CN210965157U - Integrated biological sample detection chip - Google Patents
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- CN210965157U CN210965157U CN201921245270.3U CN201921245270U CN210965157U CN 210965157 U CN210965157 U CN 210965157U CN 201921245270 U CN201921245270 U CN 201921245270U CN 210965157 U CN210965157 U CN 210965157U
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Abstract
The utility model discloses an integrated biological sample detection chip, which comprises at least one sample adding hole for adding a sample to be analyzed; at least one reaction cell; at least two reagent reservoirs; the sample adding hole is connected with the reaction tank through a flow path, and the reagent liquid storage tank is connected with the reaction tank through a flow path; the flow path is provided with at least one controllable valve for controlling the flow switch of the reagent in the reagent storage tank to the reaction tank; the flow path is provided with at least one controllable valve for controlling the liquid discharge switch of the reagent reaction tank; at least one magnetic material or a magnetic control material which has interaction force with the magnetic material is arranged in the valve cavity and is used as a moving element, and the flow path is opened and closed under the action of the magnetic force; the reaction time of the liquid on the chip can be accurately controlled under an external magnetic field, and the convenience and the accuracy of liquid mobilization control are ensured, so that the control of the chip on the biological detection reaction condition is greatly improved.
Description
Technical Field
The utility model relates to a detect chip technical field, concretely relates to integrated biological sample that can accurately carry out reaction control detects chip.
Background
Poct (point of care testing), which is a clinical test performed beside a patient and is commonly called "point of care testing", has been developed, and a simple method and a miniaturized instrument are generally adopted to rapidly obtain a test result. The concept of clinical inspection POCT is clearly proposed by American AACC in 1995, the POCT is rapidly developed in nearly 20 years, the market scale of the POCT in 2013 worldwide reaches $ 160 billion, the market scale of the POCT in China reaches 80 billion RMB in 2015, and the annual composite growth of the POCT in China exceeds 20%. The detection of POCT is mainly used for analyzing and detecting biological samples, including biological components in samples such as blood, saliva, urine, semen, secretion, body fluid and the like.
The automation equipment and products of large-scale manufacturers are developed rapidly, the reliability is improved rapidly, reagents, reaction technologies and reliability reach high levels, high-end products of enterprises such as Roche, Yapei, Xismemcang, Qiangsheng and Mirui are applied well in the market, products of the enterprises are high-degree automation and systematicness products, and the system has high accuracy and precision through unified quality control and calibration and maintenance, but the system is expensive, the complexity of the equipment and the time for reporting results are inconvenient to apply in a plurality of scenes of clinical detection, and the requirements on operation and maintenance are high. The method is inconvenient to apply in detection scenes of preoperative detection, primary hospitals and subdivision departments. The current trend of the miniaturization and convenient subdivision technology research and development becomes a technical hot spot more and more.
The immunochromatography is a well-developed technical scheme, and Chinese patent No. 201380015412.6 discloses an immunochromatography method in which a thiol polyalkylene glycol and/or its derivative is protected, and an arginine and casein apparatus are held in a dry holding part together with a label, thereby reducing interference caused by non-specific binding. Us patent 8043866 discloses a method for detecting signals by using silver ions reduced into silver nanoparticles; U.S. patent 8999730 discloses an immunochromatographic method that can detect low and high concentrations; U.S. Pat. No. 7993935 discloses an immunochromatographic test strip, but in the immunochromatographic method, the temperature, humidity, coating amount, quality of chromatographic membrane, high background due to nonspecific binding, and the like, make the immunochromatographic method unable to obtain an accurate quantitative test.
The microfluidic control technology is another technical hotspot, and US20150087079a1 discloses a microfluidic chip which can control the flow of liquid in a microfluidic channel by air pressure, a detection area of the chip is arranged in the channel, and the flowing liquid can contact with the channel. Us patent 20150087079a1 discloses a microfluidic liquid-controlled valve that can be shaped by external pressure to open and close a microchannel; us 20120282625a1 discloses a microfluidic chip with raised bottom channels; U.S. patent 8834813B2 discloses a dual flow channel, chip with flow channels directly communicating with each other; chinese patent 200910007020.0 discloses a microfluid processing centrifugal chip capable of performing liquid distribution, and us patent 9151750B2 discloses a centrifugal chip for performing liquid mixing flow operation using centrifugal force and geometric surface tension. The micro-fluidic technology avoids complex operations such as mechanical operation, liquid adding and mixing of a liquid path and the like, and is concerned, but the processing of a micro-channel, the sample coating, micro-sample transfer and mixing of the micro-channel make the precise reaction operation difficult to realize, the liquid equipment quantification of the micro-channel chip and the batch difference of the micro-channel can cause great precision loss, and the cost of the micro-fluidic chip is difficult to reduce due to the complexity of the micro-channel processing.
