CN110508337B - In-vitro detection device and sample loading mechanism thereof - Google Patents
In-vitro detection device and sample loading mechanism thereof Download PDFInfo
- Publication number
- CN110508337B CN110508337B CN201910801439.7A CN201910801439A CN110508337B CN 110508337 B CN110508337 B CN 110508337B CN 201910801439 A CN201910801439 A CN 201910801439A CN 110508337 B CN110508337 B CN 110508337B
- Authority
- CN
- China
- Prior art keywords
- sample
- cavity
- loading
- hole
- sample loading
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
-
- 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
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
-
- 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
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00099—Characterised by type of test elements
- G01N2035/00108—Test strips, e.g. paper
-
- 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
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00099—Characterised by type of test elements
- G01N2035/00158—Elements containing microarrays, i.e. "biochip"
-
- 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
Abstract
The invention discloses an in vitro detection device and a sample loading mechanism thereof. The sample loading mechanism of the in-vitro detection device is provided with a sample loading unit, the sample loading unit comprises a sample loading hole, a sample loading hole and a quantitative cavity with rated volume, the sample loading hole is communicated with the quantitative cavity to be used for adding a sample solution into the quantitative cavity, the sample loading hole is communicated with the quantitative cavity to be used for loading the quantitative sample solution in the quantitative cavity to the detection mechanism, and the sample loading hole is sealed by a water-soluble film. Through setting up the unit of appearance of going up including the ration cavity that has rated capacity, the hole of going up the appearance of unit is sealed by the water-soluble membrane, and the hole of going up the appearance can be delayed time and opened like this, and then after the application of sample, can carry out the ration to the sample solution who adds, need not to use extra application of sample utensil that has the ration function to carry out the ration to sample solution, and easy and simple to handle is favorable to improving detection efficiency to can reduce sample solution's the volume of going up error, be favorable to improving the accuracy of testing result.
Description
Technical Field
The invention relates to the technical field of in-vitro detection, in particular to an in-vitro detection device and a sample loading mechanism thereof.
Background
In Vitro Diagnosis (IVD) refers to a technique for diagnosing diseases by taking samples (blood, body fluid, tissue, etc.) from a human body and performing detection analysis, and corresponding instruments and reagents are required In the detection process, and the instruments and the reagents constitute an In Vitro Diagnosis system. In vitro diagnostic systems are broadly divided into two categories: one is represented by a detection center laboratory, has the characteristics of system modularization and automation, and is used for carrying out pipelined detection on a sample, so that the system also has the advantages of high flux, high efficiency and high sensitivity, but the whole system also has the defects of high cost, large occupied volume, requirement on professional operation and the like, and is mainly applied to large hospitals; in addition, the other method is represented by point-of-care testing (POCT), and the system has the characteristics of integration and miniaturization, can carry out sample testing at any time and any place, and further has the advantages of low price, simplicity in operation and timely result report. However, some conventional in vitro detection devices need to perform sample quantification by means of an additional sample adding device, and particularly for an in vitro detection device with a plurality of sample loading units, the sample loading units are difficult to control simultaneous sample loading, the sample loading consistency is poor, and for some detection occasions requiring simultaneous sample loading control, the detection requirements are difficult to meet.
Disclosure of Invention
In view of the above, it is desirable to provide an in vitro detection apparatus and a loading mechanism thereof, which can quantify a sample and control loading of different loading units simultaneously.
The utility model provides an external detection device's mechanism of getting ready, it is equipped with the unit of getting ready in the appearance mechanism to get ready, the unit of getting ready includes application hole, application hole and has rated capacity's ration cavity, application hole with ration cavity intercommunication in order to be used for to add sample solution in the ration cavity, go up the application hole with ration cavity intercommunication is in order to be used for with quantitative sample solution goes up appearance to detection mechanism in the ration cavity, it is sealed by the water-soluble membrane to go up the application hole.
In one embodiment, the sample loading hole is such that when the water-soluble film is dissolved, the sample solution quantified in the quantification chamber does not automatically flow out of the sample loading hole.
In one embodiment, the radial dimension of the sample loading hole is between 0.5mm and 3 mm.
In one embodiment, the water-soluble film is a water-soluble film which dissolves in 5 s-120 s of water.
In one embodiment, the sample loading mechanism is provided with a plurality of sample loading units, and the plurality of sample loading units are arranged on the sample loading mechanism around a rotation center.
In one embodiment, the loading hole of each loading unit is located farther from the rotation center than the loading hole on the loading mechanism.
In one embodiment, the sample loading mechanism is a microfluidic chip, and the sample loading unit further comprises a sample loading cavity;
the sample adding hole is communicated with the sample adding cavity and is used for adding a sample solution into the sample adding cavity;
the sample adding cavity is communicated with the quantitative cavity through a capillary flow channel.
