CN110095624B - Device and method for detecting and removing bubbles during sample injection - Google Patents

Device and method for detecting and removing bubbles during sample injection Download PDF

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Publication number
CN110095624B
CN110095624B CN201910337798.1A CN201910337798A CN110095624B CN 110095624 B CN110095624 B CN 110095624B CN 201910337798 A CN201910337798 A CN 201910337798A CN 110095624 B CN110095624 B CN 110095624B
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sensor
detecting
pump
sample injection
cylinder
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CN110095624A (en
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陈勇
石剑
韩超
周威
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Guangzhou Anfang Biotechnology Co ltd
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Guangzhou Anfang Biotechnology Co ltd
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D19/00Degasification of liquids
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584Control arrangements for automatic analysers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1002Reagent dispensers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009Characterised by arrangements for controlling the aspiration or dispense of liquids
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016Control of the volume dispensed or introduced
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016Control of the volume dispensed or introduced
    • G01N2035/1018Detecting inhomogeneities, e.g. foam, bubbles, clots
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N2035/1025Fluid level sensing
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/1034Transferring microquantities of liquid

Abstract

The invention discloses a device for detecting and removing bubbles during sample introduction, which comprises a feeding cylinder, a first sensor, a containing cavity, a pump and a control assembly. The cavity is provided with an input end and an output end, the feeding cylinder comprises a cylinder body and a cylinder head with the cross section size smaller than that of the cylinder body, and the feeding cylinder is connected with the input end through the cylinder head. The output is connected to the pump, and first sensor is located section of thick bamboo head position department and is used for detecting the bubble, and pump and first sensor all connect the control assembly. The device for detecting and removing the bubbles in the sample introduction process is simple in structure, efficient and practical, and effectively guarantees the addition amount of liquid materials. The liquid flow at the position of the cylinder head is detected through the first sensor, and the section size of the cylinder head is small, so that the sensitivity is high, the pump is started to reversely push the bubbles out of the cylinder body and eliminate the bubbles after the bubbles are detected, and the flow is simple and convenient. The invention is used in the field of liquid sample collection and detection.

