CN113092796A - Accurate sample introduction system for water phase and oil phase - Google Patents
Accurate sample introduction system for water phase and oil phase Download PDFInfo
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- CN113092796A CN113092796A CN202110359383.1A CN202110359383A CN113092796A CN 113092796 A CN113092796 A CN 113092796A CN 202110359383 A CN202110359383 A CN 202110359383A CN 113092796 A CN113092796 A CN 113092796A
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 42
- 238000002347 injection Methods 0.000 claims abstract description 47
- 239000007924 injection Substances 0.000 claims abstract description 47
- 238000005070 sampling Methods 0.000 claims abstract description 9
- 239000000463 material Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 12
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 5
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 5
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 5
- 238000001746 injection moulding Methods 0.000 claims description 4
- 238000000465 moulding Methods 0.000 claims description 3
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims 1
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims 1
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010586 diagram Methods 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 241001272720 Medialuna californiensis Species 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000005370 electroosmosis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000011553 magnetic fluid Substances 0.000 description 1
- -1 polydimethylsiloxane Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1016—Control of the volume dispensed or introduced
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00178—Special arrangements of analysers
- G01N2035/00237—Handling microquantities of analyte, e.g. microvalves, capillary networks
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
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- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
The invention discloses an accurate sample introduction system aiming at water and oil phases, which consists of a controller, a stepping motor, a clamp, an injector, an oil phase, a suction head and a microfluidic chip, wherein the controller is connected with the stepping motor through a built-in interface, the stepping motor is connected with the injector, one end of the suction head is sleeved at the outlet of the injector, and the other end of the suction head is connected with the microfluidic chip. The injector drives the oil phase to flow so as to drive the water phase to flow, so that the problems of dead volume, pipeline blockage and the like caused in a microfluidic chip by a conventional injection sampling mode are solved, the simultaneous sampling of the water phase and the oil phase can be realized, and the injector is suitable for a microfluidic system which has sampling requirements on the water phase and the oil phase. The invention has the advantages of reasonable design, simple structure, high precision and strong stability, and can realize the sample introduction of water and oil phases. The invention can realize injection sample injection automatically or manually. The invention is suitable for the micro-fluidic chip which is used for common injection materials, and is particularly suitable for the micro-fluidic chip system which has the sample injection requirement on both water phase and oil phase.
Description
Technical Field
The invention belongs to the field of analysis and detection instruments and in-vitro diagnosis equipment, and relates to an accurate sample introduction system for water and oil phases, in particular to a high-precision and high-precision sample introduction device for a microfluidic chip.
Background
Microfluidic chip technology refers to chips capable of manipulating fluids on the micrometer scale. The micro-fluidic chip is generally only a few square centimeters in size, but can integrate basic operation units of sample preparation, reaction, separation, detection and the like in the processes of biological, chemical and medical analysis together to automatically complete the whole analysis process. The micro-fluidic chip is essentially an integrated module with a complex micro-channel network and a precise structure. At present, along with the technical development of precision injection molding, the requirement of micro-fluidic sample injection is developed towards the direction of higher precision and stronger stability.
The sample introduction system is used as an important functional module of the microfluidic system, and has very important significance in the aspects of accelerating the reaction speed, ensuring the detection stability and precision, improving the instrument stability, reducing the reagent dosage and the like. The micro-fluid driving method generally includes two driving methods, one is mechanical driving, and the driving method mainly utilizes an external mechanical part to achieve the purpose of driving the fluid in the chip, such as: various micropump drives such as piezoelectric micropumps, thermopneumatic micropumps, reciprocating micropumps and the like, and centrifugal force micropumps; the other type is a non-mechanical driving mode, and related mechanical parts are not arranged in the chip, and the chip comprises electroosmosis driving, gravity driving, magnetic fluid driving and the like.