In one embodiment, the sample loading unit further comprises a waste liquid cavity;
the waste liquid cavity is communicated with the sample adding cavity or the quantitative cavity, and the waste liquid cavity is positioned at the downstream of the quantitative cavity along the flowing direction of the sample solution.
An in vitro detection device comprises a detection mechanism and the sample loading mechanism of any one of the embodiments, wherein a sample inlet of the detection mechanism is opposite to a sample loading hole of a sample loading unit, and the sample inlet is separated from the sample loading hole by a water-soluble film.
In one embodiment, the detection mechanism is a detection test paper, and the end of the detection test paper where the sample inlet is located is adhered to the sample loading mechanism.
Above-mentioned external detection device and mechanism of getting ready thereof, through setting up the unit of getting ready including the ration cavity that has rated capacity, the hole of getting ready of the unit of getting ready is sealed by the water-soluble membrane, the hole of getting ready like this can delay and open, and then after the application of sample, can quantify the sample solution of adding, need not to use extra application of sample utensil that has the ration function to quantify the sample solution, and is easy and simple to handle, be favorable to improving detection efficiency, and can reduce sample solution's the volume error of getting ready, be favorable to improving the accuracy of testing result.
Furthermore, when the sample loading mechanism is provided with a plurality of sample loading units, the delayed opening function of the water-soluble film for closing the sample loading holes can be fully utilized, and particularly, the structure design of the sample loading holes can be further matched, so that the sample solution can not automatically flow out after the water-soluble film is dissolved, and the simultaneous sample loading of different sample loading units on the detection mechanism can be realized by means of centrifugation or vibration and the like, thereby being beneficial to fully ensuring the time consistency of sample loading of each sample loading unit.
Drawings
FIG. 1 is a schematic view of a modular structure design of a sample loading mechanism provided by the present invention;
FIG. 2 is a schematic front view of a loading mechanism of a microfluidic chip according to an embodiment;
FIG. 3 is a schematic view of the back side of the loading mechanism of FIG. 2;
FIG. 4 is a side view of the loading mechanism engagement detection mechanism shown in FIG. 2;
FIGS. 5-1, 5-2, 5-3 and 5-4 are schematic views illustrating a process of plasma (or serum) separation and quantification of a whole blood sample by the loading mechanism shown in FIG. 2, and FIGS. 5-2-1, 5-3-1 and 5-4-1 are corresponding enlarged partial schematic views;
FIGS. 6-1, 6-2 and 6-3 are schematic diagrams of the process of dissolving a water-soluble film into plasma (or serum) and entering a detection mechanism;
FIG. 7 is a schematic diagram of a dry chemical test strip in one embodiment.
Detailed Description
To facilitate an understanding of the invention, the invention will now be described more fully hereinafter with reference to the accompanying drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
It will be understood that when an element is referred to as being "secured to" another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" or "coupled" to another element, it can be directly connected or coupled to the other element or intervening elements may also be present.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
As shown in fig. 1, the present invention provides a loading mechanism 1 of an in vitro test device. The sample loading mechanism 1 is provided with a sample loading unit 2. The loading unit 2 comprises a loading hole 3, a loading hole 4 and a quantitative cavity 5 with rated volume. The sample adding hole 3 is communicated with the quantitative cavity 5 for adding a sample solution into the quantitative cavity 5. The sample loading hole 4 is communicated with the quantitative cavity 5 so as to load the quantitative sample solution in the quantitative cavity 5 to the detection mechanism for detection. The loading hole 4 is closed by a water-soluble film 6.
Preferably, the sample loading hole 4 is configured such that, after the water-soluble film 6 is dissolved, the sample solution quantified in the quantification cavity 5 does not automatically flow out from the sample loading hole, which is beneficial to ensuring the accuracy of sample loading and quantification and the consistency of subsequent sample loading time. It is further preferred that the loading well 4 has a radial dimension (the largest dimension of the cross-section of the well, such as the diameter of a circular well, i.e. the diameter, and such as the length of a rectangular well and its diagonal) of between 0.5mm and 3 mm.
The water-soluble film 6 is slowly dissolved in water. Preferably, the water-soluble film 6 used in the invention is a water-soluble film which dissolves in 5 s-120 s of water, so that sufficient delay time can be reserved for the sample adding process, and the accuracy of sample adding quantification is ensured. The water-soluble film 6 may be, but is not limited to, a PVA (polyvinyl alcohol) film.
Preferably, the sample loading mechanism 1 is provided with a plurality of sample loading units 2. A plurality of loading units 2 are arranged on the loading mechanism 1 around a rotation center. After the sample solution is added into the quantitative cavity 5, the sample solution in the quantitative cavity 5 can be completely discharged through centrifugation and other manners, so that the accuracy and consistency of the sample loading amount of each sample loading unit 2 can be ensured.