SUMMERY OF THE UTILITY MODEL
The utility model aims at providing an integrated biological sample detects chip can guarantee the convenience and the accuracy of liquid transfer control at the reaction time of accurate control liquid on the chip under the external magnetic field to greatly improved the control that the chip is used for biological detection reaction condition.
The utility model relates to an integrated biological sample detects chip contains:
at least one sample addition hole for adding a sample to be analyzed;
at least one reaction cell;
at least two reagent reservoirs;
the sample adding hole is connected with the reaction tank through a flow path, and the reagent liquid storage tank is connected with the reaction tank through a flow path;
the flow path is provided with at least one controllable valve for controlling the flow switch of the reagent in the reagent storage tank to the reaction tank;
the flow path is provided with at least one controllable valve for controlling the liquid discharge switch of the reagent reaction tank;
at least one magnetic material or a magnetic control material with interaction force with the magnetic material is arranged in the valve cavity as a moving element, and the flow path is opened and closed under the action of the magnetic force.
Preferably, the device further comprises a waste liquid pool, the waste liquid pool is connected with the reaction pool through a flow path, at least one controllable valve is arranged on the flow path, at least one magnetic material or a magnetic control material with interaction force with the magnetic material is arranged in a valve cavity as a moving element, and the flow path is opened and closed under the action of the magnetic force.
Furthermore, a sample diluting pool is arranged between the sample adding hole and the reaction pool, and a mixing component for mixing the sample is arranged in the sample diluting pool.
Furthermore, the sample diluting pool and the reaction pool respectively comprise a pre-diluting pool air hole and a reaction pool air hole which are connected with the outside, the pre-diluting pool air hole and the reaction pool air hole are sealed when the chip is packaged, and the pre-diluting pool air hole and the reaction pool air hole are opened before detection and are used for communicating and balancing atmospheric pressure.
Preferably, the reaction chamber contains a capture molecule for capturing a molecule to be analyzed in a sample.
Furthermore, the capture molecules are coated on a solid phase matrix or coated on the surface of the magnetic microspheres.
Furthermore, when the capture molecules are coated on the surfaces of the magnetic microspheres, the reaction tank is provided with a uniform mixing component.
The utility model has the advantages that: complicated mechanical, flow path and time sequence operations are integrated on the chip, the complexity of the operation and a plurality of reliability problems are avoided, and reagents on the chip are pre-quantitatively pre-assembled in advance, so that the quantitative accuracy of the liquid is ensured. Meanwhile, the liquid flowing and uniformly mixing operations of the chip are accurately controlled on the chip, the chip is designed by adopting valve control, the reaction time of the liquid on the chip can be accurately controlled under an external magnetic field, and the convenience and the accuracy of liquid mobilization control are ensured, so that the control of the chip on the biological detection reaction conditions is greatly improved. The flow path of the chip is designed by adopting valve control, the requirement on the flow path is reduced because the flow of microfluid is not relied on for quantification, the flow path with millimeter size can be adopted, the liquid quantification is not influenced by the flow path, the processing requirement on the flow path of the chip is reduced, and the cost and the process complexity of the chip are greatly reduced.
Drawings
Fig. 1 is a schematic structural diagram of an integrated biological sample detection chip.
FIG. 2 is a schematic diagram of a chip without a sample dilution cell.
FIG. 3 is an exemplary schematic diagram of a valve design of an integrated biological sample detection chip.
Fig. 4 is an embodiment of the control valve assembly.
FIG. 5 is a diagram illustrating the overall results of the integrated biological sample detection chip.
FIG. 6 is a schematic diagram of a valve structure of a design chip.
Detailed Description
In order to make the technical problem, technical solution and advantageous effects solved by the present invention more clearly understood, the following description of the present invention with reference to the accompanying drawings and embodiments is made.
As shown in fig. 1-5, the utility model relates to an integrated biological sample detects chip integration has application of sample hole 1, the sample can add the chip through application of sample hole 1, application of sample hole 1 can directly link to each other with reaction tank 16, can further have a sample dilution pool 2 between application of sample hole 1 and the reaction tank 16 and be used for diluting the sample, perhaps to the pretreatment of sample, can add mixing subassembly 3 in the sample dilution pool 2 and carry out the mixing to the dilution of sample, concrete scheme can be for adding possess with magnetism interact's steel ball be used for shaking under the plus magnetic field again and carry out the mixing.
The chip is integrated with reagent reservoirs 9, 10, the reagent reservoirs 9, 10 can be pre-filled with reagents, the reagents can be added into the reagent reservoirs 9, 10 through the reagent adding holes 6, 7, the reagent amount stored in the reagent reservoirs 9, 10 is not less than 10u L, so as to ensure the accuracy of the added reagent amount, the reagent reservoirs 9, 10 are connected with the reaction tank 16 through a second flow path 20 and a third flow path 12, a gas flow path is arranged at the other end of the reagent reservoirs 9, 10, when the reagents in the reagent reservoirs 9, 10 are released to the reaction tank 16, the gas flow path is in an open state and is connected with the atmospheric pressure for balancing the atmospheric pressure, control valves 14, 11 are arranged on the gas flow path through which the reagent reservoirs 9, 10 are communicated with the outside or on the second flow path 20 and the third flow path 12 through which the reagent reservoirs 9, 10 are connected with the reaction tank 16, and are preferably arranged on the second flow path 20 and the third flow path 12, and the second flow path 20 and the third flow path 12 are directly cut off.
A reaction pool 16 is integrated on the chip, the reaction pool 16 provides a reaction place, a sample is added into the reaction pool 16 through a sample adding hole 1 or a pretreated sample diluting pool 2, a valve 17 is arranged in a liquid path 18 connecting the reaction pool 16 with a waste liquid pool 19, the valve 17 is in a closed state when the sample is added, the staying time of the sample in the reaction pool 16 can be controlled through the opening time interval of the valve 17, the valve 17 can be opened to remove sample liquid when the sample reaches a preset time in the reaction pool 16, the valve 14 of a reagent liquid storage pool 9 is opened to add liquid into the reaction pool 16, the valve 17 is opened to release the reaction liquid in the reaction pool 16 after the liquid in the reagent liquid storage pool 9 stays in the reaction pool 16 for a specified time, meanwhile, the reagent liquid storage pool 10 can be synchronously opened or opened later, a reagent enters the reaction pool 16 to start the next reaction or the reaction pool 16 is cleaned, and fills the reaction cell to ensure that the medium providing the optical path or electrical signal is present during the detection.
The chip has at least two reagent reservoirs, which can further comprise more reagent reservoirs connected with the reaction tank 16, and valves are arranged on the connecting liquid paths.
The valve of the chip is provided with a magnetic material or a magnetic control material which can generate attraction or repulsion with the magnetic material, the material can move under an external force field so as to start the function of closing and opening the flow path, and the specific valve can be designed in a changeable way.
As shown in FIG. 3, a valve is exemplified, wherein ①, ② show that two materials are adopted, a long strip-shaped cavity is used for liquid path control, black materials are mutually attracted, ① shows a flow path closed state, ② shows a flow path open state, ③, ④ show oval cavities for flow path control, black materials are mutually attracted, ③ shows a flow path closed state, ④ shows a flow path open state, ② 0, ② 1 shows that the two mutually attracted materials of the control valve are in parallel positions, the materials in the states have relatively large attraction force, ⑤ shows a closed body of the valve, ⑥ shows an open state of the valve, ② 2, ② 3, ② 4, ② 5 show that the materials shown in black are blocked by surface tension of natural fluid and fluid action, the flow path is converted into an open state under the action of external magnetic force, the valve is designed to enable an external magnetic field to control the opening and closing of the chip without invading into the chip, the specific design of the valve can enable a plurality of materials to be in a sealed state, a variety of solid materials, a ferrite material can be easily stored in a sealed state, a sealed liquid flow path without using a solid metal material, and a solid material, such as a solid material, a liquid flow path, a solid material, a solid.
The liquid flow of the chip is preferably controlled by using gravity and hydrophilic and hydrophobic force between the liquid and the flow path, and air pressure, and preferably, the gravity and hydrophilic and hydrophobic force between the liquid and the flow path are used as driving force for the liquid flow in the chip, and when the chip is used, the sample application hole 1 of the chip is vertically higher than the reaction tank 16, the reagent reservoirs (9, 10) of the chip are vertically higher than the reaction tank 16, and the waste liquid reservoir 19 of the chip is vertically lower than the reaction tank 16 of the chip by using the gravity as the driving force.
The reaction cell 16 of the chip is a place for reaction, and the sample solution and the reagents of the reagent reservoirs 9 and 10 can flow into the reaction cell 16 to perform reaction and washing operations. The sample dilution pool 2 can be coated with capture molecules or assembled with a chip coated with capture molecules for capturing biomolecules in the sample, and the biomolecules can further react with a labeling reagent contained in the reagent reservoir 9 to perform labeling, such as fluorescent micro-or quantum dot ball labeled antibodies, and then are washed with a reagent contained in the reagent reservoir 10 and filled in the reaction pool, excited by laser irradiation, and fluorescence detection is performed by using a PMT (photomultiplier tube) or a CCD (image sensor). The sample diluting pool 2 can also be pre-loaded with magnetic microspheres which are marked with capture antibodies, the reaction pool 16 is externally applied with a magnetic field, so that the microspheres are kept in the reaction pool 16, meanwhile, the sample can be added into the reaction pool 16 to be combined with the magnetic microsphere marked capture molecules, and the reagent in the reagent liquid storage pool can enter the reaction pool 16 through the control of a valve. The reagent in the reagent liquid storage pool can be a fluorescence labeling reagent, a quantum dot labeling reagent, an enzyme labeling antibody, acridinium ester and other labeling reagents, and if the reagent is an enzyme labeling reagent or an acridinium labeling reagent, a substrate reaction reagent is further added in the liquid storage pool.
The reaction tank 16 can be pre-filled with small balls with millimeter-sized diameters, the reagent liquid storage tank can be filled with latex reagents, a sample is added into the sample dilution tank 2 and further enters the reaction tank 16, the small balls move through a uniform mixing system under the action of a magnetic field, the latex reagents are further added, and the reaction time is controlled to carry out sample detection.
In order to control the operation reaction of the reagent, biological samples can be detected by applying various principles on the basis of a chip, and the chip can also be integrated with electrodes to detect the samples by an electrochemical method.
The detection method of the integrated biological sample comprises the following specific steps:
a. placing the chip in an instrument with magnetic disconnection and on-multipoint control, wherein the magnetic control points correspond to the positions of magnetic materials 21, 22, 23 and 24 of the chip, and the magnetic control points do not invade a first flow path 15, a second flow path 20, a third flow path 12 and a fourth flow path 18 of the chip;
b. the sample is added into the sample adding hole 1, and the sample directly flows into the reaction tank 16 or flows into the reaction tank 16 after being pretreated by the sample diluting tank 2;
c. after the reaction is carried out for a fixed time, the valve 17 of the reaction tank 16 is opened through the magnetic control of a control instrument, and the reaction liquid in the reaction tank 16 is discharged;
d. the valves 14 and/or 11 of the reagent reservoir 9 and/or the reagent reservoir 10 are opened through the magnetic control of the control instrument, and the liquid of the reagent reservoir 9 and/or the reagent reservoir 10 flows into the reaction tank 16;
e. after the reaction is carried out for a fixed time, the valve 17 of the reaction tank 16 is opened through the magnetic control of a control instrument;
f. controlling the temperature of the system in the chip to be constant through a temperature control module;
g. the biological reaction in the reaction cell 16 is detected by using a photomultiplier, an image sensor, a photoelectric tube, and an electrode.
Further, when the reaction chamber 16 contains capture molecules coated on magnetic microspheres, the control device further comprises magnetic control points corresponding to the positions of the reaction chamber 16, and the magnetic control points are used for adsorbing and retaining the magnetic microspheres when the reaction chamber reagents are washed and discharged.
During the detection process, the reaction chamber 16 can be filled with the liquid of the reagent reservoir 10 to reduce interference and serve as a medium for an optical path or an electric path. The whole reaction controls the reaction temperature in the machine in the instrument. The machine may install a pre-heated bin for pre-heating spare chips.
The specific fixed reaction time in the reaction process is different according to the difference of specific reaction systems, optimization and combination can be carried out on the valve control of the chip, the temperature in the reaction process is set according to the specific reaction, the temperature in the biological sample is generally 37 ℃, the temperature is close to the temperature in the human body of the biological sample, and the specific reaction can increase the temperature so as to accelerate the reaction speed and improve the reaction signal.
During the reaction, the reagent reservoir 10 may serve to clean the reaction chamber and may also have a reactivity for detection, such as a luminescent substrate solution. The sample diluting pool 2 and the reaction pool 16 respectively comprise a pre-diluting pool air hole 4 and a reaction pool air hole 5 which are connected with the outside, the chip can further comprise an air control component connected with the pre-diluting pool air hole 4 and the reaction pool air hole 5, and the chip is arranged in the instrument to drive the liquid to flow through air pressure.
As shown in fig. 4, the magnetically attracted magnetic materials 21, 22, 23, 24 are assembled in the chip, the substrate shown in fig. 5 is covered with a cover plate 29, the thickness of the cover plate 29 is 1mm, the cover plate 29 and the chip form a detection area 31, the magnetic material is PP (polypropylene) material, and the magnets 25, 26, 27, 28 are assembled on the surface of the cover plate 29 of the chip. Fig. 6 shows a valve structure of a chip, where a is a valve body before magnetic material is implanted, B is a valve body in a closed state, and C is a valve body in an open state.
The basic assembly of the chip is with magnetic material, further encapsulating the closing plate, fig. 5 is an overall schematic diagram of the integrated chip, the integrated chip forms a closed system, and the magnetic material 25, 26, 27, 28 mounted on the cover plate and 21, 22, 23, 24 on the bottom plate attract to move the implanted material inside to the position of the closed liquid path.
As shown in fig. 2, in embodiment 1, the sample dilution cell 2 is not included, and after the closed plate is assembled to the chip, the magnets 25, 26, 27, and 28 in embodiment 1 are replaced with the magnetically attractive alloy magnet embedded in the chip and then assembled to the chip.
The above description is only the preferred embodiment of the present invention, and is not intended to limit the present invention, and any modifications, equivalent replacements, and improvements made within the spirit and principles of the present invention should fall within the protection scope of the present invention.
Claims (7)
1. An integrated biological sample detection chip, comprising:
at least one well (1) for the introduction of a sample to be analysed;
at least one reaction cell (16);
at least two reagent reservoirs (9, 10);
the sample addition hole (1) is connected with the reaction tank (16) through a first flow path (15), and the reagent reservoirs (9, 10) are connected with the reaction tank (16) through a second flow path (20) and a third flow path (12);
at least one controllable valve (14, 11) is arranged on the second flow path (20) and the third flow path (12) for controlling the flow switch of the reagent in the reagent storage tanks (9, 10) to the reaction tank (16);
at least one controllable valve (13) is arranged on the first flow path (15) and used for controlling the liquid discharge switch of the reagent reaction tank (16);
the valve (13, 14, 11) has at least one magnetic material (22, 23, 24) or a magnetic control material (28, 25, 26) as a moving element in a chamber, and opens and closes the first flow path (15), the second flow path (20) and the third flow path (12) by a magnetic force.
2. The integrated biological sample detection chip of claim 1, wherein: the device also comprises a waste liquid pool (19), wherein the waste liquid pool (19) is connected with the reaction pool (16) through a fourth flow path (18), at least one controllable valve (17) is arranged on the fourth flow path (18), at least one magnetic material (21) or a magnetic control material (27) which has interaction force with the magnetic material is arranged in the cavity of the valve (17) and is used as a moving element, and the fourth flow path (18) is opened and closed under the action of the magnetic force.
3. The integrated biological sample detection chip of claim 2, wherein: a sample diluting pool (2) is arranged between the sample adding hole (1) and the reaction pool (16), and a uniform mixing component (3) for uniformly mixing the sample is arranged in the sample diluting pool (2).
4. The integrated biological sample detection chip of claim 3, wherein: the sample diluting pool (2) and the reaction pool (16) respectively comprise a pre-diluting pool air hole (4) and a reaction pool air hole (5) which are connected with the outside, the pre-diluting pool air hole (4) and the reaction pool air hole (5) are sealed when a chip is packaged, and the pre-diluting pool air hole and the reaction pool air hole are opened before detection and are used for communicating and balancing atmospheric pressure.
5. The integrated biological sample detection chip of claim 1, wherein: the reaction chamber (16) contains a capture molecule for capturing a molecule to be analyzed in a sample.
6. The integrated biological sample detection chip of claim 5, wherein: the capture molecules are coated on a solid phase matrix or coated on the surface of the magnetic microspheres.
7. The integrated biological sample detection chip of claim 6, wherein: when the capture molecules are coated on the surfaces of the magnetic microspheres, the reaction tank (16) is provided with a uniform mixing component (3).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201921245270.3U CN210965157U (en) | 2019-08-02 | 2019-08-02 | Integrated biological sample detection chip |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201921245270.3U CN210965157U (en) | 2019-08-02 | 2019-08-02 | Integrated biological sample detection chip |
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| CN210965157U true CN210965157U (en) | 2020-07-10 |
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| CN201921245270.3U Expired - Fee Related CN210965157U (en) | 2019-08-02 | 2019-08-02 | Integrated biological sample detection chip |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110354924A (en) * | 2019-08-02 | 2019-10-22 | 郭长春 | A kind of integrated bio pattern detection chip and detection method |
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2019
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110354924A (en) * | 2019-08-02 | 2019-10-22 | 郭长春 | A kind of integrated bio pattern detection chip and detection method |
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