However, these current mainstream sample injection methods cannot continuously drive the water phase and the oil phase into the microfluidic chip, and generate a large error when the sample injection volume is small, and require a precise pressure regulator to regulate the driving air pressure and flow rate, which results in high cost. Most of micro-fluidic chips need to accurately add an oil phase in addition to a water phase in the sample injection process, which puts certain requirements on the accurate sample injection control of the two phases of the water phase.
Disclosure of Invention
The invention aims to provide an accurate sample injection system for water and oil phases, which is a high-precision injection sample injection system, quantitatively samples trace water phases and trace oil phases required by a micro-fluidic chip, and simultaneously improves the sample injection accuracy and stability.
The invention provides an accurate sample introduction system for water and oil phases, which mainly comprises a controller, a stepping motor, a clamp, an injector, an oil phase, a suction head and a micro-fluidic chip. The controller is connected with a stepping motor through a built-in interface, the stepping motor is connected with the injector through a clamp, the clamp is half-moon-shaped, a fixed clamping opening is formed in the clamp and used for fixing the injector needle cylinder, a movable clamping opening is further formed in the clamp, one end of the movable clamping opening is connected with the stepping motor, the other end of the movable clamping opening is connected with a push rod of the injector, accordingly, the injector is sucked, a suction head is connected with the convex outlet end of the front end of the injector, one end of the suction head is connected with the convex outlet end of the front end of the injector, and the other end.
The principle of accurate sample injection is that a controller drives a stepping motor to control the speed, water phase interfacial tension is formed in an injector, then an oil phase drives the water phase to flow, distance-volume conversion control is performed, and accurate control of the water phase and the oil phase is finally realized.
The motor used by the invention is a stepping motor, the model can be DM542+57, 42BYGH34 and other common models, and the controller is a controller matched with the motor when leaving a factory. The change curve of the lifting speed of the motor can adopt exponential shape, linear shape, logarithmic shape and S shape, and finally adopts S-shaped motor curve acceleration.
The injector is a conventional injector with the specification of 1mL, is filled with an oil phase, and is filled with the oil phase and integrated with the oil phase.
The oil phase can be common oil phase which can form interfacial tension with water phase, such as silicone oil, paraffin oil, fluorine oil and the like.
The suction head is a common pipette suction head, and comprises specifications of 10 mu L, 200 mu L, 300 mu L, 1mL and the like.
The micro-fluidic chip is provided with a micro-channel structure and a micro-cavity array structure, is provided with a sample inlet matched with the suction head, and is provided with more than 1000 array cavities, and each cavity is connected through a micro-channel. The materials of the microfluidic chip can be selected from COC, COP, PDMS, PMMA and the like. The processing mode of the microfluidic chip can adopt conventional modes such as injection molding, hot press molding and the like.
Before the suction head is connected with the micro-fluidic chip, the syringe is firstly connected with the suction head, the syringe and the suction head are filled with oil phase, then the water phase is sucked after a certain volume of oil phase at the front end of the suction head is removed, and then the suction head is connected with a sample inlet of the micro-fluidic chip.
The invention discloses a use method of automatic injection sample introduction of a microfluidic system, which is realized by the following steps:
(1) the injector is connected with the suction head, and sucks the oil phase to ensure that the injector and the suction head are full of the oil phase, and sucks the water phase liquid after a certain volume is removed;
(2) the injector is connected with the stepping motor through the clamp, and the suction head is connected with a sample inlet of the microfluidic chip;
(3) starting the stepping motor to push the injector, and converting the speed parameter into a distance parameter and further into a volume parameter by the controller;
(4) the water phase firstly enters the micro-fluidic chip, and then the oil phase enters the micro-fluidic chip;
(5) and stopping the sample injection process after the set volume is reached.
The accurate sample introduction system can realize automatic injection sample introduction and can also realize manual sample introduction by utilizing the injector, the oil phase, the suction head and the microfluidic chip.
