CN113866158B - Particle detection device and operation method thereof - Google Patents
Particle detection device and operation method thereof Download PDFInfo
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- CN113866158B CN113866158B CN202111006391.4A CN202111006391A CN113866158B CN 113866158 B CN113866158 B CN 113866158B CN 202111006391 A CN202111006391 A CN 202111006391A CN 113866158 B CN113866158 B CN 113866158B
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- 238000000034 method Methods 0.000 title claims abstract description 18
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- 239000007788 liquid Substances 0.000 claims abstract description 185
- 238000002347 injection Methods 0.000 claims abstract description 65
- 239000007924 injection Substances 0.000 claims abstract description 65
- 238000007789 sealing Methods 0.000 claims abstract description 37
- 239000012530 fluid Substances 0.000 claims abstract description 10
- 238000005070 sampling Methods 0.000 claims abstract description 8
- 239000000758 substrate Substances 0.000 claims description 28
- 238000012360 testing method Methods 0.000 claims description 4
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- 239000000523 sample Substances 0.000 description 264
- 239000003550 marker Substances 0.000 description 14
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- 239000012472 biological sample Substances 0.000 description 5
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- 108091007433 antigens Proteins 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
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- 238000004458 analytical method Methods 0.000 description 2
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- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent 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
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/76—Chemiluminescence; Bioluminescence
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
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- Sampling And Sample Adjustment (AREA)
Abstract
The embodiment of the application discloses a particle detection device and operation method thereof, the particle detection device includes a base plate and at least one detection unit arranged on the base plate, the at least one detection unit includes: a detection cell, the detection cell being capable of containing a sample fluid; the sample injection part is communicated with the detection pool, the sample injection part can be in sealing connection with the liquid driving device, and the liquid driving device is matched with the sample injection part to enable the sample liquid to enter and exit the detection pool. The sampling part of the particle detection device can be matched with the liquid driving device in a sealing way, and sample liquid can be rapidly led in and led out of the detection tank.
Description
Technical Field
The present disclosure relates to the field of biological detection technologies, and in particular, to a particulate detection device and an operation method thereof.
Background
The particle detection device can be used for detecting biological samples, and a target object to be detected in the biological samples is detected or separated by using a specific marker. The particle detection device can use suitable markers according to different target objects to be detected in the sample, and has wide application in the fields of clinical examination, medicine analysis, environmental monitoring and the like.
Disclosure of Invention
One of the embodiments of the present specification provides a particulate detection device including a substrate and at least one detection unit provided on the substrate, the at least one detection unit including: a detection cell, the detection cell being capable of containing a sample fluid; the sample injection part is communicated with the detection pool, the sample injection part can be in sealing connection with the liquid driving device, and the liquid driving device is matched with the sample injection part to enable the sample liquid to enter and exit the detection pool.
In some embodiments, the sample introduction portion includes a sample introduction channel and a sample introduction port communicating with the detection cell through the sample introduction channel.
In some embodiments, the inner diameter of the sample channel gradually decreases along the direction from the sample inlet to the detection cell.
In some embodiments, the inner contour of the sample introduction channel is cone-shaped.
In some embodiments, the substrate includes a first plate and a second plate; the detection pool is arranged on the second plate body; the sample inlet is arranged on the first plate body; the sample introduction channel is arranged on the first plate body or the sample introduction channel is arranged on the first plate body and the second plate body.
In some embodiments, the axis of the sample introduction channel forms an included angle of 20-60 ° with the first plate.
In some embodiments, the first plate and the second plate are in a sealed arrangement, the detection cell is located between the first plate and the second plate, and the sample injection channel communicates the detection cell with the sample injection port.
In some embodiments, the sample inlet has an oval or circular shape in a cross section parallel to the first plate body.
In some embodiments, the sample inlet has a minor axis length of 0.5-4mm in the elliptical cross-section.
In some embodiments, the sample inlet protrudes from the first plate.
In some embodiments, the height of the sample inlet protruding from the first plate body is 0.5-3mm.
In some embodiments, the sample introduction channel has a length greater than 1mm.
In some embodiments, the sample introduction portion further comprises an elastic seal provided with a through hole, the elastic seal being mounted within the sample introduction channel and/or on the sample introduction port.
In some embodiments, the detection cell has a depth of less than 2mm.
In some embodiments, the sample injection portion and/or the detection tank are pre-embedded with a marker, and at least part of the marker is mixed into the sample liquid entering and exiting the detection tank by the cooperation of the liquid driving device and the sample injection portion.
