isolation of Multi-example progress using air, is passed through
Two-way pump rotates forward the sequence load that Multi-example can be realized in the positive pressure generated.
The application for a patent for invention of CN102740975A discloses a kind of dress for fluid to be mixed and delivered in miniflow system
It sets and method, the device being directed to includes：Entrance, outlet, the upstream passageway part being in fluid communication with entrance, with outlet fluid
The downstream passage part of connection, the drain valve being arranged between upstream passageway part and downstream passage part, and it is stored in upstream
First fluid at least one of channel part and downstream passage part, the wherein device be seal and be constructed and
It is arranged for that first fluid is stored at least one hour in device before first use.This method includes providing a kind of dress
It sets, which includes：Main channel；Accommodate the first branched bottom of first fluid；The second branched bottom of second fluid is accommodated,
Described in the first branched bottom and the second branched bottom connected in infall and be fluidly coupled to main channel, and be arranged in first
Drain valve between a part for branched bottom and a part for main channel；Actuated drain valve；Make first fluid and second fluid
Infall is substantially simultaneously flowed into, and at least partly first fluid and second fluid is made to mix to generate fluid-mixing.The invention
Patent application is by using one or more drain valves with the fluid section in controllable flow and/or mixing microfluidic system.
CN103454126A applications for a patent for invention disclose a kind of adjustable liquid droplet generating means based on capillary.The hair
Generating apparatus can drive generation nanoliter to the drop of picoliters magnitude by positive pressure or negative pressure.The generating means includes T-type three-way connection
1, reducer pipe 2, dispersed phase input terminal 3, continuous phase flow into the straight tube of end 4 and suspending drops liquid stream outlet 5, T-type three-way connection 1
It is connected with 2 larger interior diameter end of reducer pipe, capillary one end, that is, tip is drawn and attenuated to 2-50 microns and as dispersed phase input terminal 3
It is inserted into reducer pipe 2 across the straight tube of T-type three-way connection 1, the branch pipe of T-type three-way connection 1 is that continuous phase flows into end 4；Simultaneously
Capillary is inserted into 2 smaller inner-diameter end of reducer pipe as suspending drops liquid stream outlet 5 and is connected；Dispersed phase and continuous phase pass through
Positive pressure or negative pressure driving；Dispersed phase rushes across the straight tube of T-type three-port structure 1 by dispersed phase input terminal 3 and enters reducer pipe 2, quilt
The continuous phase flowed by continuous phase input terminal 4 is divided into one group of drop and is suspended in continuous phase, and drop is successively through 2 He of reducer pipe
Suspending drops liquid stream outlet 5 flows out.
U.S. Patent application US20140147908A1 discloses the method cut to drop using negative pressure.
Above- mentioned information is used only for enhancing the understanding to background of the present invention, it is thus possible to common comprising this field is not formed in
The information of the prior art well known to technical staff.Above-mentioned patent application text relates to use positive pressure or negative pressure, is taken to realize
Sample either conveys or by realizing cutting and sampling to drop in the pipeline that crosses.
But above-mentioned patent application and the prior art are not directed to realize using positive/negative-pressure alternate samples, push,
And it realizes sample drop is carried out after medium (being usually oil) package fluid sample (forming so-called water in oil form) simultaneously
The device and method of cutting.Simultaneously the device also guarantee will extra sample exit conduit, barrier sample and sample between
Pollution.
In addition, drop injector in the prior art also cannot achieve the sample introduction of a variety of different samples, due to micro-fluidic
Chip field can be realized simultaneously the detection of various samples, such as common high flux screening etc. using micro-fluidic chip.Usually
A large amount of mutant is screened simultaneously for certain mutation system, so if it is different that a drop injector can be utilized to obtain
Fluid sample, and be seriatim detected into chip, the workload of screening operation will be greatlyd save.Simultaneously because sample introduction
Fluid sample is typically the effect system of cell culture fluid, tissue reaction's liquid, protein or enzyme, therefore in the multiple liquid-likes of sample introduction
Also wanting to realize while product effectively to be coated and be obstructed to each sample, to prevent the pollution between sample.
And in the prior art without reference to such device, it may be implemented for different reaction systems, cultivating system
The sampling that the sample of the equal different system in sources does not pollute continuously, each other, and realize will be taken using medium simultaneously
The sample obtained is wrapped up and is cut.
Based on the needs in above-mentioned problems of the prior art and micro-fluidic field, the purpose of the present invention is to provide
A kind of drop injector can be by micro liquid sample from open body in particular for the drop injector in micro-fluidic field
System is transferred to closed microchannel system, especially with medium packet fluid sample, such as Water-In-Oil form by micro liquid sample
Product are packed in medium, such as oil droplet and are transported in microchannel system.