Preferably, in the loading mechanism 1, the loading hole 4 of each loading unit 2 is arranged far away from the rotation center than the loading hole 3, so that during centrifugal loading, the situation that the sample solution flows back to the loading hole 3 can be avoided, and the accuracy of the loading amount is further ensured.
The sample loading mechanism 1 is preferably a microfluidic chip, and the sample loading unit 2 further comprises a sample loading cavity 7. The sample adding hole 3 is communicated with the sample adding cavity 7 and is used for adding a sample solution into the sample adding cavity 7. The sample adding cavity 7 is communicated with the quantitative cavity 6 through a capillary flow channel 8. Through setting up capillary flow channel 8, can be with adding the sample solution in application of sample cavity 7 through capillary action automatic flow to quantitative cavity 6 in the ration realization application of sample volume, and the sample solution that adds in application of sample cavity 7 can be a little excessive, can improve the simplicity and convenience of operation.
Preferably, the loading unit 2 further comprises a waste liquid chamber 9. The waste liquid cavity 9 is communicated with the sample adding cavity 7 or the quantitative cavity 6. The waste liquid chamber 9 is located downstream of the quantification chamber 6 in the direction of flow of the sample solution. Through set up waste liquid cavity 9 in the low reaches of ration cavity 6, can be used for accurately judging whether fill up sample solution in the ration cavity 6, when the sample solution appears in the waste liquid cavity 9 that is located the low reaches, can judge that fill up sample solution in the ration cavity 6. Through setting up waste liquid cavity 9, can provide clear and definite instruction for the application of sample of ration cavity 5, further be favorable to improving the convenience of operation.
Further preferably, the waste liquid cavity 9 may be provided with air holes to discharge air in each cavity and pipeline in time, so as to ensure smooth flow of the sample solution. The air hole can be arranged on the waste liquid cavity 9, and also can be arranged at the tail end of a micro-channel communicated with the waste liquid cavity 9 and other positions.
The invention also provides an in-vitro detection device which comprises the sample loading mechanism 1 and a detection mechanism. The sample inlet of the detection mechanism is opposite to the sample loading hole 4 of the sample loading unit 2, and the sample inlet is separated from the sample loading hole 4 by a water-soluble film 6.
The detection mechanism may be, but is not limited to, a test strip. Preferably, the end of the test paper where the sample inlet is located is adhered to the sample loading mechanism 1.
Above-mentioned in vitro detection device and mechanism 1 that samples thereof, through setting up the unit 2 that samples of the ration cavity 5 that has rated volume, the hole 4 that samples of the unit 2 that samples is sealed by water-soluble membrane 6, it can open by the time delay like this to go up the hole, and then after the application of sample, can quantify the sample solution of adding, need not to use extra application of sample utensil that has the ration function to quantify sample solution, and is easy and simple to handle, and the detection efficiency can be improved, and can reduce sample solution's the error of the volume of samples of going up, the accuracy that is favorable to improving the testing result.
When the sample loading mechanism 1 is provided with a plurality of sample loading units 2, the delayed opening function of the water-soluble film 6 for closing the sample loading holes 4 can be fully utilized, and particularly, the structure design of the sample loading holes 4 can be further matched, so that the sample solution can not automatically flow out after the water-soluble film 6 is dissolved, and the simultaneous sample loading of different sample loading units 2 on the detection mechanism can be realized by means of centrifugation or vibration and the like, thereby being beneficial to fully ensuring the time consistency of sample loading of each sample loading unit 2.
The structure of the in vitro testing device and the loading mechanism thereof will be further described in detail below with reference to an embodiment of the in vitro testing device consisting of the loading mechanism of a specific microfluidic chip and the testing mechanism matched with the loading mechanism. In the following examples, the microfluidic chip corresponds to the sample loading mechanism.
Referring to fig. 2 and 3, a separation and quantification unit 100 is disposed on the microfluidic chip 10 according to an embodiment. The separation and quantification unit 100 includes a sample application chamber 110, a first microchannel 120, a precipitation chamber 130, a capillary channel 140, a second microchannel 150, and a quantification chamber 160. The sample adding cavity 110 is used for containing a sample solution to be detected, and is provided with a sample adding hole 111. The sedimentation chamber 130 is used for collecting useless matters in the solid sample to be measured with high density. The sample application chamber 110 is communicated with the precipitation chamber 130 through the first microchannel 120. The first microchannel 120 is in communication with the second microchannel 150 via the capillary channel 140. The second microchannel 150 is in communication with the dosing chamber 160. The quantitative cavity 160 is used for quantifying the sample solution to be measured.