One of the embodiments of the present application also provides a method of operating the above particulate detection device, the method comprising: introducing sample liquid into the detection pool through the sample introduction part; providing liquid driving force through a liquid driving device which is connected with the sample injection part in a sealing way, so that at least part of the sample liquid repeatedly enters and exits the detection pool; and driving the sample liquid to flow into the detection cell again through the liquid driving device.
In some embodiments, the driving force output part of the liquid driving device is inserted into and presses the sample introduction part, so that the liquid driving device is in sealing connection with the sample introduction part.
In some embodiments, the liquid driving device drives at least part of the sample liquid to repeatedly enter and exit the detection cell at least 1 time, so that at least part of the markers pre-embedded in the sample injection part or the detection cell are mixed with the sample liquid.
In some embodiments, the liquid drive device is a device with positive and negative pressure control; the device with positive and negative pressure control is one of a pipettor, a syringe and a skin-blowing device.
Drawings
The present specification will be further elucidated by way of example embodiments, which will be described in detail by means of the accompanying drawings. The embodiments are not limiting, in which like numerals represent like structures, wherein:
FIG. 1 is a schematic perspective view of a particle detection apparatus according to some embodiments of the present disclosure;
fig. 2 is a front view of a first plate body of a particle detection apparatus according to some embodiments of the present specification, wherein the particle detection apparatus is provided with a plurality of detection units;
FIG. 3 is a front view of a particulate detection device according to some embodiments of the present disclosure;
FIG. 4 is a cross-sectional view taken along the direction A-A in FIG. 3;
FIG. 5 is an enlarged schematic view of B in FIG. 4;
fig. 6 to 11 are cross-sectional views of sample injection portions of a particle detection apparatus according to some embodiments of the present disclosure;
FIG. 12 is a cross-sectional view of a particulate detection device according to some embodiments of the present disclosure;
FIG. 13 is a cross-sectional view of a particulate detection device according to some embodiments of the present disclosure;
in the figure: 100-first plate, 200-second plate, 300-detection unit, 310-detection cell, 320-sample inlet, 321-sample inlet, 322-sample channel, 323-flange, 324-elastic seal, 325-plunger, 326-plunger cavity, 326 a-first plunger cavity, 326 b-second plunger cavity, 327-partition flap, 328-sealing plug, 329-mixing channel, 330-vent.
Detailed Description
Reference will now be made in detail to exemplary embodiments or implementations, examples of which are illustrated in the accompanying drawings. When the following description refers to the accompanying drawings, the same numbers in different drawings refer to the same or similar elements, unless otherwise indicated. The implementations described in the following exemplary examples are not representative of all implementations consistent with the present application. Rather, they are merely examples of apparatus and methods consistent with some aspects of the present application as detailed in the accompanying claims.
The terminology used in the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. As used in this application and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.
It should be understood that the terms first, second and the like used in the description and the claims do not denote any order, quantity or importance, but rather are used to distinguish one element from another. Likewise, the terms "a" or "an" and the like do not denote a limitation of quantity, but rather denote the presence of at least one. Unless otherwise indicated, the terms "front," "rear," "lower," and/or "upper" and the like are merely for convenience of description and are not limited to one location or one spatial orientation. The word "comprising" or "comprises", and the like, means that elements or items appearing before "comprising" or "comprising" are encompassed by the element or item recited after "comprising" or "comprising" and equivalents thereof, and that other elements or items are not excluded.
According to the difference between the marker and the target object in the sample, the application scenario of the particle detection apparatus may generally include: 1) And (5) clinical examination. For example, cell identification, cell counting, cell viability detection, cell cycle detection, apoptosis detection, etc. are performed using specific dye binding to cells; the method comprises the steps of utilizing a chemiluminescent related substance to label an antibody or an antigen, separating a free chemiluminescent label after reacting with the antigen or the antibody to be detected, and adding other related substances of a chemiluminescent system to produce a chemical reaction to perform quantitative or qualitative immunodetection of the antigen or the antibody. 2) And (5) drug analysis. For example, a specific detection reagent is used as a marker to be mixed with a biological sample such as a blood sample, a urine sample, or the like to detect a drug component and its concentration in the biological sample. 3) And (5) environmental monitoring. For example, detection and quantification of microorganisms in environmental biological samples is performed using specific dyes as labels capable of a detectable color change in the presence of one or more microorganisms.