It is another object of the present invention to provide a kind of method of sample introduction micro liquid sample, by using this method,
Micro liquid sample can be transferred to closed microchannel system from open system, especially with medium packet fluid sample, example
As micro liquid sample is packed in medium, such as oil droplet by the form of Water-In-Oil and is transported in microchannel system.
Using the method for the drop injector and sample introduction micro liquid sample of the present invention, may be implemented to replace using positive/negative-pressure
Sampling, push, and realize after medium (being usually oil) package fluid sample (forming so-called water in oil form) to sample liquid
Drip the device and method cut.The device also guarantees, by extra sample exit conduit, to obstruct sample introduction twice simultaneously
Sample and sample between pollution.
Using the method for the drop injector and sample introduction micro liquid sample of the present invention, may be implemented for different reactions
The sampling that the fluid sample of the different system in the sources such as system, cultivating system does not pollute continuously, each other, and it is real simultaneously
Now acquired sample is wrapped up and cut using medium.
The purpose of the present invention is be achieved by the following technical programs.
1. a kind of drop injector comprising：
Sample channel is used to suck and convey fluid sample, which connect with the module for providing negative pressure；
Medium channel is used to push medium, which connect with the module for providing positive pressure；
Sample channel and medium channel are in fluid communication.
2. the drop injector according to item 1, wherein the internal diameter of sample channel be 10 microns~5 millimeters, preferably 50
Micron~2 millimeters, further preferably 100 microns~1 millimeter, further preferably 200 microns~0.6 millimeter.
3. the drop injector according to item 1 or 2, wherein the internal diameter of medium channel is 5 microns~10 millimeters, preferably
It is 25 microns~4 millimeters, further preferably 50 microns~2 millimeters, further preferably 100 microns~1.2 millimeters.
4. the drop injector according to any one of item 1~3, wherein the internal diameter of sample channel and medium channel it
Than ranging from the 1 of (sample channel internal diameter/medium channel internal diameter):10~10:1, preferably 1:5~5:1, further preferably 1:
2~2:1, or 1:1.
5. the drop injector according to any one of item 1~4, wherein the sample channel and medium channel by
Hydrophobic material is formed or inside is coated through hydrophobic material.
6. the drop injector according to any one of item 1~5, wherein the sample channel and medium channel are direct
Connection.
7. the drop injector according to any one of item 1~6, wherein the sample channel passes through with medium channel
Common container, which is realized, to be in fluid communication.
8. the drop injector according to any one of item 1~7, wherein provide the module of negative pressure and provide positive pressure
Module is plunger pump.
9. the drop injector according to any one of item 1~8, wherein medium is hydrophobic, and fluid sample is parent
Aqueous.
10. the drop injector according to any one of item 1~9, wherein drop injector makes before beginning to use
Medium is full of in its sample channel and medium channel.
11. a kind of method of sample introduction micro liquid sample comprising using drop injector, which includes：
Sample channel is used to suck and convey fluid sample, which connect with the module for providing negative pressure；
Medium channel is used to push medium, which connect with the module for providing positive pressure；
Sample channel and medium channel are in fluid communication,
The method includes：
The first step：It is closing the module that negative pressure is provided and the module that positive pressure is provided and is being filled in sample channel, medium channel
Under the premise of full medium, drop injector is inserted into fluid sample to be taken,
Second step：The module absorption fluid sample for opening offer negative pressure enters sample channel.
Third walks：It closes the module that negative pressure is provided and opens the module that positive pressure is provided, be situated between to be released from medium channel
The fluid sample that matter makes medium be sucked with second step contacts, and makes to retain a certain amount of fluid sample in sample channel, and to
Make a certain amount of fluid sample retained in sample channel by media packs.
4th step：It closes the module for positive pressure and remains turned-off the module that negative pressure is provided, stop push-in medium, to complete
The sample introduction of sample,
The step of repeating the first step~four step, to complete new primary sample feeding.
12. according to the method described in item 11, wherein a sample and the new primary sample are different liquid
Sample.
13. the method according to item 11 or 12, wherein the drop injector is according to any one of item 1~10 institute
The drop injector stated.
14. the method according to item 11 or 12, wherein in second step, the module for opening offer negative pressure is drawn excessively
The fluid sample position that enters sample channel and its overwrite media channel is made directly to be connected to sample channel.
In the third step：It closes the module that negative pressure is provided and opens the module that positive pressure is provided, to be pushed away from medium channel
Go out the fluid sample that medium makes medium suck with second step to contact, and fluid sample extra in sample channel is led to from sample
It is released in road, makes to retain a certain amount of fluid sample in sample channel, and a certain amount of to make to retain in sample channel
Fluid sample is by media packs.