In this embodiment, the microfluidic chip 10 has a center of rotation 18. The precipitation chamber 130 is further from the center of rotation 18 than the sample application chamber 110. The capillary flow channel 140 extends from the direction of connection with the first microchannel 120 toward the center of rotation 18 (may be a direction each gradually approaching the center of rotation 18, such as but not limited to a radial direction) and curves to extend toward the direction away from the center of rotation 18 (may be a direction each gradually departing from the center of rotation 18, such as but not limited to a radial direction) to connect with the second microchannel 150. The quantitative cavity 160 is located farther from the center of rotation than the capillary flow path 140.
In the illustrated embodiment, the bottom of the end of the sample application chamber 110 connected to the first microchannel 120 is inclined so that the sample to be measured flows into the first microchannel 120.
The first microchannel 120 is sized to allow the passage of the relatively dense unwanted substances in the sample, for example, in the case of a whole blood sample, when separating plasma or serum, the first microchannel 120 is sized to allow the passage of blood cells in the whole blood. In the illustrated specific example, the first microchannel 120 has a branch portion 121 extending in a direction close to the rotation center 18, and the capillary channel 140 is connected to the end of the branch portion 121 of the first microchannel 120.
Preferably, the separation dosing unit 100 further comprises a waste liquid chamber 170. The waste liquid chamber 170 is used for collecting the excess solution to be tested. The waste chamber 170 is in communication with the second microchannel 150. The waste chamber 170 is located downstream of the quantification chamber 160 on the second microchannel 150 to receive excess solution to be tested. The waste chamber 170 is further from the center of rotation 18 than the capillary flow channel 140. When the solution to be measured appears in the waste liquid cavity 170, it indicates that the quantitative cavity 160 located at the upstream of the waste liquid cavity is filled with the solution to be measured, so that the quantitative cavity 160 can quantify the solution to be measured.
Preferably, the sample-adding cavity 110 is further provided with a first vent 112. The first air hole 112 is used for ventilation, so that the sample can be conveniently added, and the influence on the sample entering caused by the rise of the air pressure in the cavity during sample adding is avoided.
Preferably, a flow blocking plate 113 is disposed between the sample adding hole 111 and the first air hole 112 in the sample adding cavity 110. The flow blocking plate 113 may serve to block the sample from reaching one side of the first vent 112 after the sample is added, and prevent the sample from flowing out of the first vent 112.
Preferably, the sample application hole 111 and the first air vent 112 are disposed near the rotation center 18 on the sample application cavity 110, so that when the sample flows to the side of the sample application cavity 110 away from the rotation center by rotating centrifugation, the sample can be placed to flow out from the sample application hole 111 and the first air vent 112, and the sample can flow into the first microchannel 120 and the sedimentation cavity 130 smoothly.
The capillary flow passage 140 has a V-shape with a curved portion near the rotation center 18. Preferably, the width of the capillary flow channel 140 is 0.1mm to 0.2mm, and the depth is 0.1mm to 0.2 mm; or the width of the capillary flow channel 140 is 0.2 mm-0.5 mm, and the depth is 0.2 mm-0.5 mm. When the width of the capillary flow channel 140 is 0.1mm to 0.2mm and the depth is 0.1mm to 0.2mm, the flow channel wall of the capillary flow channel 140 does not need to be surface-treated, and when the width of the capillary flow channel 140 is 0.2mm to 0.5mm and the depth is 0.2mm to 0.5mm, the flow channel wall of the capillary flow channel 140 is preferably surface-treated with PEG 4000. Further preferably, the capillary flow channel 140 has a width of 0.2mm and a depth of 0.2 mm. After the sample solution enters the capillary channel 140, the sample solution can flow to the other end of the capillary channel by capillary action, and finally a siphon action is formed between the first micro flow channel 120 and the second micro flow channel 150.
The PEG4000 surface treatment may be, but is not limited to, adding a 1 wt% PEG4000 solution to the capillary flow channel 140, and naturally drying the solution to form the PEG4000 surface treatment. The PEG4000 surface treatment is beneficial to increasing the capillary force of the capillary flow channel 140, and the PEG4000 belongs to an inert substance in a reaction system and generally does not react with a sample, a detection reagent and the like, so that the detection result is not influenced.
Preferably, the second micro flow channel 150 is provided with a second vent 151. The second vent 151 is located downstream of the cavity structures (e.g., the dosing cavity 160 and the waste cavity 170) connected to the second microchannel 150, and the second vent 151 is closer to the center of rotation 18 than the cavity structures connected to the second microchannel 150. The second vent 151 also serves as a vent, so that the sample solution to be measured can flow into the second micro flow channel 150 smoothly and finally flow into the quantitative cavity 160 and the waste liquid cavity 170.
It is understood that in other embodiments, the first vent 112 and the second vent 151 may be selected alternatively, for example, only the first vent 112 may be selected alternatively, or only the second vent 151 may be selected alternatively, wherein the second vent 151 is preferably selected alternatively.