For the observation and/or detection of micro-samples in a particle detection device, the cell thickness and the flow channel inner diameter of the particle detection device are typically between tens to hundreds of micrometers. Once the sample fluid enters the detection cell of the particulate detection device, it is difficult to conduct it out. Accordingly, it is desirable to provide a particulate detection device that can rapidly draw or aspirate sample fluid from a detection cell. According to the particle detection device, sample liquid can be rapidly led out or sucked from the detection pool by arranging the sample injection part capable of being matched with the liquid driving device in a sealing mode.
Hereinafter, a particulate detection device and an operation method thereof according to an embodiment of the present application will be described in detail with reference to fig. 1 to 13. It is noted that the following examples are only for the purpose of explaining the present application and are not to be construed as limiting the present application.
In some embodiments, the particulate detection device may include a substrate and one or more detection units 300 disposed on the substrate, each detection unit 300 may include a detection cell 310 and a sample introduction portion 320 in communication with the detection cell 310. The sample introduction part 320 is a main structure for introducing and discharging a sample liquid in cooperation with the liquid driving device, and the particle detection device can introduce the sample liquid to be detected into the detection cell 310 through the sealing cooperation of the sample introduction part 320 and the liquid driving device, and can discharge or suck the sample liquid from the detection cell 310 through the sample introduction part 320 and the liquid driving device.
The substrate is the main body structure of the particle detection device. The substrate may be an integrally formed structure or a multi-layer connection structure. In some embodiments, for ease of manufacturing, as shown in fig. 1-2, the substrate may include a first plate 100 and a second plate 200, and at least part of the structure of the detection unit 300 is disposed between the first plate 100 and the second plate 200. Further, in some embodiments, the first plate 100 and the second plate 200 of the substrate are in a sealed arrangement. For example, the first plate body 100 and the second plate body 200 may be sealed and connected by bonding, laser welding, ultrasonic welding, plasma treatment, or the like.
The inspection unit 300 is a collection of structures or components on a substrate that cooperate to perform a predetermined inspection. In some embodiments, a detection unit 300 may be disposed on the substrate. In some embodiments, as shown in fig. 3, a plurality of detection units 300 may be disposed on the substrate, so that the particle detection apparatus may perform detection of a plurality of samples, or detection of a plurality of samples at the same time. Considering that the detection device is disposable, in order to be convenient for calculating experimental design and controlling consumption of consumable, and considering the convenience of use and the limitation of the size of the substrate, 1-10 detection units 300 can be preferably arranged on the substrate.
The detection cell 310 can hold a sample fluid and is the primary site for optical detection. The sample liquid is collected in the detection cell 310, and the optical detection device detects the sample liquid through the detection cell 310. In some embodiments, the detection cell 310 is disposed on the second plate 200, such that the detection cell 310 between the first plate 100 and the second plate 200 forms a relatively closed detection environment through the sealed connection of the first plate 100 and the second plate 200. In some embodiments, the first plate 100 and/or the second plate 200 are configured to allow light to be transmitted into the detection cell 310 and to allow the optical detection device to detect light transmitted out of the detection cell 310. In some embodiments, the depth of the detection cell 310 is preferably less than 2mm. The preferable depth of the detection pool 310 can avoid the overlapping of the object to be detected in the sample liquid in the depth direction of the detection pool 310 as much as possible, and ensure the detection accuracy.
The sample solution to be measured is introduced into the detection cell 310 through the sample introduction portion 320 and is guided out/sucked out. In some embodiments, the sample introduction portion 320 can be in sealing connection with a liquid driving device, and the cooperation of the liquid driving device and the sample introduction portion 320 is used to make the sample liquid enter and exit the detection cell 310. Specifically, the sample feeding portion 320 is connected with the liquid driving device in a sealing manner, so that the liquid driving force provided by the liquid driving device can effectively act on the sample liquid entering the detection unit 300, and the sample liquid can repeatedly enter and exit the detection cell 310 under the action of the liquid driving force. In some embodiments, the liquid drive device may be one of a pipette, a syringe, and a skin blow. Preferably, the liquid driving means is a pipette. Specifically, the liquid driving device can have the function of accurately measuring the sample liquid, and can provide a liquid driving force to realize the leading-in and leading-out of the sample liquid; the liquid driving device can also have no function of accurately measuring the sample liquid, but can provide liquid driving force to realize the leading-in and leading-out of the sample liquid.
In some embodiments, the sample injection portion 320 includes a sample injection channel 322 and a sample injection port 321, and the sample injection port 321 communicates directly or indirectly with the detection cell 310 through the sample injection channel 322. The sample inlet 321 and the sample channel 322 may allow a driving force output portion of the liquid driving device to be inserted therein and form a seal with the driving force output portion. For example, the liquid driving device is a pipette, the driving force output part is a gun head, and the sample inlet 321 and the sample inlet channel 322 can allow the gun head of the pipette to be inserted into the liquid driving device and form a seal with the gun head.