15. the method according to item 11 or 12, wherein in second step, open the module absorption liquid for providing negative pressure
Sample enters sample channel,
In the third step：It closes the module that negative pressure is provided and opens the module that positive pressure is provided, to be pushed away from medium channel
Go out the fluid sample that medium makes medium suck with second step to contact, and will be outside the fluid sample and sample channel in sample channel
The fluid sample in portion detaches, and makes to retain a certain amount of fluid sample in sample channel, and to make to retain in sample channel
A certain amount of fluid sample is by media packs.
As described above, the structure of the drop injector of embodiments of the present invention is simple, supplied by the alternating of positive and negative pressure
To sample introduction, cutting, medium package and the separation for realizing droplet sample.The drop injector is without using usually used in the prior art
Valve etc., therefore its is simple in structure.In addition, the drop injector of the present invention may be implemented to each sample into sample channel
Wrapped up, cut and is discharged extra sample, so as to so that every time sample introduction sample be isolated from each other not mutually pollution with
It influences, therefore may be implemented to various samples continuous sample introduction.
Above description is only the general introduction of technical solution of the present invention, in order to make the technological means of the present invention clearer
Understand, reach the degree that those skilled in the art can be implemented in accordance with the contents of the specification, and in order to allow the present invention
Above and other objects, features and advantages can be clearer and more comprehensible, below with the present invention specific implementation mode illustrate
Explanation.
Description of the drawings
By reading the detailed description in hereafter preferred embodiment, the present invention various other advantage and benefit
Those of ordinary skill in the art will become clear.Figure of description only for the purpose of illustrating preferred embodiments,
And it is not considered as limitation of the present invention.It should be evident that drawings discussed below is only some embodiments of the present invention,
For those of ordinary skill in the art, without creative efforts, it can also be obtained according to these attached drawings
Other attached drawings.And throughout the drawings, identical component is presented with like reference characters.
The schematic diagram of Fig. 1 drop injectors of the present invention.
The flow diagram that Fig. 2 (a) drop injectors of the present invention wrap up drop using medium and cut, pushed, Fig. 2
(b) operating process of the processing sample of drop injector of the present invention is utilized.
Two kinds of modes of texturing of Fig. 3 (a) and (b) drop injector of the present invention.
The drop injector of the present invention is used for the ideograph of micro-fluidic sampler by Fig. 4.
Specific implementation mode
Specific embodiments of the present invention are more fully described below with reference to accompanying drawings.Although showing the present invention's in attached drawing
Specific embodiment, it being understood, however, that may be realized in various forms the present invention without should be limited by embodiments set forth here
System.It is to be able to be best understood from the present invention on the contrary, providing these embodiments, and can be complete by the scope of the present invention
Be communicated to those skilled in the art.
Fig. 1 gives the schematic diagram of drop injector of the present invention.Fig. 1 schematically shows sample channel and medium channel
Correlativity.From figure 1 it appears that the drop injector of the present invention includes：Sample channel is used to suck and conveys liquid
Body sample, the sample channel are connect with the module for providing negative pressure；Medium channel is used to push medium, the medium channel with carry
For the module connection of positive pressure, sample channel and medium channel are in fluid communication.
The sample channel provided in schematic diagram in Fig. 1 is directly connected to medium channel, and those skilled in the art can
To understand that Fig. 1 is only schematical, the mode of communicating of sample channel and medium channel is not limited to mode shown in Fig. 1.Sample
The mode of communicating of product channel and medium channel is to be in fluid communication, i.e., fluid can enter medium channel, Yi Jicong from sample channel
Medium channel enters sample channel.Hereinafter, the present invention also provides fluids between several realization sample channel and medium channels
The mode of texturing of connection.It will be appreciated by those skilled in the art that any can realize that the mode of fluid communication is included in the present invention
Range in.
Sample channel and medium channel as shown in Figure 1 are connect with the module for providing negative pressure and the module for providing positive pressure respectively.
In the present invention, it is not particularly limited for providing negative pressure and providing the module of positive pressure, known to any those skilled in the art
Mode may be implemented, for example, can enumerate the promotion realized for example, by the mode of needle tubing and suction with provide respectively positive pressure and
Negative pressure can also enumerate the pump for being capable of providing positive pressure and negative pressure, due to being used in micro-fluidic field, drop sample introduction of the invention
It is preferable to use the equipment such as plunger pump, syringe pump for device；Medium can also be pushed by positive/negative-pressure gas source to provide；Or it is any can be with
Realize the other modes of identical function.