The invention has the beneficial effects that: (1) the sample injector provided by the invention drives the oil phase to flow through the injector so as to drive the water phase to flow, avoids the problems of poor stability, dead volume, easy gas blockage on a micro-fluidic chip and the like caused by air pressure driving, and can realize accurate control of liquid. (2) The sample injection microfluidic system provided by the invention can be realized automatically and manually, has the advantages of reasonable design, simple structure, high precision and strong stability, and can realize sample injection of water and oil phases. (3) The sample injection system provided by the invention is suitable for being applied to common micro-fluidic chips made of injection materials, such as PMMA (polymethyl methacrylate), COC (chip on chip), COP (coefficient of performance), PDMS (polydimethylsiloxane) and the like, and is particularly suitable for micro-fluidic chip systems with sample injection requirements on both water phase and oil phase.
Drawings
Fig. 1 is a schematic structural view of the present invention. Wherein the controller 1, the stepping motor 2, the clamp 4, the injector 5, the oil phase 7, the suction head 8 and the microfluidic chip 9.
Fig. 2 is a schematic diagram of the manual connection of the microfluidic chip and the syringe.
Fig. 3 is a schematic diagram of a microfluidic chip suitable for injection sampling. Wherein the sample inlet 10, the microchannel 11, the array chamber 12.
Detailed Description
The invention combines the attached drawings and the embodiment to explain the sample feeding system in detail.
Referring to fig. 1, an accurate sample injection system for water and oil phases mainly includes a controller 1, a stepping motor 2, a clamp 4, an injector 5, an oil phase 7, a suction head 8, and a microfluidic chip 9.
The stepping motor 2 pushes the injector to perform forward pushing and backward moving actions through the clamp.
The syringe 5 is pre-connected to a suction head 8 and filled with an oil phase 7.
One end of the suction head 8 is connected with the injector 5, and the other end is connected with the microfluidic chip 9. Before connecting with the micro-fluidic chip 9, the injector 5 and the suction head 8 are filled with oil phase, and then a certain volume of oil phase (about 20-50 μ L) is removed, and then the water phase is sucked, so as to complete the assembly of the injection part.
Referring to fig. 3, the microfluidic chip 9 has a microchannel structure and a microcavity array structure, has a sample inlet 10 at one end matching with the outlet end of the tip 8 or syringe, and has more than 1000 array chambers 12, each connected by a microchannel 11. The material of the micro-fluidic chip can be selected from COC, COP, PDMS, PMMA and the like. The processing mode of the microfluidic chip can adopt conventional modes such as injection molding, hot press molding and the like.
The process of sample injection is completed by pushing a push rod of the injector to move forward by the stepping motor, and pushing the water phase to move forward after the oil phase is pushed forward.
Referring to fig. 2, the injector 5, the oil phase 7, the suction head 8 and the microfluidic chip 9 of the present invention can also be used for realizing a manual injection sampling mode.
Example 2 automatic in-chip injection of PCR reaction reagents and oil phase
(1) Firstly, connecting a syringe 5 with a suction head 8, and fixing the syringe on a clamp 4;
(2) starting the controller 1, controlling the injector 5 to absorb the oil phase 7 by using the stepping motor 2, and removing the volume of 20 mu L after full absorption;
(3) the controller 1 controls the injector to absorb 20 mu L of PCR reaction solution through the stepping motor 2 and is connected with the sample inlet 10 of the microfluidic chip 9;
(4) the stepping motor 2 controls the injector 5 to push the oil phase 7 and further push the PCR reaction solution to enter the microfluidic chip 9;
(5) after entering the microfluidic chip 9, the PCR reaction solution enters the array chamber 12 along the microchannel 11, and then the oil phase 7 enters the microfluidic chip 9 and enters the array chamber 12 through the microchannel 11.
(6) And after the sample introduction is finished, stopping the movement of the stepping motor through the controller.
Example 3 Manual in-chip injection of PCR reaction reagents and oil phase
(1) The injector is connected with the suction head and is full of oil phase, and water phase liquid is sucked after a certain volume (about 20-50 mu L) is discharged;
(2) the suction head is connected with a sample inlet of the microfluidic chip;
(3) a push rod of the injector is manually pushed, the water phase firstly enters the micro-fluidic chip, and then the oil phase enters the micro-fluidic chip;
(4) and after the set volume is reached, stopping manual injection and finishing sample injection.
Claims (9)
1. The utility model provides a to two-phase accurate sampling system of water oil, its characterized in that comprises controller (1), step motor (2), anchor clamps (4), syringe (5), oil phase (7), suction head (8), micro-fluidic chip (9), controller (1) is through built-in interface connection step motor (2), step motor (2) are through anchor clamps (4) connection syringe (5), suction head (8) are connected with syringe (5) front end convex exit end, micro-fluidic chip (9) link to each other with syringe (5) through suction head (8).
2. The microfluidic system for injection sampling according to claim 1, wherein the clamp (4) of the clamp (4) is half-moon-shaped, a fixed clamp port (6) is provided on the clamp (4) for fixing the injector (5), the clamp (4) is further provided with a movable clamp port (3), one end of the movable clamp port (3) is connected with the stepping motor, and the other end of the movable clamp port (3) is connected with the push rod of the injector.
3. The precise sample injection system for water and oil phases as claimed in claim 1, wherein the micro-fluidic chip (9) is provided with a sample injection port (10) matched with the suction head (8) or the front outlet of the injector, more than 1000 array chambers (12), and each array chamber is connected through a micro-channel (11).
4. The system for precise sample injection for water and oil phases as claimed in claim 1, wherein the material of the microfluidic chip (9) is COC, COP, PDMS, PMMA.
5. The microfluidic system for injection sampling according to claim 1, wherein the microfluidic chip (9) is processed by conventional injection molding or hot press molding.
6. The system according to claim 1, wherein before the connection suction head (8) is connected to the microfluidic chip (9), the injector (5) is connected to the suction head (8) first, so that the injector (5) and the suction head (8) are filled with the oil phase (7), then the water phase is sucked after a certain volume of the oil phase at the front end of the suction head (8) is removed, and then the suction head (8) is connected to the sample inlet (10) of the microfluidic chip (9).
7. A precise sample injection system for water and oil phases according to claim 6, characterized in that the volume of the oil phase excluding the front end of the suction head (8) is 20-50 μ L.
8. The accurate sample injection system for the two phases of water and oil in claim 1 is characterized in that the automatic injection sample injection mode is realized by the following steps:
(1) the injector is connected with the suction head and is full of oil phase, and water phase liquid is sucked after a certain volume is discharged;
(2) the injector is connected with the stepping motor through the clamp, and the suction head is connected with a sample inlet of the microfluidic chip;
(3) starting the stepping motor to push the injector, and converting the speed parameter into a distance parameter and further into a volume parameter by the controller;
(4) the water phase firstly enters the micro-fluidic chip, and then the oil phase enters the micro-fluidic chip.
(5) And stopping the sample injection process after the set volume is reached.
9. The use method of the precision sample injection system for the two phases of water and oil in claim 1 is characterized in that the manual injection sample injection mode is realized by the following steps:
(1) the injector is connected with the suction head and is full of oil phase, and water phase liquid is sucked after a certain volume is discharged;
(2) the suction head is connected with a sample inlet of the microfluidic chip;
(3) a push rod of the injector is manually pushed, the water phase firstly enters the micro-fluidic chip, and then the oil phase enters the micro-fluidic chip;
(4) and after the set volume is reached, stopping manual injection and finishing injection.
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| 郭肖杰: "《高通量自动化微生物微液滴进化培养与筛选技术及其装备化》", 《生物工程学报》, vol. 37, no. 3, pages 991 - 1003 * |
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