To achieve the sealing effect, the sample feeding portion 320 may be attached to the driving force output portion of the liquid driving device. Specifically, the inner contour surface of at least part of the section of the sample injection channel can be attached to the outer wall of the driving force output part of the liquid driving device; further, the whole inner contour surface of the sample injection channel can be attached to the outer wall of the driving force output part of the liquid driving device, and the inner contour of the sample injection port can be attached to the outer wall of the driving force output part of the liquid driving device.
In some embodiments, the inner profile of the sample introduction channel 322 is circular. Specifically, for a liquid driving device in which the outer wall of the driving force output portion is a cylindrical surface, the circular tubular inner contour surface of the sample inlet channel 322 may be attached to the outer wall of the driving force output portion of the liquid driving device, which is close to the output port. For example, the outer wall of the injection head of the injector is a cylindrical surface, and the circular tubular inner contour surface of the sample introduction channel 322 can be attached to the outer cylindrical surface of the injection head of the injector close to the injection port.
In some embodiments, as shown in FIG. 4, the inner diameter of the sample channel 322 decreases gradually in the direction from the sample inlet 321 to the detection cell 310. In some embodiments, further, the inner profile of the sample channel 322 is tapered. Specifically, for the liquid driving device with the outer wall of the driving force output part being a conical surface, the sample injection channel 322 with gradually reduced inner caliber can be attached to the outer wall of the driving force output part of the liquid driving device close to the output port especially when the inner contour of the sample injection channel is in a conical shape. For example, the outer wall of the gun head of the liquid transfer device is a conical surface, and the conical tubular inner contour surface of the sample introduction channel 322 can be attached to the outer conical surface of the gun head of the liquid transfer device, which is close to the liquid outlet. Preferably, a sample introduction channel 322 with a tapered tubular inner profile is used.
The length of the sample inlet channel 322 can affect the fit and sealing effect of the sample inlet 320 and the driving force output part of the liquid driving device. It should be noted that, the length of the sample channel 322 refers to the shortest distance of the line on the inner contour surface of the sample channel 322, as shown by the length D in fig. 5. In some embodiments, the length of the sample introduction channel 322 is greater than 1mm.
The position and arrangement of the sample introduction channel 322 can influence the fitting and sealing effect of the sample introduction portion 320 and the driving force output portion of the liquid driving device.
In some embodiments, as shown in fig. 4, a sample inlet 321 and a sample channel 322 may be provided on the first plate body 100. In some embodiments, the sample inlet 321 may be disposed on the first plate 100; the sample introduction channel 322 may be disposed on the first plate 100 and the second plate 200. Specifically, a portion of the sample channel 322 may be formed on the first plate 100, and the remaining portion of the sample channel 322 may be formed on the second plate 200, and the first plate 100 and the second plate 200 are connected to form a complete sample channel 322. In some embodiments, to secure the length of the sample introduction channel 322 and thus improve the sealing effect, the sample introduction channel 322 is obliquely disposed on the first plate 100. Specifically, as shown in fig. 5, the axis of the sample inlet 322 forms an acute included angle θ with the first plate 100 (the surface on which the sample inlet 321 is formed/the upper surface of the substrate). In some embodiments, the included angle θ is preferably 20-60 °.
In some embodiments, as shown in fig. 10, a sample inlet 321 and a sample channel 322 may be disposed between the first plate 100 and the second plate 200. In some embodiments, on the sample inlet 321 opening surface, i.e., on the corresponding sidewall of the substrate opening sample inlet 321, the axis of sample channel 322 may be perpendicular to the sidewall, or the axis of sample channel 322 may be oblique to the sidewall. Specifically, when the sample inlet 321 and the sample channel 322 are disposed between the two plates, the substrate has enough depth in the length and width directions, so that the axis of the sample channel 322 is perpendicular to or inclined to the side wall of the substrate, and the channel length can be enough to meet the sealing requirement.
In some embodiments, as shown in fig. 11, the sample inlet 321 and the sample channel 322 may be disposed on the second plate 200, and on the opening surface of the sample inlet 321, that is, on the corresponding side wall of the substrate where the sample inlet 321 is formed, the axis of the sample channel 322 may be inclined to the side wall.