In addition, the working time of positive/negative-pressure can be controlled by the switch of solenoid valve, so as to realize specified
Time automation continuous sample introduction.
As shown in Fig. 2 (a) and (b), flow when giving the drop feeder fluid sample using the present invention is shown
It is intended to.As shown in Fig. 2 (a), before 1- aspiration steps, it is full of by medium in the medium channel and sample channel of drop injector,
In 1- aspiration steps, the module that negative pressure is provided is opened, excessive fluid sample is drawn into sample channel by negative pressure, and
And so that the fluid sample and medium channel is in fluid communication, as the upper lefts Fig. 2 (a) figure in arrow shown in, in the signal of Fig. 2 (a)
In the case of shown in figure, which directly contacts with medium channel, covers medium channel and is contacted with sample channel
Outlet.It in 2- cuts (separation) step, is first shut off the module that negative pressure is provided and opens the module that positive pressure is provided, at this time will
Medium in medium channel is proposed and is contacted with excessive fluid sample, is cut to the fluid sample and (sample is divided into two
Part), and extra sample is released from sample channel, as Fig. 2 (a) upper rights figure in arrow shown in.It is released in 3-
In step, sustainable supply positive pressure all releases extra sample from sample channel, retains in sample channel to realize
Fluid sample by media packs (can also become package), be then shut off the module that positive pressure is provided and offer negative pressure be provided
Module, so as to complete the sample introduction of a sample, as the bottom rights Fig. 2 (a) figure in arrow shown in.In the step of 4- is drawn again
In, be again turned on the module that negative pressure is provided, suck new sample, and by previous step step by media packs or package
Sample pushes forward.As described above, the step in sample injection method of the invention is repeated again, to realize the sample introduction mistake of new sample
Journey.
Above-mentioned whole process is shown further in Fig. 2 (b), and sample appearance is also schematically shown in Fig. 2 (b)
Device, wherein being put into fluid sample to be taken.
The method of the sample introduction micro liquid sample of the present invention includes the following steps as described above：
The first step：It is closing the module that negative pressure is provided and the module that positive pressure is provided and is being filled in sample channel, medium channel
Under the premise of full medium, drop injector is inserted into fluid sample to be taken (as shown in the figure of the leftmost side in Fig. 2 (b)),
Second step：Open provide negative pressure module draw fluid sample enter sample channel (in such as Fig. 2 (b) from left side
Shown in the second figure of number),
Third walks：It closes the module that negative pressure is provided and opens the module that positive pressure is provided, be situated between to be released from medium channel
The fluid sample that matter makes medium be sucked with second step contacts, and makes to retain a certain amount of fluid sample in sample channel, and to
Make a certain amount of fluid sample retained in sample channel by media packs (as shown in figure intermediate Fig. 2 (b)),
4th step：It closes the module for positive pressure and remains turned-off the module that negative pressure is provided, stop push-in medium, to complete
The sample introduction (on the right side of Fig. 2 (b) shown in the second figure) of sample,
The step of repeating the first step~four step, to complete new primary sample feeding (such as figure of the rightmost sides Fig. 2 (b)
It is shown).
In the above-mentioned methods, a certain amount of fluid sample refer to by the amount of the sample used in follow-up microchannel system,
For example, being the sample size for waiting for being detected by the detector on the chip in microchannel system, or need in microchannel
Sample size to be treated in system, or it is drawn into the other samples for being used for and waiting in microchannel system with microchannel system
The sample size that product are contacted or reacted.
For this it is a certain amount of do not limit specifically, skilled person will know how according to the processing of subsequent sample or
It detects to select amount appropriate, such as can enumerate：1 nanoliter~20 microlitres, 2 nanoliters~15 microlitres, 5 nanoliters~10 microlitres, 10
Nanoliter~9 microlitres, 50 nanoliters~5 microlitres etc., can be specifically such as 20 microlitres, 15 microlitres, 10 microlitres, 9 microlitres, 8 microlitres,
7 microlitres, 6 microlitres, 5 microlitres, 4 microlitres, 3 microlitres, 2 microlitres, 1.5 microlitres, 1 microlitre, 900 nanoliters, 800 nanoliters, 700 nanoliters, 600
Nanoliter, 500 nanoliters, 400 nanoliters, 300 nanoliters, 200 nanoliters, 100 nanoliters, 50 nanoliters, 30 nanoliters, 10 nanoliters, 5 nanoliters, 1 nanoliter
Etc..