Further, the portion of the second microchannel 150 located at the downstream of the connected cavity structure bends and extends toward the direction close to the rotation center 18, and the second vent 151 is disposed at the end of the second microchannel 150, so that the sample solution can be effectively prevented from flowing out of the second vent 151.
Preferably, referring to fig. 4, the microfluidic chip 10 includes a chip body 11 and a transparent cover film 12 covering the chip body 11. The chip body 11 and the transparent cover film 12 cooperate to form each cavity structure and flow channel structure of the separation quantifying unit 100. Specifically, the grooves and the like of each cavity structure and the flow channel structure are preformed on the chip body 11, as shown in fig. 3, each hole is opened on the back surface of the chip body, and the cavity structure and the flow channel structure can be packaged by covering and sealing the transparent cover film 12 on the front surface of the chip body 11, so that a complete cavity structure and a complete flow channel structure are formed.
The transparent cover film 12 can be, but is not limited to, a transparent adhesive tape or a transparent pressure-sensitive adhesive, and the like, and is matched with the chip body 11 to form the whole microfluidic chip 10, so that the assembly is simple, a complex and expensive ultrasonic welding technology is not required, the direct bonding is only required, and the manufacturing cost can be obviously reduced. It is understood that in other specific examples, the microfluidic chip 10 may be formed by welding using a costly ultrasonic welding technique or integrally formed by using a 3D printing technique.
Preferably, there are a plurality of separate dosing units 100, and the plurality of separate dosing units 100 are arranged around the same centre of rotation 18. Through setting up a plurality of quantitative unit 100 can realize that the multiple sample is single to be detected, also can realize that the single sample is multinomial to detect, the uniformity is good, and the integrated level is high, is showing the flux that has improved single and detect.
Preferably, for example, in the illustrated specific example, the microfluidic chip 10 has a disk shape, the plurality of discrete quantitative units 100 are uniformly distributed on the microfluidic chip 10, the middle of the microfluidic chip 10 has a rotation mounting part 180, and the center of the rotation mounting part 180 is the rotation center 18. The rotation mounting part 180 may be various types of slots or posts.
The microfluidic chip 10 of this embodiment is provided with a sample adding cavity 110, a precipitation cavity 130, and a quantitative cavity 160, a sample to be tested can be added into the sample adding cavity 110 through the sample adding hole 111, a solid precipitate can be separated from a liquid through centrifugal separation, to obtain a solution to be tested containing a target substance, the solution to be tested in the sample adding cavity 110 and the first micro flow channel 120 can drive the liquid to flow through a capillary force of the capillary flow channel 140, and finally, a siphon effect and an external centrifugal effect are formed to flow into the quantitative cavity 160, so as to quantify the solution to be tested. The microfluidic chip 10 of the embodiment has a relatively simple structure, is easy to manufacture and mold, and can be widely popularized and used.
Referring to fig. 3, 4, 6-1, 6-2 and 6-3, the present embodiment further provides an in vitro detection apparatus, which includes the above microfluidic chip 10 and the detection mechanism 20. The detection mechanism 20 is used for detecting the sample in the quantitative cavity 160 of the microfluidic chip 10.
In the particular example illustrated, the detection mechanism 20 is external. Specifically, the quantitative cavity 160 has a loading hole 161, and the loading hole 161 is covered with a water-soluble film 162. The sample inlet 21 of the detection mechanism 20 is abutted to the sample loading hole 161 and separated by a water-soluble film 162.
In one particular example, the detection mechanism 20 is a dry chemical strip. As shown in fig. 7, the dry chemical test paper 20 includes a support layer 22, and a reaction indicating layer 23 and a diffusion layer 24 sequentially stacked on the support layer 22. The reaction indicator layer 23 contains a reaction reagent and an indicator reagent that can react with a target substance in a sample to be measured. The reaction indicating layer 23 may be one layer or a plurality of layers, for example, in the specific example shown in fig. 7, the reaction indicating layer 23 includes two layers, i.e., an indicating layer 231 and a reagent layer 232, the indicating layer 231 is adjacent to the support layer 22 and contains a color-developing indicating reagent, and the reagent layer 232 is adjacent to the diffusion layer 24 and contains a reaction reagent capable of reacting with the target substance; further, the reagents contained in the indicator layer 232 and the reagent layer 232 may be exchanged or appropriately mixed. The diffusion layer 24 faces the water-soluble film 162 through the injection port 21.
Further, the microfluidic chip 10 is provided with a mounting groove around the loading hole. The detection mechanism 20 is embedded in the mounting groove.