The sample inlet 321 is arranged in such a way that the fitting and sealing effects of the sample inlet 320 and the driving force output part of the liquid driving device can be affected. In some embodiments, the sample inlet 321 protrudes from the opening surface of the sample inlet 321, so as to ensure the length of the sample channel 322, thereby improving the sealing effect. For example, as shown in fig. 6, the sample channel 322 is obliquely disposed on the first plate body 100, and the sample port 321 protrudes from the first plate body 100 by disposing the flange 323 on the sample portion 320, so as to extend the length of the sample channel 322. For example, as shown in fig. 8, the sample channel 322 is vertically disposed on the first plate 100, and the sample port 321 protrudes from the first plate 100 by providing the flange 323 at the sample portion 320. In some embodiments, the sample inlet 321 preferably protrudes from the first plate 100; the height H of the sample inlet 321 protruding out of the first plate body 100 is 0.5-3mm.
The shape of the sample inlet 321 can influence the fit sealing effect of the sample inlet 320 and the driving force output part of the liquid driving device. In some embodiments, the sample inlet 321 is elliptical on the surface of the sample inlet 321. For example, as shown in fig. 1 and 2, the sample inlet 321 is formed on the first plate body 100 (the upper surface of the substrate), and the sample inlet 321 has an elliptical shape on a cross section parallel to the first plate body 100. Specifically, the sample inlet 321 with an oval cross section may be suitable for a case that the sample inlet 322 is inclined to the opening surface of the sample inlet 321. In some embodiments, the minor axis length of the elliptical sample inlet 321 is between 0.5-4mm on the sample inlet 321 facing surface. In some embodiments, the sample inlet 321 is circular on the surface of the sample inlet 321. For example, the sample inlet 321 is formed on the first plate 100, and the sample inlet 321 is circular in shape on a section parallel to the first plate 100. Specifically, the sample inlet 321 with a circular cross section may be suitable for the case that the sample inlet 322 is perpendicular to the opening surface of the sample inlet 321. In some embodiments, the diameter of the circular cross section of the sample inlet 321 is between 0.5-4mm on the sample inlet 321 opening face.
In some embodiments, the sample introduction portion 320 may also be fitted with and sealed to the driving force output portion of different types of liquid driving devices by providing a detachable elastic seal 324 within the sample introduction channel 322 and/or at the sample introduction port 321. After the driving force output part of the liquid driving device is inserted into the through hole of the elastic sealing element, the inner wall of the through hole of the elastic sealing element deforms to be sealed and attached to the outer wall of the driving force output part, so that the purpose of adapting to the driving force output parts of different types of liquid driving devices is achieved. In some embodiments, the sample introduction portion 320 further includes an elastic sealing member 324, wherein the elastic sealing member 324 is provided with a through hole, and the elastic sealing member 324 is installed in the sample introduction channel 322 and/or on the sample introduction port 321. For example, as shown in fig. 7, an elastic seal 324 is disposed within the sample introduction channel 322; as shown in fig. 8, an elastic sealing member 324 is disposed in the sample introduction channel 322 and the sample introduction port 321; as shown in fig. 9, an elastic sealing member 324 protruding from the first plate body 100 is disposed in the sample introduction channel 322 and on the sample introduction port 321.
Each of the detecting units 300 may have a marker embedded therein. In some embodiments, the markers are pre-embedded in the sample introduction portion 320 and/or the detection cell 310, and at least a portion of the markers are mixed into the sample liquid flowing into and out of the detection cell 310 by the cooperation of the liquid driving device and the sample introduction portion 320. Specifically, by flowing the sample liquid into and out of the detection cell 310, some or all of the markers are mixed into the sample liquid, and a sufficient and uniform mixing effect is achieved.
In some embodiments, the detection unit 300 may further include an exhaust port 330 in communication with the detection cell 310. Specifically, the liquid driving device is connected with the sample feeding portion 320 in a sealing manner, and the air outlet 330 is used for ventilating the detection cell 310 when driving the sample liquid to enter and exit the detection cell 310, so as to balance the gas pressure inside and outside the detection cell 310.
The application also discloses a particle detection device, which is internally provided with a liquid driving device communicated with the detection tank, samples are injected through the liquid driving device, and sample liquid is repeatedly led out and led in from the detection tank. The particle detection apparatus includes a substrate and one or more detection units 300 disposed within the substrate. In some embodiments, each detection unit 300 includes a detection cell 310 capable of containing a sample fluid and a sample introduction portion 320 in communication with the sample introduction cell, wherein the sample introduction portion 320 includes a liquid driving device secured to the substrate, and the liquid driving device is configured to drive at least a portion of the sample fluid into and out of the detection cell 310 repeatedly.