Description

Device and method for detecting and removing bubbles during sample injection
Technical Field
The invention relates to the field of liquid sample collection and detection, in particular to a device and a method for detecting and removing bubbles during sample injection.
Background
In some scientific research experiments and production processes, the addition of some liquid materials is often involved. In many liquid material adding processes, in order to control the adding amount of the liquid material relatively well, the liquid material is usually added through a pipe or a syringe. However, air may be incorporated during the addition of the liquid material, resulting in the generation of bubbles. Many times, the caliber of the device such as the pipeline or the syringe is small, and the air bubbles cannot be automatically eliminated and can flow in the device such as the pipeline or the syringe. Particularly for the syringe device, because the diameter of the syringe barrel body and the diameter of the syringe head are transitional, and the diameter of the syringe head is small, air bubbles are easy to generate and are difficult to eliminate. The addition amount of the liquid material is calculated by volume, and the existence of the air bubbles can influence the calculation of the addition amount of the liquid material and the addition precision of the liquid material. Meanwhile, the gas in the bubbles can cause great influence on scientific research experiments and production and processing, and cause poor experimental effect or low production quality.
Disclosure of Invention
The invention aims to provide a convenient and practical sample injection bubble detection and removal device and a simple and efficient method applying the sample injection bubble detection and removal device.
The technical scheme adopted by the invention is as follows: the utility model provides a device that bubble detected and got rid of when advancing kind, includes a feeding section of thick bamboo, first sensor, holds chamber, pump machine and control assembly, is equipped with input and output on holding the chamber, and a feeding section of thick bamboo includes barrel head that barrel body and cross sectional dimension are less than the barrel body, and a feeding section of thick bamboo passes through the barrel head and connects the input, and the output is connected to the pump machine, and the detection end of first sensor is located barrel head position department and is used for detecting the bubble, and first sensor and pump machine all connect control assembly.
As an improvement of the scheme, the accommodating cavity is a micro-fluidic chip, and the feeding cylinder is a needle cylinder.
As an improvement of the scheme, the device also comprises a second sensor which is connected with the control assembly and used for detecting the liquid level of the cylinder body, and the detection end of the second sensor is positioned at the lower side position of the cylinder body.
As an improvement of the scheme, the device further comprises a clamp, the clamp comprises a first clamping block and a second clamping block which are connected, a clamping seat for clamping the needle cylinder is arranged in the first clamping block, a cavity for fixing the micro-fluidic chip is arranged on the second clamping block, and the cavity is opened upwards to expose the input end and the output end of the micro-fluidic chip.
As an improvement of the scheme, the first sensor and the second sensor are respectively positioned on the second clamping block and the first clamping block.
As an improvement of the above, the first sensor and the second sensor are both of a correlation type photoelectric sensor.
As an improvement of the scheme, the microfluidic chip comprises an upper cover plate and a lower cover plate, a liquid path is arranged between the upper cover plate and the lower cover plate, and an input end and an output end are positioned on the upper cover plate and are communicated with the liquid path.
As the improvement of the scheme, the height of the chamber is 500-1000 um higher than the thickness of the microfluidic chip, and the upper side and the lower side in the chamber are both provided with elastic materials.
In the sample introduction process, the pump operates to suck the sample into the containing cavity, the control assembly acquires the condition of the sample in the cylinder head through the first sensor, when the first sensor detects that the position of the cylinder head has the bubble, the pump is started to firstly push the bubble back to the cylinder body in a reverse pushing mode, and then the pump operates again to suck the sample into the containing cavity.
As an improvement of the scheme, the volume of the reverse pushing liquid of the pump is 10-1000 ul.
The invention has the beneficial effects that: the device for detecting and removing the bubbles in the sample feeding process is characterized in that an input end and an output end are arranged on a containing cavity, the input end and the output end are respectively connected with a feeding barrel and a pump machine, the feeding barrel comprises a barrel body and a barrel head, the cross section of the barrel head is smaller than that of the barrel body, the barrel body is partially used for storing liquid materials and enters the input end through the barrel head, a first sensor for detecting the bubbles is arranged at the position of the barrel head, the first sensor can accurately detect the bubbles in the barrel head, and the bubbles are pushed out of the barrel head by the pump machine, so that the device is simple in structure, efficient and practical, the problem that the bubbles are easily generated in the traditional liquid material adding process is solved, the adding amount of the liquid materials is effectively ensured, and the experimental effect and the production quality are ensured; the first sensor is used for detecting liquid flow at the position of the cylinder head, the section size of the cylinder head is small, the sensitivity of the first sensor is high, the pump is started by the control assembly after the bubbles are detected, the bubbles are pushed out to the cylinder body in a reverse pushing mode, and the bubbles can float and escape due to the fact that the section size of the cylinder body is large, so that the bubbles generated during sample injection are removed, and the method is simple and convenient in flow.