The in vitro detection device is provided with the detection mechanism 20, can directly detect quantitative sample solution to be detected in the quantitative cavity 160, and has simple operation and high detection efficiency. Taking the whole blood sample loading test as an example, the specific test process of the in vitro test device using the dry chemical test paper can be referred to as follows:
referring to fig. 5-1, 5-2, 5-3 and 5-4, a certain amount of whole blood is added into the sample-adding cavity 110 through the sample-adding hole 111, and six different samples can be sequentially added;
after the sample is added, the rotary mounting part 180 of the in-vitro detection device is mounted in a matched rotary centrifugal instrument, the instrument is started to rotate, red blood cells and the like are precipitated in the precipitation cavity 130 under the action of centrifugal force, and serum or plasma is separated to the upper part of the precipitation cavity 130, the second micro-channel 120 and the sample adding cavity 110;
when the microfluidic chip 10 rotates, serum or plasma is only partially filled in the capillary flow channel 140, as shown in fig. 5-2-1 and 5-3-1, and the liquid level thereof exceeds the inlet end 140a of the capillary flow channel 140 and does not exceed the bending part 140b of the capillary flow channel 140; when the microfluidic chip 10 stops rotating, under the capillary force of the capillary flow channel 140, the serum or plasma crosses the bending part 140b and reaches the end 140c of the capillary flow channel 140, and because the point of the end 140c is lower than the liquid level height in the sample application cavity 110 (the liquid level in the sample application cavity 110 is far away from the rotation center 18), a siphon action can be formed;
when the capillary channel 140 is filled with serum or plasma, the microfluidic chip 10 is controlled to rotate again, because the end 140c is far away from the rotation center 18 than the liquid level in the sample-adding cavity 110, as shown in fig. 5-3-1 and 5-4-1, under the action of siphon and centrifugal force, the serum or plasma enters the quantitative cavity 160 through the second micro-channel 150, when the quantitative cavity 160 is filled with serum or plasma, the quantification of the sample solution to be detected is completed, and the excess serum or plasma enters the rear section of the second micro-channel 150 or enters the waste liquid cavity 170; preferably, the instrument will determine whether the quantitative cavity 160 is full of liquid according to whether liquid is present in the rear section of the second microchannel 150 or the waste liquid cavity 170, and when liquid is present in the rear section of the second microchannel 150 or the waste liquid cavity 170, it can be determined that the quantitative cavity 160 is full of liquid, otherwise, it is alerted to detect whether the quantitative cavity 160 is full of liquid again;
starting to rotate when the capillary channel 140 is filled with serum or plasma until the quantitative cavity 160 is filled with liquid, the operation can be completed within 10s generally, when the quantitative cavity 160 is filled with liquid, controlling the microfluidic chip 10 to stop rotating, standing, temporarily sealing the liquid in the quantitative cavity 160, and gradually dissolving the water-soluble film 162 covered at the sample loading hole 161 with the passage of time, wherein the dissolving process takes about 1min, as shown in fig. 6-1, 6-2 and 6-3;
when the water-soluble film 162 is dissolved, the liquid will not flow into the detection mechanism (dry chemical test paper) 20 due to its own weight, and the micro-fluidic chip 10 needs to be controlled to rotate at a low speed of 1800rpm to 2000rpm, so that the quantitative sample solution in the quantitative cavity 160 enters the sample inlet 21 of the detection mechanism 20;
the sample solution is diffused to the reaction indication layer 23 through the diffusion layer 24 in sequence to carry out color reaction, the concentration of the detection object can be reflected by the depth of color development, signal acquisition can be carried out through the detection hole 25 of the detection mechanism, and finally the concentration data of the detection object is converted. The in vitro detection device of the embodiment can solve the problems of low sensitivity and low stability of the dry chemical test paper whole blood, and has the advantages of high detection flux, low cost and the like.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that various changes and modifications can be made by those skilled in the art without departing from the spirit of the invention, and these changes and modifications are all within the scope of the invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (8)
1. The sample loading mechanism of the in-vitro detection device is characterized in that a sample loading unit is arranged on the sample loading mechanism, the sample loading unit comprises a sample loading hole, a sample loading hole and a quantitative cavity with a rated volume, the sample loading hole is communicated with the quantitative cavity to be used for adding a sample solution into the quantitative cavity, the sample loading hole is communicated with the quantitative cavity to be used for loading the quantitative sample solution in the quantitative cavity to the detection mechanism, and the sample loading hole is sealed by a water-soluble film;
the sample loading mechanism is a microfluidic chip, and the sample loading unit further comprises a sample loading cavity;
the sample adding hole is communicated with the sample adding cavity and is used for adding a sample solution into the sample adding cavity;
the bottom of the sample adding cavity close to the capillary flow channel is obliquely arranged, the sample adding cavity is also provided with a first air vent, and a spoiler is arranged between the sample adding hole and the first air vent;
the sample adding cavity is communicated with the quantitative cavity through a capillary flow channel;
the width of the capillary flow channel is 0.1 mm-0.2 mm, the depth is 0.1 mm-0.2 mm, and the flow channel wall of the capillary flow channel is not subjected to surface modification treatment; or the width of the capillary flow channel is 0.2 mm-0.5 mm, the depth is 0.2 mm-0.5 mm, and the flow channel wall of the capillary flow channel is subjected to PEG4000 surface treatment;
the sample adding hole and the first air hole are arranged on one side of the sample adding cavity far away from the capillary flow channel;
the sample loading hole meets the condition that after the water-soluble film is dissolved, the quantitative sample solution in the quantitative cavity can not automatically flow out of the sample loading hole.