According to foregoing description it is recognised that using drop injector of the invention, fluid sample can be effectively realized
Sample introduction, and fluid sample is cut using medium and releases extra fluid sample and (sample is divided into two parts simultaneously
Retain a certain amount of sample subsequently used, or the sample near sample channel is divided with a certain amount of sample subsequently used
From), it then realizes and is wrapped up remaining fluid sample to be operated using medium, thus complete primary sample feeding.Pass through this
The device and method of sample, can the continuously different fluid sample of sample introduction, and can be isolated from each other between each fluid sample
It does not interfere with each other.
After completing the work of a primary or stage sample introduction, input end is closed, outlet end is opened, positive pressure expulsion can be passed through
Adjust position of the sample drop in microchannel system；It, can be by continuing if connecting another microchannel system in outlet end
Sample drop is transferred in the system by positive pressure expulsion.
In addition, the inducer of sample channel can be closed when without sample introduction, mode is closed, can be used but unlimited
In mode one：The cap is buckled on input end and closes that is, using the cap that can be sleeved on input end by shell type；Mode two：
Pressure type, make it is soft, such as rubber pad, and press on input end with realizes closing.
Flow when Fig. 1 and Fig. 2 is only structure and its operation for schematically illustrating the drop injector of the present invention
Schematic diagram.Container in Fig. 2 (b) for holding sample can be the open system in the present invention as described above, such as 96 orifice plates,
The various forms such as centrifuge tube, flask, sample cell.The fluid sample can also be the sample of the various liquid forms in this field
Product, such as the aqueous solution of chemical reagent, cell culture fluid, cell effect liquid, enzyme reaction solution, protein solution, DNA, RNA etc. are each
The solution etc. of kind picodna or nucleic acid.
In the drop injector of the present invention, do not have for the size of its drop injector specifically defined, preferably helps
In the size for realizing medium package fluid sample.Such as the internal diameter of sample channel be 10 microns~5 millimeters, preferably 50 microns~
2 millimeters, further preferably 100 microns~1 millimeter, further preferably 200 microns~0.6 millimeter.Such as sample channel
Internal diameter can be 10 microns, 20 microns, 30 microns, 40 microns, 50 microns, 60 microns, 70 microns, 80 microns, 90 microns, 100
Micron, 200 microns, 300 microns, 400 microns, 500 microns, 600 microns, 700 microns, 800 microns, 900 microns, 1 millimeter,
1.5 millimeters, 2 millimeters, 3 millimeters, 4 millimeters, 5 millimeters.The above concrete numerical value is only to enumerate, and can be in 10 microns~5 millimeters
Arbitrary specific numerical value.
Such as the internal diameter of medium channel is 5 microns~10 millimeters, preferably 25 microns~4 millimeters, further preferably 50
Micron~2 millimeters, further preferably 100 microns~1.2 millimeters.Such as the internal diameter of medium channel can be 5 microns, 6 microns,
7 microns, 8 microns, 9 microns, 10 microns, 20 microns, 30 microns, 40 microns, 50 microns, 60 microns, 70 microns, 80 microns, 90
Micron, 100 microns, 200 microns, 300 microns, 400 microns, 500 microns, 600 microns, 700 microns, 800 microns, 900 microns,
1 millimeter, 1.5 millimeters, 2 millimeters, 3 millimeters, 4 millimeters, 5 millimeters, 6 millimeters, 7 millimeters, 8 millimeters, 9 millimeters, 10 millimeters.It is above specific
Numerical value is only to enumerate, and can be the arbitrary specific numerical value in 5 microns~10 millimeters.
Further, the relationship of the internal diameter between sample channel and medium channel is not limited specifically, as long as having
Help realize the ratio between the ratio, such as the internal diameter of sample channel and medium channel of medium package fluid sample (sample channel
Internal diameter/medium channel internal diameter) ranging from 1:10~10:1, preferably 1:5~5:1, further preferably 1:2~2:1, it can be with
For for example, 1:1.
Above, the signified internal diameter of the present invention is medium channel or the diameter of sample channel inner passage.
In the present invention, as described above, fluid sample can be chemical reagent aqueous solution, cell culture fluid, cell it is anti-
Answer the solution etc. of the various picodnas such as liquid, enzyme reaction solution, protein solution, DNA, RNA or nucleic acid, liquid in the present invention
Body sample is preferably hydrophilic or aqueous sample.
The medium being used in the present invention is typically lipophilic medium, can be used usually used in this field various
Oily substance.Such as mineral oil, low temperature paraffin, vegetable oil.
In the present invention, what the material of drop injector is limited without, as long as can be achieved on through the invention
Operation may be implemented medium package fluid sample material.It is preferred that sample channel and medium channel are by hydrophobic material shape
At or its inside coat through hydrophobic material.Hydrophobic material enumerate polytetrafluoroethylene (PTFE) (PTFE), polymethyl methacrylate (PMMA),
Polyethylene (PE), polypropylene (PP), polystyrene (PS) etc. have hydrophobic high-molecular organic material, can also be stainless
The metal materials such as steel, titanium alloy, copper, platinum, gold.