Drawings
The invention will be further described with reference to the accompanying drawings in which:
FIG. 1 is a schematic front view of the apparatus;
FIG. 2 is a schematic view of the back side of the device;
FIG. 3 is a schematic view of the structure of the clamp of the apparatus;
FIG. 4 is an exploded view of the clamp;
fig. 5 is a top view of the microfluidic chip.
Detailed Description
Referring to fig. 1 to 5, the invention relates to a device for detecting and removing bubbles during sample injection, which comprises a feeding cylinder, a first sensor 322, a cavity, a pump and a control component. The feeding cylinder comprises a cylinder body and a cylinder head with the section size smaller than that of the cylinder body, the feeding cylinder is usually arranged in the vertical direction, openings are arranged at the upper end and the lower end of the feeding cylinder, the upper end opening is located on the upper side of the cylinder body, and the lower end opening is located on the lower side of the cylinder body. The opening at the upper end is significantly larger than the opening at the lower end, and generally the material to be added enters through the opening at the upper end and flows from the opening at the lower end to the input end of the chamber. The chamber referred to herein is a member having a space for storing liquid or a space for flowing liquid, and the chamber is generally provided with only an input terminal and an output terminal which can be connected to the outside, and the input terminal and the output terminal respectively input and output liquid to and from the inside of the chamber. The feeding cylinder is connected with the input end through the cylinder head, the pump is connected with the output end, and the connection positions of the feeding cylinder and the input end as well as the pump and the output end are respectively and tightly connected, so that leakage is avoided. A first sensor 322 for detecting bubbles is provided at the cartridge head position, and the first sensor 322 detects bubbles by differentiating some properties of the liquid material and the bubbles. The gas bubbles can be small bubbles or relatively large bubbles that cause a discontinuity in the flow of the liquid material. The control assembly is generally configured to receive signals from the first sensor 322 and control the operation of the pump. The control component can be a single chip microcomputer, a processor or an external computer and the like. Preferably, the feeding cylinder is transparent, the first sensor 322 is a correlation type photoelectric sensor, and the transmitter and the receiver of the first sensor 322 are respectively positioned at two sides of the cylinder head.
In a preferred embodiment, the cavity is a microfluidic chip 12, and the feeding cylinder is a syringe 11. Relatively speaking, the device for detecting and removing bubbles in sample introduction can be used for adding more accurate liquid materials, and can achieve good effect on the micro-fluidic chip 12 in the process of adding experiments on the micro-liquid materials. The feeding cylinder can be directly selected from the needle cylinder 11, is simple and easy to obtain, and can have relatively uniform standard, and the cross-sectional shapes of the cylinder head and the cylinder body are both circular.
As a preferred embodiment, a clamp is further included, and the clamp can stabilize the relative position of the syringe 11 and the microfluidic chip 12. The fixture comprises a first fixture block 31 and a second fixture block 32 which are connected, wherein the first fixture block 31 is used for fixing the syringe 11, and the second fixture block 32 is used for fixing the microfluidic chip 12. The first latch 31 is usually fixed to the upper end of the second latch 32 by screws, so as to ensure that the syringe 11 can be inserted vertically into the input end while being upright. The first engaging block 31 is provided with an engaging seat 312 for engaging the syringe 11, and the engaging seat 312 is provided with a U-shaped member for surrounding and holding the syringe body of the syringe 11. The clamping seat 312 can effectively fix the syringe 11, and prevent the first sensor 322 from detecting inaccurately due to the inclination of the syringe 11. And a cavity 321 for fixing the microfluidic chip 12 is formed in the second fixture block 32, and the cavity 321 is opened upwards to expose the input end and the output end of the microfluidic chip 12.
In a preferred embodiment, a second sensor 313 for detecting the liquid level of the cylinder is arranged at the position of the cylinder, and the detection end of the second sensor 313 is positioned at the lower side of the cylinder. The second sensor 313 can detect the liquid level in the syringe 11, usually ensuring that the liquid level is 2-5 mm higher than the upper end of the syringe head, detecting the sample without accurate control of the liquid amount through the second sensor 313, and stopping the operation of the syringe pump 21 by the control assembly after detecting the signal. Because the section size of the syringe body is larger, the second sensor 313 detects and controls the liquid level in the syringe 11 to be always higher than the syringe head by 2-5 mm, so that the reagent can be prevented from being diluted, and the generation of bubbles can be effectively reduced. Preferably, the first sensor 322 and the second sensor 313 are located on the second latch 32 and the first latch 31, respectively. The second sensor 313 is also a correlation type photoelectric sensor, the detection end of which is a transmitter and a receiver, and the transmitter and the receiver are connected through the axis of the cylinder body. Preferably, both the second sensor 313 and the cartridge 312 are mounted in the first cartridge 31 from the back side of the first cartridge 31, which may facilitate maintenance and may select different cartridges 312 to be mounted according to the barrel model of the syringe 11. A backing plate 311 is typically disposed in first cartridge 312, and may further bear against second sensor 313 and cartridge 312. First sensor 322 is also mounted into second cartridge 32 from the back side of second cartridge 32.