The particle detection device can adopt a negative pressure sample injection mode. Specifically, the liquid driving device is communicated with the detection tank 310 through the corresponding channel, and the liquid driving device forms negative pressure by sucking the gas in the detection tank 310, so that the sample liquid is sucked into the detection tank from the sample inlet communicated with the detection tank 310, and negative pressure sample injection is realized. In some embodiments, the sample injection part 320 further includes a sample injection port 321 and a sample injection channel 322, the sample injection port 321 is communicated with the detection cell 310 through the sample injection channel 322, and the liquid driving device is communicated with the detection cell 310 through the mixing channel 329.
Specifically, as shown in fig. 12, the liquid inlet/outlet amount of the liquid driving device is greater than the liquid storage amount of the detection cell 310, and after the sample inlet 321 is immersed in the sample liquid, the sample liquid can enter the detection cell 310 through the sample inlet channel 322 by the negative pressure provided by the liquid driving device. After the sample liquid in the detection cell 310 reaches a predetermined amount, the sample injection is stopped, the liquid driving device continuously provides negative pressure, so that after part of the sample liquid enters the mixing channel 329, the predetermined amount of positive pressure and negative pressure are periodically provided, the sample liquid flows back and forth between the mixing channel 329 and the detection cell 310, the sample liquid repeatedly enters and exits the detection cell 310, and the liquid flow generated by the sample liquid entering and exiting the detection cell 310 can promote the pre-buried marker in the detection unit 300 to be mixed with the sample liquid.
In some embodiments, the liquid driving device is preferably a plunger pump. In some embodiments, further, the plunger pump includes a plunger 325 and a plunger cavity disposed within the base plate, one end of the plunger 325 extending out of the base plate, the plunger cavity in communication with the detection cell 310 through the mixing channel 329.
In some embodiments, further, a partition flap 327 having elasticity is provided in the plunger chamber, and the partition flap 327 divides the plunger chamber into a first plunger chamber 326a and a second plunger chamber 326b. Further, the first plunger cavity 326a is communicated with the detecting tank 310 through the mixing channel 329, and the liquid inlet amount of the first plunger cavity 326a is greater than or equal to the liquid storage amount of the detecting tank 310. Specifically, in the negative pressure sampling process, when the plunger head contacts the partition valve 327 and senses resistance, sampling can be stopped; continued pumping of the plunger 325 causes the plunger head to enter the second plunger cavity 326b, and reciprocating movement of the plunger 325 within the second plunger cavity 326b causes sample fluid to reciprocate between the detection cell 310 and the first plunger cavity 326a for purposes of thoroughly mixing the sample fluid with the labels.
The particle detection device can also adopt a positive pressure sample injection mode. Specifically, the liquid driving device is communicated with the detection tank 310 through the corresponding channel, and the liquid driving device directly applies positive pressure to the sample liquid to enable the sample liquid to be led into the detection tank, so that positive pressure sample injection is realized. In some embodiments, as shown in fig. 13, the sample injection part 320 further includes a sample injection port 321 and a sample injection channel 322, the liquid driving device is communicated with the detection cell 310 through the mixing channel 329, and the sample injection port 321 is communicated with the detection cell 310 through the sample injection channel 322 and the liquid driving device.
In some embodiments, the liquid driving device is preferably a plunger pump. In some embodiments, further, the plunger pump includes a plunger 325 and a plunger cavity 326 disposed within the base plate, one end of the plunger 325 extending out of the base plate, the plunger cavity 326 being in communication with the test cell 310 through a mixing channel 329. In some embodiments, the sample inlet 321 is formed at an end of the plunger 325 extending out of the substrate, the sample channel 322 is disposed within the plunger 325, and the sample channel 322 communicates with the detection cell 310 through the plunger cavity 326. In some embodiments, it is preferred that the sample inlet 321 be provided with a removable sealing plug 328.
In some embodiments, the detection unit 300 further includes an exhaust port 330 in communication with the detection cell 310. The vent 330 may be used to vent gas to balance the pressure of the gas inside and outside the test cell 310.
Specifically, as shown in fig. 13, the sample injection device may sequentially introduce a sample solution into the detection cell 310 through the sample injection port 321, the sample injection channel 322, the plunger cavity 326, and the mixing channel 329; after sample injection is completed, the sample inlet 321 is plugged, the plunger 325 is pulled to provide liquid driving force, so that sample liquid flows back and forth between the detection cell 310 and the plunger cavity 326, and the sample liquid repeatedly enters and exits the detection cell 310, so that the sample liquid and the marker are fully mixed.