2. The loading mechanism of the in vitro test device according to claim 1, wherein the radial dimension of the loading hole is between 0.5mm and 3 mm.
3. The loading mechanism of in-vitro detecting device according to claim 1, wherein the water-soluble film is a water-soluble film which dissolves in 5 s-120 s of water.
4. The in vitro detection device sample loading mechanism according to any one of claims 1 to 3, wherein a plurality of sample loading units are arranged on the sample loading mechanism, and the plurality of sample loading units are arranged on the sample loading mechanism around a rotation center.
5. The loading mechanism of the in-vitro detection device according to claim 4, wherein the loading hole of each loading unit is arranged farther from the rotation center than the loading hole on the loading mechanism.
6. The loading mechanism of the in vitro test device according to claim 1, wherein the loading unit further comprises a waste liquid chamber;
the waste liquid cavity is communicated with the sample adding cavity or the quantitative cavity, and the waste liquid cavity is positioned at the downstream of the quantitative cavity along the flow direction of the sample solution.
7. An in vitro detection device, comprising a detection mechanism and the sample loading mechanism according to any one of claims 1 to 6, wherein a sample inlet of the detection mechanism is opposite to a sample loading hole of the sample loading unit, and the sample inlet and the sample loading hole are separated by the water-soluble film.
8. The in vitro test device according to claim 7, wherein the test mechanism is a test strip, and the end of the test strip where the sample inlet is located is adhered to the sample loading mechanism.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2019/122797 WO2020192169A1 (en) | 2019-03-27 | 2019-12-03 | In vitro detection device and sample loading mechanism thereof |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201920399948 | 2019-03-27 | ||
| CN2019203999487 | 2019-03-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110508337A CN110508337A (en) | 2019-11-29 |
| CN110508337B true CN110508337B (en) | 2022-08-30 |
Family
ID=68628708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910801439.7A Active CN110508337B (en) | 2019-03-27 | 2019-08-28 | In-vitro detection device and sample loading mechanism thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN110508337B (en) |
| WO (1) | WO2020192169A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110508337B (en) * | 2019-03-27 | 2022-08-30 | 广州万孚生物技术股份有限公司 | In-vitro detection device and sample loading mechanism thereof |
| CN113663747A (en) * | 2021-07-30 | 2021-11-19 | 浙大城市学院 | High-dynamic-range multiple digital PCR chip and preparation method thereof |
| CN116237102A (en) * | 2023-05-11 | 2023-06-09 | 杭州博日科技股份有限公司 | Microfluidic chip |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU741672B2 (en) * | 1997-09-16 | 2001-12-06 | Sekisui Chemical Co., Ltd. | Blood test container and blood test method |
| DE202004014908U1 (en) * | 2004-07-15 | 2005-03-17 | Levin Felix | Rapid analysis system, to detect and identify substances in a fluid, e.g. urine, comprises a suction vessel combined with one or more reagents which dissolve rapidly to give specific visual reactions |
| JP5161218B2 (en) * | 2006-08-02 | 2013-03-13 | サムスン エレクトロニクス カンパニー リミテッド | Thin film chemical analyzer and analysis method using the same |
| US8835157B2 (en) * | 2007-04-25 | 2014-09-16 | 3M Innovative Properties Company | Supported reagents, methods, and devices |
| CN101850231B (en) * | 2009-07-03 | 2012-08-29 | 中国科学院上海微系统与信息技术研究所 | Micro-fluid reactor, using method and application thereof |
| CN202369443U (en) * | 2011-10-20 | 2012-08-08 | 河海大学 | Anaerobic, hypoxic and aerobic SBR |
| CN103464230B (en) * | 2013-09-25 | 2015-02-18 | 中国科学院长春光学精密机械与物理研究所 | Centrifugal whole blood analysis micro-fluidic chip, preparation method as well as application method thereof |
| CN103486091B (en) * | 2013-09-25 | 2016-08-17 | 中国科学院长春光学精密机械与物理研究所 | The siphon valve of centrifugal type microfludic chip and application process thereof |
| EP3052234A2 (en) * | 2013-09-30 | 2016-08-10 | Göran Stemme | A microfluidic device, use and methods |