Correspondingly, in the method for applying any device for detecting and removing bubbles during sample injection, in the sample injection process, the pump operates to suck the sample into the cavity, the control assembly acquires the condition of the sample in the cylinder head through the first sensor 322, when the first sensor 322 detects that bubbles exist at the position of the cylinder head, the pump firstly pushes the bubbles back to the cylinder body in a reverse pushing mode, and then the pump operates again to suck the sample into the cavity. The detection of the first sensor 322 at the cylinder head position can effectively ensure the detection accuracy, and the liquid flow section is reduced to improve the sensitivity. The control is generally performed by a control assembly, which receives the signal from the first sensor 322 and then uses a pump to push the bubbles back into the barrel. The pump machine with higher precision can be selected as the pump machine, and the corresponding volume is pushed back to move the bubbles out of the barrel head according to the volume of the inner cavity of the barrel head. Because the diameter of the cylinder body is obviously larger than that of the cylinder head, air bubbles can escape from the cylinder body. Preferably, the volume of the pump reverse-pushing liquid is 10-1000 ul.
In this embodiment, the microfluidic chip 12 of the apparatus for detecting and removing bubbles during sample injection includes an upper cover plate and a lower cover plate, and a liquid path is provided between the upper cover plate and the lower cover plate. For the fluidic chip 12 used for cell separation and staining, the liquid path is designed to be small and has a filtering function. Usually, the input end and the output end are located at two ends of the liquid path, and the input end and the output end are both arranged on the upper cover plate and are both provided with projections with slotted holes, and the slotted holes are communicated with the liquid path. The head of the needle cylinder 11 can be inserted into a slot in the projection of the input and the pump is connected to the output by means of a line 22 through a pagoda joint. Preferably, the height is 500-1000 um higher than the thickness of the microfluidic chip 12, and the upper and lower sides in the chamber 321 are both provided with elastic materials. The microfluidic chip 12 may be pushed into the chamber 321, and the elastic material on the upper and lower sides of the chamber 321 is used to compress the microfluidic chip 12. Preferably, the pump is a syringe pump 21, and the liquid material in the barrel is introduced into the fluidic chip 12 by pumping the liquid material from the output end by the syringe pump 21. The injection pump 21 can effectively improve the material adding precision and ensure the stability of the device operation.
In the method, the liquid material to be added into the microfluidic chip 12 is added into the barrel. The syringe pump 21 is started to pump liquid material from the output end through the pipeline 22, the liquid in the cylinder body is pumped to the micro-fluidic chip 12 from the cylinder head through the input end, and the first sensor 322 and the second sensor 313 are always in a starting state for detection in the process. This is prone to some bubble formation because the diameter of the barrel is larger than the diameter of the cartridge head and typically the dimensions are relatively large apart. When the first sensor 322 detects a bubble, the control assembly receives a signal from the first sensor 322 and the control assembly stops the syringe pump 21 from drawing the liquid material and pushes the liquid material in the opposite direction. The liquid material originally in the cartridge head position is typically pushed back into the cartridge body. Due to the larger diameter of the barrel, the bubbles will escape the liquid material due to buoyancy. The second sensor 313 can detect the liquid level in the syringe 11, usually ensuring that the liquid level is 2-5 mm higher than the upper end of the syringe head, detecting the sample without accurate control of the liquid amount through the second sensor 313, and stopping the operation of the syringe pump 21 by the control assembly after detecting the signal. Therefore, the liquid level can be kept higher than the cylinder head all the time, and the generation of bubbles can be effectively avoided. The specific value of the liquid level detected by the second sensor 313 is arranged at the position of the lower end of the cylinder body close to the cylinder head, but is slightly higher than the cylinder head, so that the mutual dilution of front and back two liquid materials can be avoided, and the accurate sample introduction of the liquid material volume is further ensured.
Of course, the design creation is not limited to the above embodiments, and the combination of different features of the above embodiments can also achieve good effects. Those skilled in the art can make equivalent variations or substitutions without departing from the spirit of the invention, and such equivalent variations or substitutions are included within the scope of the invention as defined by the claims.