In a specific embodiment of drop injector of the present invention, sample channel is straight with medium channel
Lead in succession.The direct connection realized by threeway mode shown in Fig. 2 (a) is specifically may refer to, medium is utilized to work as
Come when cutting fluid sample, the medium released using positive pressure can directly be contacted with the excessive fluid sample of sucking and to its into
Row cutting, and extra fluid sample is further released, package is desirably used for the sample of subsequent operation or detection.
In the method using the sample introduction micro liquid sample of the specific implementation mode, in second step, opens to provide and bear
The module of pressure draws excessive fluid sample and enters sample channel and its overwrite media channel is made directly to be connected to sample channel
Position (fluid sample is directly contacted with medium channel, covers the outlet that medium channel is contacted with sample channel),
In three steps：It closes the module that negative pressure is provided and opens the module that positive pressure is provided, make medium to release medium from medium channel
It is contacted with the fluid sample of second step sucking, and fluid sample extra in sample channel is released from sample channel, made
Retain a certain amount of fluid sample in sample channel, and to make a certain amount of fluid sample retained in sample channel be situated between
Matter coats.
In another specific embodiment of drop injector of the present invention, sample channel and medium channel
It is realized and is in fluid communication by common container.It specifically may refer to two kinds of illustrative embodiment party that Fig. 3 (a) and (b) are provided
Formula.
In the method using the sample introduction micro liquid sample of the specific implementation mode, in second step, opens to provide and bear
The module of pressure draws fluid sample and enters sample channel, in the third step：It closes the module that negative pressure is provided and offer positive pressure is provided
Module, contact and (such as lead in sample to release the medium fluid sample that makes medium be sucked with second step from medium channel
Road junction is contacted, such as shown in Fig. 3 (a) and 3 (b)), and will be outside the fluid sample and sample channel in sample channel
Fluid sample (such as near sample channel mouth or the fluid sample that is attached to outside sample channel) separation, makes in sample channel
Retain a certain amount of fluid sample, and to make a certain amount of fluid sample retained in sample channel by media packs.
Specifically, in Fig. 3 (a), the internal diameter of sample channel is less than the internal diameter of medium channel, and medium channel is logical with sample
The form of road packaged tube, i.e. medium channel are located at the outside of sample channel, at this time can be by underlying full of medium
Container realizes that medium channel and sample channel are to be in fluid communication.As shown in Fig. 3 (a), it is situated between by the way that the container of lower section to be full of
Matter, and by the entrance of medium channel and sample channel be inserted into this full of medium container in, you can with realize medium channel with
Sample channel is to be in fluid communication.
As a result, utilize the liquid sample feeding device realize sample introduction when, first in the first step, close provide negative pressure module and
There is provided in the module of positive pressure and sample channel, medium channel full of under the premise of medium, by drop shown in Fig. 3 (a) into
Sample device is inserted into fluid sample to be taken, be at this time will be filled with medium the related medium channel of container and sample channel be inserted into together
Into fluid sample to be taken.Second step, the module absorption fluid sample for opening offer negative pressure pass through the container full of medium to enter
Sample channel, at this time the end of fluid sample be located at the entrance of sample channel, can be contacted with medium fluid.It is walked in third
In：It closes and the module of negative pressure is provided simultaneously opens the module that positive pressure is provided, make medium and the to release medium from medium channel
The fluid sample (mainly sample is located at the end of sample channel import) of two steps sucking contacts, and by the liquid in sample channel
Body sample is detached with the fluid sample outside sample channel, makes to retain a certain amount of fluid sample in sample channel, and to
Make a certain amount of fluid sample retained in sample channel by media packs.In the present embodiment, the liquid outside sample channel
Body sample be typically situated on the outside of the entrance of sample channel and near, or the sample outside sample channel.Most
4th step afterwards closes the module for positive pressure and remains turned-off the module for providing negative pressure, stop push-in medium, to complete a sample
The sample introduction of product.The step of repeating the first step~four step, to complete new primary sample feeding.
In the specific embodiment shown in above-mentioned Fig. 3 (a), the container full of medium can be the rifle of such as liquid-transfering gun
The container or syringe needle of first-class taper can also be any other similar container, as long as can be by itself and sample
When channel and medium channel are inserted into fluid sample together, it can realize that fluid sample is drawn into sample by the container to be led to
Container in road.