Other structures of the particle detection apparatus are similar to those described above, such as substrate structures, etc., and details may be found in other parts of the disclosure, which are not repeated here.
The application also discloses an operation method of the particle detection device, which can be applied to the particle detection device. According to the operation method, the sample injection part of the particle detection device is connected with the liquid driving device in a sealing way, so that the repeated introduction and the derivation of the sample liquid in the detection tank are realized rapidly. The operation method comprises the following steps:
introducing sample liquid into the detection pool through the sample introduction part;
providing liquid driving force through a liquid driving device which is connected with the sample injection part in a sealing way, so that at least part of the sample liquid repeatedly enters and exits the detection pool;
and driving the sample liquid to flow into the detection cell again through the liquid driving device.
In some embodiments, the liquid drive device drives at least a portion of the sample liquid into and out of the detection cell at least 1 time repeatedly, such that at least a portion of the markers embedded in the detection cell are mixed with the sample liquid. Preferably, the marker is pre-buried in the sample introduction portion and/or the detection cell. Specifically, the liquid driving device can alternately provide positive pressure and negative pressure, and the sealing connection of the liquid driving device and the sample injection part enables the positive pressure and the negative pressure provided by the liquid driving device to effectively act on the sample liquid, so that the sample liquid flows back and forth between the sample injection part and the detection tank, and part or all of the sample liquid repeatedly enters and exits the detection tank for 1 time or more than 1 time, so that the pre-buried marker and the sample liquid can be quickly, fully and uniformly mixed.
In some embodiments, the driving force output part of the liquid driving device is inserted into and presses the sample introduction part, so that the liquid driving device is in sealing connection with the sample introduction part. In some embodiments, the liquid drive device is a device with positive and negative pressure control; wherein, the device with positive and negative pressure control is one of a pipettor, a syringe and a skin-blowing device.
For example, the liquid driving device is a liquid dispenser, and the liquid dispenser can be in sealing connection with the sample introduction part by inserting the gun head of the liquid dispenser into the sample introduction part for compaction; after the sample liquid is introduced into the detection tank by the liquid transfer device, the control button is repeatedly pressed to provide the liquid driving force of alternating positive pressure and negative pressure, so that the sample liquid can repeatedly enter and exit the detection tank, and the purpose of rapid and uniform mixing of the sample liquid and the marker is achieved.
For example, the liquid driving device is a syringe, and the syringe and the sample injection part can be connected in a sealing way by inserting the injection head of the syringe into the sample injection part for compaction; after the sample liquid is introduced into the detection tank by the injector, the plunger rod of the injector is repeatedly pulled to provide a liquid driving force of alternating positive pressure and negative pressure, so that the sample liquid can repeatedly enter and exit the detection tank, and the aim of rapidly and uniformly mixing the sample liquid and the marker is fulfilled.
In some embodiments, the liquid driving device is fixed on the particle detection device, and the liquid driving device is directly or indirectly connected with the sample injection part in a sealing way.
Possible beneficial effects of embodiments of the present application include, but are not limited to: in the prior art, because the depth factor of the detection pond leads to the liquid surface tension in the detection pond big, sample liquid is in case getting into the detection pond, then hardly exports it or aspirates, compares with prior art, the particle detection device of this application makes it can seal cooperation liquid drive arrangement through the structure setting of sampling portion to allow to make sample liquid repetition business turn over detection pond through the cooperation of liquid drive arrangement with sampling portion, carry out the import of sample liquid fast and export. In some application scenarios, for example, when the marker is embedded in the particle detection device, the sealing cooperation of the sample injection part and the liquid driving device enables the sample liquid to repeatedly enter and exit the detection tank, so that the marker and the sample liquid can be mixed rapidly and uniformly. It should be noted that, the advantages that may be generated by different embodiments may be different, and in different embodiments, the advantages that may be generated may be any one or a combination of several of the above, or any other possible advantages that may be obtained.
While the basic concepts have been described above, it will be apparent to those skilled in the art that the foregoing detailed disclosure is by way of example only and is not intended to be limiting. Although not explicitly described herein, various modifications, improvements, and adaptations to the present disclosure may occur to one skilled in the art. Such modifications, improvements, and modifications are intended to be suggested within this specification, and therefore, such modifications, improvements, and modifications are intended to be included within the spirit and scope of the exemplary embodiments of the present invention.
Meanwhile, the specification uses specific words to describe the embodiments of the specification. Reference to "one embodiment," "an embodiment," and/or "some embodiments" means that a particular feature, structure, or characteristic is associated with at least one embodiment of the present description. Thus, it should be emphasized and should be appreciated that two or more references to "an embodiment" or "one embodiment" or "an alternative embodiment" in various positions in this specification are not necessarily referring to the same embodiment. Furthermore, certain features, structures, or characteristics of one or more embodiments of the present description may be combined as suitable.
Claims (17)
1. A particulate detection device comprising a substrate and at least one detection unit disposed on the substrate, the at least one detection unit comprising:
a detection cell, the detection cell being capable of containing a sample fluid;
the sample injection part is communicated with the detection pool and can be in sealing connection with a liquid driving device, and the liquid driving device and the sample injection part are matched to enable the sample liquid to enter and exit the detection pool;
the sample injection part comprises a sample injection channel and a sample injection port communicated with the detection pool through the sample injection channel;
the liquid inlet/outlet amount of the liquid driving device is larger than the liquid storage amount of the detection tank; based on the periodical positive pressure and negative pressure of the liquid driving device, the sample liquid enters and exits the detection pool through the matching of the liquid driving device and the sample injection part;
the sample injection part and/or the detection tank are pre-embedded with markers, and at least part of the markers are mixed into the sample liquid entering and exiting the detection tank through the cooperation of the liquid driving device and the sample injection part.
2. The particulate testing device of claim 1, wherein the internal bore of the sample introduction channel decreases gradually in a direction from the sample introduction port to the test cell.
3. The particulate detection apparatus of claim 2, wherein the inner contour of the sample introduction channel is tapered.
4. The particulate detection device of claim 1, wherein the substrate includes a first plate body and a second plate body; the detection pool is arranged on the second plate body; the sample inlet is arranged on the first plate body; the sample introduction channel is arranged on the first plate body or the sample introduction channel is arranged on the first plate body and the second plate body.
5. The particulate detection apparatus of claim 4, wherein the axis of the sample introduction channel forms an angle of 20-60 ° with the first plate.
6. The particulate detection apparatus of claim 4, wherein the first plate and the second plate are in a sealed arrangement, the detection cell is positioned between the first plate and the second plate, and the sample introduction channel communicates the detection cell with the sample introduction port.
7. The particulate detection apparatus of claim 4, wherein the sample inlet has an elliptical or circular shape in a cross section parallel to the first plate body.
8. The particulate detection apparatus of claim 1, wherein the sample inlet has a minor axis length of from 0.5mm to 4mm.
9. The particulate detection apparatus of claim 4, wherein the sample inlet protrudes from the first plate body.
10. The particulate detection apparatus of claim 9, wherein the sample inlet protrudes from the first plate body to a height of 0.5mm to 3mm.
11. The particulate detection apparatus of any one of claims 1-10, wherein the sample introduction channel has a length greater than 1mm.
12. The particulate detection apparatus of any one of claims 1-10, wherein the sampling portion further comprises an elastic seal, the elastic seal being provided with a through hole, the elastic seal being mounted within the sampling channel and/or on the sampling port.
13. The particulate detection apparatus of any one of claims 1-10, wherein the detection cell has a depth of less than 2mm.
14. A method of operating a particulate detection apparatus according to any one of claims 1 to 13, wherein the method comprises:
introducing sample liquid into the detection pool through the sample introduction part;
providing liquid driving force through a liquid driving device which is connected with the sample injection part in a sealing way, so that at least part of the sample liquid repeatedly enters and exits the detection pool;
and driving the sample liquid to flow into the detection cell again through the liquid driving device.
15. The method of claim 14, wherein the driving force output portion of the liquid driving device is inserted into and presses the sample introduction portion, so that the liquid driving device is hermetically connected to the sample introduction portion.
16. The method of claim 14, wherein the liquid driving means repeatedly drives at least a portion of the sample liquid into and out of the detection cell at least 1 time, so that the sample liquid is mixed with at least a portion of the markers pre-buried in the sample introduction portion and/or the detection cell.
17. The method of operation of claim 14, wherein the liquid drive device is a device having positive and negative pressure control; the device with positive and negative pressure control is one of a pipettor, a syringe and a skin-blowing device.
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| CN202111006391.4A CN113866158B (en) | 2021-08-30 | 2021-08-30 | Particle detection device and operation method thereof |
| US17/823,071 US20230067319A1 (en) | 2021-08-30 | 2022-08-29 | Particle detection device and operation method |
| EP22192830.2A EP4140587A1 (en) | 2021-08-30 | 2022-08-30 | Particle detection device and operation method |
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