Claims (9)

1. A method for detecting and removing bubbles during sample injection adopts a device for detecting and removing bubbles during sample injection, and is characterized in that: the air bubble detection device comprises a feeding barrel, a first sensor (322), a containing cavity, a pump and a control assembly, wherein the containing cavity is provided with an input end and an output end, the feeding barrel comprises a barrel body and a barrel head with the section size smaller than that of the barrel body, the feeding barrel is connected with the input end through the barrel head, the pump is connected with the output end, a detection end of the first sensor (322) is located at the position of the barrel head and used for detecting bubbles, and the first sensor (322) and the pump are both connected with the control assembly;
the method for detecting and removing bubbles during sample injection comprises the following steps:
in the sampling process, the pump operates to suck a sample into the cavity, the control assembly obtains the condition of the sample in the cylinder head through the first sensor (322), when the first sensor (322) detects that bubbles exist at the position of the cylinder head, the pump firstly pushes the bubbles back to the cylinder body in a reverse pushing mode, and then the pump operates again to suck the sample into the cavity.
2. The method for detecting and removing bubbles during sample injection according to claim 1, wherein the method comprises the following steps: the cavity is a microfluidic chip (12), and the feeding cylinder is a needle cylinder (11).
3. The method for detecting and removing bubbles in sample injection according to claim 2, wherein the method comprises the following steps: the liquid level detection device further comprises a second sensor (313) connected with the control assembly and used for detecting the liquid level of the cylinder body, and a detection end of the second sensor (313) is located at the position of the lower side of the cylinder body.
4. The method for detecting and removing bubbles in sample injection according to claim 3, wherein the method comprises the following steps: the device is characterized by further comprising a clamp, wherein the clamp comprises a first clamping block (31) and a second clamping block (32) which are connected, a clamping seat (312) for clamping the needle cylinder (11) is arranged in the first clamping block (31), a chamber (321) for fixing the micro-fluidic chip (12) is arranged on the second clamping block (32), and an upward opening of the chamber (321) exposes the input end and the output end of the micro-fluidic chip (12).
5. The method for detecting and removing bubbles during sample injection according to claim 4, wherein the method comprises the following steps: the first sensor (322) and the second sensor (313) are respectively positioned on the second fixture block (32) and the first fixture block (31).
6. The method for detecting and removing bubbles during sample injection according to claim 5, wherein the method comprises the following steps: the first sensor (322) and the second sensor (313) are both of a correlation type photoelectric sensor.
7. The method for detecting and removing bubbles during sample injection according to claim 6, wherein the method comprises the following steps: the microfluidic chip (12) comprises an upper cover plate and a lower cover plate, a liquid path is arranged between the upper cover plate and the lower cover plate, and the input end and the output end are positioned on the upper cover plate and are communicated into the liquid path.
8. The method for detecting and removing bubbles in sample injection according to claim 7, wherein the method comprises the following steps: the height of the cavity (321) is 500-1000 um higher than the thickness of the microfluidic chip (12), and elastic materials are arranged on the upper side and the lower side of the cavity (321).
9. The method for detecting and removing bubbles during sample injection according to claim 1, wherein the method comprises the following steps: the volume of the reverse pushing liquid of the pump is 10-1000 ul.
CN201910337798.1A 2019-04-25 2019-04-25 Device and method for detecting and removing bubbles during sample injection Active CN110095624B (en)

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Publication number Priority date Publication date Assignee Title
CN102735864A (en) * 2012-06-28 2012-10-17 中国人民解放军军事医学科学院卫生学环境医学研究所 Hand-operated air pressure sample introduction method for microfluidic chips
CN104166008A (en) * 2014-08-11 2014-11-26 江苏大学 Automatic synchronous sample introduction method and device for micro-fluidic chip
CN207877718U (en) * 2018-01-18 2018-09-18 江苏省肿瘤防治研究所(江苏省肿瘤医院) The micro-fluidic sampling device of bubble-free of cell solution

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