In addition, as described above, the container equipped with fluid sample can be that 96 orifice plates, test tube, flask, culture dish etc. are various
Open system.In addition, in the embodiment provided in Fig. 3 (a), the internal diameter of medium channel is more than the internal diameter of sample channel, this
Field technology personnel are appreciated that by the way of opposite, that is, the internal diameter of medium channel is less than the internal diameter of sample channel, and medium is logical
Road is located at what the embodiment of the inside of sample channel also can be achieved on, if may be implemented aforementioned present invention it is described into
The method of sample micro liquid sample.In the present invention, it is preferred to the internal diameter of medium channel is more than the internal diameter of sample channel, to
The cutting to redundant sample can be better achieved.
Further, as shown in Fig. 3 (a), sample channel is reached into sample port outside medium channel, art technology
Personnel it is also to be understood that at this time sample channel with the medium entrance of medium channel can be into sample port it is parallel, can also
It it is being located in medium channel into sample port for sample channel, as long as sample introduction micro liquid described in aforementioned present invention may be implemented
The method of sample.In the present invention, it is preferred to which the length of sample channel is longer than the length of medium channel, so as to preferably
Realize the cutting to redundant sample.
In addition, Fig. 3 (b) also shows another form in present embodiment, i.e. sample channel and medium channel is not
It is realized in the form of casing, but in addition to this two channels arranged side by side are consistent with form shown in Fig. 3 (a).This
When the sample present invention described in sample introduction micro liquid sample method.The internal diameter of channel and medium channel can be identical, also may be used
With difference, as long as the method that can realize sample introduction micro liquid sample described in aforementioned present invention.In addition, sample channel
With the medium entrance of medium channel can be parallel into sample port, can also be not parallel, as long as can realize above-mentioned
The method of sample introduction micro liquid sample described in the invention.In the present invention, it is preferred to which the length of sample channel is longer than Jie
The length in matter channel, so as to which the cutting to redundant sample is better achieved.
When the drop injector of the present invention is used for micro-fluidic field, the schematic diagram of operation is as shown in Figure 4.The first step
Under the premise of closing the module that negative pressure is provided and the module that positive pressure is provided and being full of medium in sample channel, medium channel,
Drop injector is inserted into fluid sample to be taken, then in second step, opens the module absorption liquid-like that negative pressure is provided
Product enter sample channel, then in the third step, close the module for providing negative pressure and open the module for providing positive pressure, thus from Jie
The fluid sample that medium makes medium suck with second step is released in matter channel to contact, and makes to retain a certain amount of liquid in sample channel
Sample, and to make a certain amount of fluid sample retained in sample channel by media packs, then in the 4th step, close
It closes the module for positive pressure and remains turned-off the module that negative pressure is provided, stop push-in medium, to complete the sample introduction of a sample.
Then, the step of repeating the first step~four step, to complete new primary sample feeding.
By media packs and the fluid sample of sucking as rear single injected sampling is gradually pushed ahead, and it is advanced to microchannel
For subsequent detection and processing in system, and can be discharged from sample export after detection finishes.Pass through weight as a result,
Positive pressure, negative pressure module are closed in strike-on open and close, and that realizes sample enters package, and enters in microchannel system and be detected.
In addition, also depicting closing cap in Fig. 4, sample inlet can be closed when being not used in sample introduction, to
Prevent the pollution of sample channel.In addition, after fluid sample completes detection or processing, need to be shifted or discarded drop
When, it needs to cover closing cap, then opens positive pressure again and release or shift droplet sample, i.e., arrange droplet sample from whole system
It removes.
In addition, the drop injector of the present invention can be sampled for different samples, in first time sample introduction fluid sample
After, it can be clean by the pipeline cleaning near sample inlet by the methods of wiping, rinsing, then in second sample introduction
When the drop injector can be inserted into addition different sample liquids and be sampled, such as 96 orifice plates, or
Multi-example system can utilize a drop injector to enter different samples simultaneously, to simply implement many body system sample
Detection, and enter the sample in sample channel due to that by dielectric distance, will not transport each other
It pollutes and influences each other during in microchannel system.
The schematic diagram that drop injector of the invention is combined in whole system is only schematically depicted in Fig. 4,
It will be understood by those skilled in the art that the specific implementation mode of all drop injectors of the present invention can be combined to miniflow
Control system, for droplet sample to be sent in microchannel system.
In the present invention, microchannel system can be micro-fluidic chip, and the sample for transporting microchannel system can be micro-
It is handled and is detected in fluidic chip.In addition, microchannel system further include those skilled in the art will know that other be used for miniflow
The pipeline system of control field, such as capillary etc..
The application receives various modifications and interchangeable form, and specific embodiment is in the accompanying drawings by means of implementing
Example come show and the application be described in detail.But the application is not intended to be limited to disclosed particular form.On the contrary,
The application is intended to include all modifications form, equivalent and the refill within the scope of the application, and scope of the present application is by appended
Claim and its legal equivalents limit.
The numberical range enumerated in the present invention includes the data of two endpoints of the numberical range, also includes the numerical value
Each specific numerical value in range, and the numerical value can with endpoint arbitrary group be combined into new small range.
Claims (13)
1. a kind of drop injector comprising：
Sample channel is used to suck and convey fluid sample, which connect with the module for providing negative pressure；
Medium channel is used to push medium, which connect with the module for providing positive pressure；
Sample channel and medium channel are in fluid communication.
2. drop injector according to claim 1, wherein the internal diameter of sample channel is 10 microns~5 millimeters, preferably
50 microns~2 millimeters, further preferably 100 microns~1 millimeter, further preferably 200 microns~0.6 millimeter.
3. drop injector according to claim 1 or 2, wherein the internal diameter of medium channel is 5 microns~10 millimeters, excellent
It is selected as 25 microns~4 millimeters, further preferably 50 microns~2 millimeters, further preferably 100 microns~1.2 millimeters.
4. drop injector described in any one of claim 1 to 3, wherein the internal diameter of sample channel and medium channel
The ratio between (sample channel internal diameter/medium channel internal diameter) ranging from 1:10~10:1, preferably 1:5~5:1, further preferably
1:2~2:1.
5. drop injector according to any one of claims 1 to 4, wherein the sample channel and medium channel
It is formed by hydrophobic material or inside is coated through hydrophobic material.
6. drop injector according to any one of claims 1 to 5, wherein the sample channel and medium channel are straight
Lead in succession.
7. according to drop injector according to any one of claims 1 to 6, wherein the sample channel is logical with medium channel
It crosses common container and realizes and be in fluid communication.
8. drop injector according to any one of claims 1 to 7, wherein medium is hydrophobic, and fluid sample is
It is hydrophilic.
9. a kind of method of sample introduction micro liquid sample comprising using drop injector, which includes：
Sample channel is used to suck and convey fluid sample, which connect with the module for providing negative pressure；
Medium channel is used to push medium, which connect with the module for providing positive pressure；
Sample channel and medium channel are in fluid communication,
The method includes：
The first step：It is situated between closing the module for providing negative pressure and the module for providing positive pressure and being full of in sample channel, medium channel
Under the premise of matter, drop injector is inserted into fluid sample to be taken,
Second step：The module absorption fluid sample for opening offer negative pressure enters sample channel,
Third walks：It closes the module that negative pressure is provided and opens the module that positive pressure is provided, make to release medium from medium channel
Medium is contacted with the fluid sample that second step sucks, and makes to retain a certain amount of fluid sample in sample channel, and to make sample
A certain amount of fluid sample retained in product channel by media packs,
4th step：It closes the module for positive pressure and remains turned-off the module that negative pressure is provided, stop push-in medium, it is primary to complete
The sample introduction of sample,
The step of repeating the first step~four step, to complete new primary sample feeding.
10. according to the method described in claim 9, wherein, a sample and the new primary sample are different liquid
Body sample.
11. method according to claim 9 or 10, wherein the drop injector is appointed according in claim 1~8
Drop injector described in one.
12. method according to claim 9 or 10, wherein in second step, the module for opening offer negative pressure is drawn excessively
The fluid sample position that enters sample channel and its overwrite media channel is made directly to be connected to sample channel.
In the third step：It closes the module that negative pressure is provided and opens the module that positive pressure is provided, be situated between to be released from medium channel
The fluid sample that matter makes medium be sucked with second step contacts, and by fluid sample extra in sample channel from sample channel
It releases, makes to retain a certain amount of fluid sample in sample channel, and to make a certain amount of liquid retained in sample channel
Sample is by media packs.
13. method according to claim 9 or 10, wherein in second step, open the module absorption liquid for providing negative pressure
Sample enters sample channel,
In the third step：It closes the module that negative pressure is provided and opens the module that positive pressure is provided, be situated between to be released from medium channel
The fluid sample that matter makes medium be sucked with second step contacts, and will be outside the fluid sample and sample channel in sample channel
Fluid sample detaches, and makes to retain a certain amount of fluid sample in sample channel, and certain to make to retain in sample channel
The fluid sample of amount is by media packs.
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| CN201710060887.7A CN108339578B (en) | 2017-01-25 | 2017-01-25 | Droplet injector and droplet injection method using the same |
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| CN201710060887.7A CN108339578B (en) | 2017-01-25 | 2017-01-25 | Droplet injector and droplet injection method using the same |
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