| TWI550274B (en) * | 2014-08-20 | 2016-09-21 | 紹興普施康生物科技有限公司 | Microfluidics based analyzer and method for operation thereof |
| CN104360091B (en) * | 2014-11-21 | 2016-08-24 | 博奥生物集团有限公司 | A kind of chip, using method and purposes |
| CN104793004A (en) * | 2015-04-24 | 2015-07-22 | 杭州霆科生物科技有限公司 | Pesticide residue detection micro-fluidic chip with pre-stored reaction reagent |
| CN105728070A (en) * | 2015-12-17 | 2016-07-06 | 广州万孚生物技术股份有限公司 | Carrier used for micro-fluidic chip |
| CN206229376U (en) * | 2016-01-22 | 2017-06-09 | 上海快灵生物科技有限公司 | A kind of centrifugal multi-channel fluid chip |
| CN107058063B (en) * | 2017-06-12 | 2019-08-20 | 博奥生物集团有限公司 | A method of the fluorescence detection of multiple nucleic acid amplified production is used for based on micro-fluidic chip |
| CN107051305B (en) * | 2017-06-26 | 2023-03-03 | 浙江普施康生物科技有限公司 | Microfluidic hemagglutination detection device and method |
| CN208104419U (en) * | 2017-12-29 | 2018-11-16 | 苏州绘真生物科技有限公司 | Detect the micro-fluidic chip and detection system of human virus' nucleic acid |
| CN207786626U (en) * | 2018-01-11 | 2018-08-31 | 郑州大学 | A kind of centrifugal type microfludic chip for the multi-joint inspection of vaginitis |
| CN208266181U (en) * | 2018-01-23 | 2018-12-21 | 上海速创诊断产品有限公司 | A kind of nucleic acid analyzer for constant temperature micro-fluidic chip |
| CN108872558B (en) * | 2018-04-26 | 2020-03-31 | 烟台芥子生物技术有限公司 | Method for performing chemical reaction using dissolvable film and detection kit comprising dissolvable film |
| CN108704677A (en) * | 2018-04-27 | 2018-10-26 | 广州万孚生物技术股份有限公司 | A kind of micro-fluidic chip and the analytical instrument containing it |
| CN110508337B (en) * | 2019-03-27 | 2022-08-30 | 广州万孚生物技术股份有限公司 | In-vitro detection device and sample loading mechanism thereof |
-
2019
- 2019-08-28 CN CN201910801439.7A patent/CN110508337B/en active Active
- 2019-12-03 WO PCT/CN2019/122797 patent/WO2020192169A1/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| WO2020192169A1 (en) | 2020-10-01 |
| CN110508337A (en) | 2019-11-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2020192168A1 (en) | Microfluidic chip and in vitro testing device containing the microfluidic chip | |
| CN210787394U (en) | Micro-fluidic chip and in-vitro detection device comprising same | |
| CN110508337B (en) | In-vitro detection device and sample loading mechanism thereof | |
| CN110586209A (en) | Micro-fluidic chip and in-vitro detection device comprising same | |
| KR101930610B1 (en) | Rotatable cartridge for analyzing a biological sample | |
| WO2021243882A1 (en) | Microfluidic chip and in-vitro detection apparatus | |
| CN110975951A (en) | Micro-fluidic chip and in-vitro detection device | |
| EP2563901A1 (en) | Sample analysis system and method of use | |
| CN111551706B (en) | Disc-type immunodetection method for one-time sample-adding multi-item joint inspection | |
| CN108051393B (en) | Full-automatic urine detection device and intelligent closestool using same | |
| CN115254220B (en) | Microfluidic chip and detection method | |
| WO2021077591A1 (en) | Microfluidic chip and in vitro test system | |
| WO2021077590A1 (en) | Microfluidic control chip and in vitro detection apparatus | |
| CN210787395U (en) | Micro-fluidic chip and in-vitro detection device containing same | |
| WO2006038682A1 (en) | Solid-liquid separation/measuring structure and method of solid-liquid separation/measuring | |
| EP3493908B1 (en) | Device and method for liquid analysis to detect biomarkers | |
| CN114414823A (en) | Biochemical project detection disc | |
| US20230142816A1 (en) | Microfluidic point-of-care assay | |
| US11933701B2 (en) | Devices and methods for sample analysis with serial dilution | |
| CN211865061U (en) | Micro-fluidic chip and in-vitro detection device | |
| CN211865063U (en) | Micro-fluidic chip and in-vitro detection device | |
| CN114453037B (en) | Homogeneous phase test micro-fluidic chip and detection system | |
| CN218834551U (en) | Micro-fluidic chip with compact structure | |
| CN217212766U (en) | Biochemical project detection disc | |
| CN211865064U (en) | Micro-fluidic chip |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |