Chromatographic detection device and chromatographic detection method

Abstract

The invention belongs to the technical field of biological sample detection, and discloses a chromatographic detection device and a chromatographic detection method. The chromatography detection device comprises magnetic sensitive particles, a measurement carrier, a magnetic field magnetization mechanism, a magnetic field measurement mechanism and a moving mechanism. A conjugate is attached to the magnetic sensitive particles; the measurement carrier is sequentially provided with a sample pad and a test position along the chromatography direction; and the magnetic field measuring mechanism is used for measuring the magnetic field intensity of the magnetized magnetic sensitive particles at the test position so as to obtain the content of the target object in the to-be-measured body. The magnetic field directions of the magnetic-sensitive particles are consistent through the magnetic field magnetization mechanism, so that the measurement of the measuring device is more accurate. The magnetic field component, detected by the magnetic field measuring mechanism, of the magnetic-sensitive particles at the test position is periodically changed through the moving mechanism, so that the magnetic field, detected by the magnetic field measuring mechanism, of the magnetic-sensitive particles at the test position is a dynamic magnetic field, other static magnetic field interference can be eliminated when magnetic field signals are measured, and the sensitivity and accuracy of the detection device are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of biological sample detection, and in particular to a chromatographic detection device and a chromatographic detection method. Background Art

[0002] Lateral flow immunodiagnosis is a simple, rapid, low-cost immunological qualitative or quantitative detection technology based on the combination of immunotechnology and chromatographic technology. It is a widely used medical bedside detection solution. Its technical principle is based on the immune binding reaction between the target analyte and its ligand / receptor (such as the antigen-antibody to be tested), so that the targeted immune probe is specifically aggregated on the detection strip and read, thereby obtaining the qualitative or quantitative results corresponding to the target analyte.

[0003] Conventional immune probes mainly include latex microspheres, colloidal gold, quantum dots, upconversion particles and other new nanoparticles, and the signal reading method is mostly optical recognition. Due to the non-specific binding and background fluorescence interference caused by the complex cost of the sample to be tested, the detection sensitivity is low, the accuracy and consistency are poor, and it cannot meet the high sensitivity and high precision detection requirements of low-abundance biomarkers in certain diseases (such as neurological, autoimmune, tumor, heart, etc.).

[0004] The prior art uses magnetizable particles to detect magnetic field signals to reduce the interference of nonspecific binding and background fluorescence. However, the direction of the magnetic field of the magnetizable particles is disordered, and the measuring device cannot accurately measure the magnetic field strength. In addition, when the detection device measures the magnetic field signal, the magnetic field signal of the magnetizable particles is very weak and is easily interfered by, for example, the earth's magnetic field or other magnetic fields generated by other electronic devices, which makes the sensitivity and accuracy of the detection device low. Summary of the invention

[0005] The object of the present invention is to provide a chromatographic detection device and a chromatographic detection method, which can accurately measure the magnetic field strength with high sensitivity and high precision, and meet the needs for the detection of low-abundance biomarkers.

[0006] To achieve this object, the present invention adopts the following technical solutions:

[0007] In one aspect, a chromatography detection device is provided, comprising:

[0008] Magnetic sensitive particles, on which a binding substance for specific binding with a target is attached;

[0009] The measuring carrier is provided with a sample pad and a test position in sequence along the chromatography direction, the sample pad is used to hold the magnetic sensitive particles and the object to be tested containing the target, and the test position is used to capture the target;

[0010] A magnetic field magnetization mechanism for magnetizing the magnetic-sensitive particles at the test position to make the magnetic field directions of the magnetic-sensitive particles at the test position consistent;

[0011] A magnetic field measurement mechanism for measuring the magnetic field intensity after magnetization of the magnetic-sensitive particles at the test position to obtain the content of the target substance in the object to be measured;

[0012] A moving mechanism, on which the measurement carrier is arranged, and the moving mechanism is used to periodically change the magnetic field component of the magnetic-sensitive particles at the test position detected by the magnetic field measurement mechanism.

[0013] Preferably, the moving mechanism is used to periodically change the distance or the magnetic field direction of the magnetic-sensitive particles at the test position relative to the magnetic field measurement mechanism.

[0014] Preferably, the measurement carrier is a lateral flow test strip, on which a test line and a quality control line are provided. The test line serves as the test position, and the quality control line is used to verify the effectiveness of the chromatography result.

[0015] Preferably, when the moving mechanism operates, the magnetic field component of the magnetic-sensitive particles at the quality control line detected by the magnetic field measurement mechanism remains unchanged.

[0016] Preferably, the moving mechanism is a rotating mechanism, and the rotation axis of the rotating mechanism is offset from the measurement center of the magnetic field measurement mechanism; the rotation axis of the rotating mechanism coincides with the quality control line; the magnetic field magnetization mechanism is further used to magnetize the magnetic-sensitive particles at the quality control line to make the magnetic field directions of the magnetic-sensitive particles at the quality control line consistent, and to make the magnetic field direction of the magnetic-sensitive particles at the quality control line collinear with the rotation axis of the rotating mechanism.

[0017] Preferably, the chromatography detection device further includes a magnetic flux concentrator for concentrating the magnetic field lines of the magnetic field of the magnetized magnetic-sensitive particles to the magnetic field measurement mechanism.

[0018] Preferably, the chromatography detection device further includes a magnetic shielding mechanism for shielding external interfering magnetic fields; the magnetic shielding mechanism is provided with an inner cavity, and the measurement carrier, the magnetic field magnetization mechanism and the magnetic field measurement mechanism are all located in the inner cavity.

[0019] On the other hand, a chromatography detection method is provided, which uses the chromatography detection device described in any of the above solutions for detection, and the chromatography detection method includes:

[0020] Fully mixing the magnetic-sensitive particles attached with the conjugate with the object to be measured, and the conjugate is used to specifically bind to the target substance;

[0021] Dropping the mixture of the magnetic sensitive particles and the object to be tested on the sample pad of the measuring carrier, the magnetic sensitive particles move toward the test position, and the test position is used to specifically bind to the target object;

[0022] Magnetizing the magnetically sensitive particles on the measuring carrier so that the directions of the magnetic fields of the magnetically sensitive particles are consistent;

[0023] The measuring carrier is moved to drive the test position to move, so as to periodically change the magnetic field component of the magnetic sensitive particles at the test position detected by the magnetic field measuring mechanism;

[0024] The magnetic field strength at the test position is measured by the magnetic field measuring mechanism to detect the target object.

[0025] Preferably, moving the measurement carrier to drive the test position to move so as to periodically change the magnetic field component detected by the magnetic field measuring mechanism of the magnetic sensitive particles at the test position includes:

[0026] The measuring carrier is rotated to drive the test position to rotate, and the rotation axis is staggered with the measuring center of the magnetic field measuring mechanism; or,

[0027] The measuring carrier is made to move linearly back and forth to drive the test position to move linearly back and forth, and the path of the test position is staggered with the measurement center of the magnetic field measuring mechanism during the linear reciprocating translation; or,

[0028] The measuring carrier is made to move back and forth to drive the test position to move back and forth linearly, and the path of the test position is made to be collinear with the measurement center axis of the magnetic field measuring mechanism during the linear reciprocating translation, and the magnetic field direction of the magnetically sensitive particles at the test position is not perpendicular to the path of the test position.

[0029] Preferably, the magnetic field component variation period of the magnetic sensitive particles at the test position detected by the magnetic field measuring mechanism is T;

[0030] The tomographic detection method further includes demodulating and analyzing the magnetic field signal detected by the magnetic field measurement mechanism to obtain a signal with a period of T for detecting the target object.

[0031] Preferably, the tomography detection method further comprises retaining only the test position on the measurement carrier after completing the lateral tomography, and then detecting the magnetic field at the test position.

[0032] Preferably, the measurement carrier is sequentially provided with the sample pad, the test line, and the quality control line along the chromatography direction. The mixture of the magnetic sensitive particles and the analyte to be measured is dropped onto the sample pad of the measurement carrier, and the test line is used for specifically binding to the target substance;

[0033] After lateral chromatography is completed, magnetize the magnetic sensitive particles on the measurement carrier so that the magnetic field directions of the magnetic sensitive particles at the test line are consistent, and the magnetic field direction of the magnetic sensitive particles at the quality control line is collinear with the quality control line;

[0034] Rotate the measurement carrier with the quality control line as the rotation axis to periodically change the magnetic field component of the magnetic sensitive particles at the test position detected by the magnetic field measurement mechanism;

[0035] Measure the magnetic field intensity of the test line through the magnetic field measurement mechanism;

[0036] Demodulate and analyze the magnetic field signal detected by the magnetic field measurement mechanism to obtain a signal with a rotation period of T for detecting the target substance.

[0037] Preferably, the measurement center of the magnetic field measurement mechanism is offset from the quality control line.

[0038] Advantages of the present invention:

[0039] The chromatography detection device provided by the present invention includes magnetic sensitive particles, a measurement carrier, a magnetic field magnetization mechanism, a magnetic field measurement mechanism, and a moving mechanism. A binding substance for specifically binding to a target substance is attached to the magnetic sensitive particles. The measurement carrier is sequentially provided with a sample pad and a test position along the chromatography direction. The sample pad is used to hold the magnetic sensitive particles and the analyte containing the target substance, and the test position is used to capture the target substance; the magnetic field measurement mechanism is used to measure the magnetic field intensity of the magnetized magnetic sensitive particles at the test position to obtain the content of the target substance in the analyte. The magnetic field magnetization mechanism is used to magnetize the magnetic sensitive particles at the test position so that the magnetic field directions of the magnetic sensitive particles are consistent, enabling the magnetic field measurement mechanism to more accurately measure the magnetic field intensity. The measurement carrier is arranged on the moving mechanism, and the magnetic field component of the magnetic sensitive particles at the test position detected by the magnetic field measurement mechanism is periodically changed through the moving mechanism, so that the magnetic field detected by the magnetic field measurement mechanism for the magnetic sensitive particles at the test position is a dynamic magnetic field, and interference from other static magnetic fields can be excluded when measuring the magnetic field signal, improving the sensitivity and accuracy of the detection device. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 is a schematic structural diagram of the chromatography detection device provided by the present invention;

[0041] Figure 2 is a schematic structural diagram of the lateral chromatography test strip before chromatography involved in the present invention;

[0042] Figure 3 is a schematic structural diagram of the lateral flow test strip after chromatography (with the target substance) involved in the present invention;

[0043] Figure 4 is a schematic structural diagram of the lateral flow test strip after chromatography (without the target substance) involved in the present invention;

[0044] Figure 5 is a schematic structural diagram of the moving mechanism being a rotating mechanism involved in the present invention;

[0045] Figure 6 is a schematic structural diagram of the moving mechanism being a translation mechanism involved in the present invention;

[0046] Figure 7 is a schematic structural diagram of the moving mechanism being a lifting mechanism involved in the present invention;

[0047] Figure 8 is a schematic structural diagram of the transmission mechanism, measurement carrier and moving mechanism involved in the present invention.

[0048] In the figure:

[0049] 1, magnetic sensitive particles; 2, measurement carrier; 21, test line; 22, quality control line; 3, magnetic field magnetization mechanism; 4, magnetic field measurement mechanism; 5, moving mechanism; 51, driving part; 6, magnetic flux concentrator; 7, magnetic shielding mechanism; 8, transmission mechanism. Specific embodiments

[0050] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It can be understood that the specific embodiments described herein are only used to explain the present invention, rather than limiting the present invention. Additionally, it should be noted that for the sake of description, only the parts related to the present invention rather than all the structures are shown in the drawings.

[0051] In the description of the present invention, unless otherwise clearly defined and limited, the terms "connected", "connected to", "fixed" shall be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or integrated; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the internal communication of two components or the interaction relationship between two components. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0052] In the present invention, unless otherwise clearly specified and defined, the first feature being "on" or "under" the second feature may include the direct contact between the first and second features, or may include the situation where the first and second features are not in direct contact but in contact through additional features therebetween. Moreover, the first feature being "above", "over" and "on top of" the second feature includes that the first feature is directly above and obliquely above the second feature, or merely indicates that the horizontal height of the first feature is higher than that of the second feature. The first feature being "under", "beneath" and "underneath" the second feature includes that the first feature is directly below and obliquely below the second feature, or merely indicates that the horizontal height of the first feature is lower than that of the second feature.

[0053] In the description of this embodiment, the orientation or positional relationships such as "up", "down", "right", etc. are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of description and simplifying the operation, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as a limitation to the present invention. In addition, the terms "first" and "second" are only used for distinction in description and have no special meaning.

[0054] As Figures 1 to 8 shown, the present invention provides a chromatographic detection device, which includes magnetic sensitive particles 1, a measurement carrier 2, a magnetic field magnetization mechanism 3, a magnetic field measurement mechanism 4 and a moving mechanism 5. A binding substance is attached to the magnetic sensitive particles 1, and the binding substance is an antibody or antigen of the target substance, which is used for specifically binding with the target substance, so that the target substance is attached to the magnetic sensitive particles 1. The measurement carrier 2 is sequentially provided with a sample pad and a test position along the chromatographic direction. The sample pad is used for receiving the magnetic sensitive particles 1 and the test sample containing the target substance, and a binding substance is provided at the test position for capturing the target substance. During lateral chromatography, the magnetic sensitive particles 1 move towards the test position. A binding substance specifically binding with the target substance is provided at the test position, and the target substance is captured at the test position, so that the magnetic sensitive particles 1 attached with the target substance stay at the test position.

[0055] The magnetic field measurement mechanism 4 is used for measuring the magnetic field strength of the magnetized magnetic sensitive particles 1 at the test position to obtain the content of the target substance in the test sample. The magnetic field magnetization mechanism 3 is used for magnetizing the magnetic sensitive particles 1 at the test position to make the magnetic field directions of the magnetic sensitive particles 1 at the test position consistent. By the magnetic field magnetization mechanism 3, the magnetic field direction of the magnetic sensitive particles 1 is made, so that the magnetic field measurement mechanism 4 can more accurately measure the magnetic field strength of the magnetic sensitive particles 1 at the test position.

[0056] The measurement carrier 2 is disposed on the moving mechanism 5, and the moving mechanism 5 is used to periodically change the magnetic field component detected by the magnetic field measuring mechanism 4 of the magnetic sensitive particles 1 at the test position. Since the magnetic field signal of the magnetic sensitive particles 1 is very weak, when the magnetic field measuring mechanism 4 measures the magnetic field signal of the magnetic sensitive particles 1 at the test position, it is easily interfered by the magnetic field signals generated by the earth or other electronic devices. However, most of the interfering magnetic fields are static magnetic fields. By periodically changing the magnetic field component detected by the magnetic field measuring mechanism 4 of the magnetic sensitive particles 1 at the test position, the magnetic field detected by the magnetic field measuring mechanism 4 of the magnetic sensitive particles 1 at the test position becomes a dynamic magnetic field. Furthermore, the magnetic field measuring mechanism 4 can exclude the interference of other static magnetic fields during measurement. Therefore, the sensitivity and accuracy of the detection device are improved. In addition, the change in the distance between the magnetic sensitive particles 1 and the magnetic field measuring mechanism 4 can also be non-periodic, as long as it can be detected by the magnetic field measuring mechanism 4.

[0057] Optionally, the magnetic sensitive particles 1 can be iron (Fe), nickel (Ni), cobalt (Co), iron oxide (Fe3O4), and rare earth magnets. Among them, the rare earth magnets can be neodymium (Nd), terbium (Tb), or gadolinium (Gd). Further, the diameter of the magnetic sensitive particles 1 is 10 nanometers - 10 micrometers. The magnetic sensitive particles 1 include a core magnetic sensitive structure, a polymer material layer wrapped outside the core magnetic sensitive structure, and a functional ligand wrapped outside the polymer material layer. Among them, the polymer material can be polystyrene or polyvinyl chloride, and the functional ligand can be -NH2, -COOH, -OH, or -CHO.

[0058] Optionally, in this embodiment, the measurement carrier 2 is a lateral flow test strip, which is simple to operate and low in cost. As Figure 2 shown, a test line 21 and a quality control line 22 are provided on the lateral flow test strip. The test line 21 serves as the test position, and the quality control line 22 is used to verify the effectiveness of the chromatography result. Under the action of lateral flow chromatography, the mixture of the analyte containing the target and the magnetic sensitive particles 1 moves in the direction of the test line 21. A binding substance specifically binding to the target is provided at the test line 21, and the target is captured at the test line 21. Furthermore, the magnetic sensitive particles 1 attached with the target stay at the test line 21, and the magnetic sensitive particles 1 not attached with the target move to the quality control line 22. After that, by measuring the magnetic field intensity of the magnetic sensitive particles 1 at the test line 21, the content of the target in the analyte can be accurately measured. After the lateral flow chromatography is completed, as Figure 3 and Figure 4 shown, if there are magnetic sensitive particles 1 staying at the test line 21, the analyte contains the target. If there are no magnetic sensitive particles 1 staying at the test line 21, the analyte does not contain the target.

[0059] Optionally, the lateral flow test strip further includes a nitrocellulose membrane, i.e., an NC membrane. The NC membrane serves as a chromatography carrier and chromatographs the mixture through capillary action. In addition, the lateral flow test strip further includes absorbent paper, which can provide a certain suction force to draw the mixture across the NC membrane and collect the liquid after chromatography, thereby improving the test sensitivity.

[0060] Optionally, in this embodiment, the magnetic field magnetization mechanism 3 includes a signal generator, a set of symmetric electromagnets, and a coil circuit board. Driven by the signal generator, a modulated magnetic field is generated to magnetize the magnetic sensitive particles 1 at the test line 21.

[0061] Optionally, the magnetic field measurement mechanism 4 can be a fluxgate, a Hall sensor, or a SQUID sensor. In this embodiment, the magnetic field measurement mechanism 4 is an atomic magnetometer. The magnetic measurement sensitivity of the atomic magnetometer can reach 10 fT / Hz. Compared with traditional fluxgates, Hall sensors, or SQUID sensors, the atomic magnetometer does not require a low-temperature environment for operation, is easy to operate, has high sensitivity, and the test results are stable and reliable. Further, the atomic magnetometer includes a magnetometer probe and a signal acquisition and processor. The magnetometer probe is used to detect the magnetic field, and the signal acquisition and processor is used to acquire and process the magnetic field signal.

[0062] Optionally, the moving mechanism 5 is used to periodically change the distance or the magnetic field direction of the magnetic sensitive particles 1 at the test position relative to the magnetic field measurement mechanism 4. By periodically changing the distance of the magnetic sensitive particles 1 relative to the magnetic field measurement mechanism 4, the magnitude of the magnetic field detected by the magnetic field measurement mechanism 4 for the magnetic sensitive particles 1 is changed. By periodically changing the magnetic field direction of the magnetic sensitive particles 1 relative to the magnetic field measurement mechanism 4, the direction of the magnetic field detected by the magnetic field measurement mechanism 4 for the magnetic sensitive particles 1 is changed. When the moving mechanism 5 is working, the magnetic field component detected by the magnetic field measurement mechanism 4 for the magnetic sensitive particles 1 at the quality control line 22 remains unchanged, avoiding the interference of the magnetic sensitive particles 1 on the quality control line 22 and improving the sensitivity and accuracy of detecting the target substance.

[0063] Optionally, the moving mechanism 5 includes a driving member 51, which plays a driving role. Optionally, in this embodiment, as Figure 5As shown, the moving mechanism 5 is a rotating mechanism. By driving the measurement carrier 2 to rotate at a certain frequency, the distance or the magnetic field direction between the magnetic-sensitive particles 1 and the magnetic field measurement mechanism 4 will change periodically. That is to say, a part of the magnetic field signal measured by the magnetic field measurement mechanism 4 will change periodically. This part of the signal is the signal generated by the magnetic-sensitive particles 1, that is, the target signal. In addition, the rotating mechanism further includes a turntable, and the measurement carrier 2 is arranged on the turntable. The use of the turntable has a simple structure. The turntable is driven to rotate by the driving member 51 to change the distance or the magnetic field direction between the magnetic-sensitive particles 1 and the magnetic field measurement mechanism 4. Further, in this embodiment, the driving member 51 of the rotating mechanism is a motor. In other embodiments, the driving member 51 of the rotating mechanism may also be a hydraulic motor, a cylinder or other driving structures, which is not limited to this embodiment.

[0064] Further, in this embodiment, the rotation axis of the rotating mechanism is offset from the measurement center of the magnetic field measurement mechanism 4, that is, the measurement center is not on the rotation axis, which can ensure that both the distance and the magnetic field direction of the magnetic-sensitive particles 1 at the test line 21 relative to the magnetic field measurement mechanism 4 change. If the measurement center of the magnetic field measurement mechanism 4 is on the rotation axis of the rotating mechanism, during the rotation process, the distance between the magnetic-sensitive particles 1 at the test line 21 and the magnetic field measurement mechanism 4 remains unchanged. On this basis, if the test line 21 coincides with the rotation axis of the rotating mechanism and the magnetic field direction of the magnetic-sensitive particles 1 at the test line 21 is collinear with the rotation axis of the rotating mechanism, then both the distance and the magnetic field direction of the magnetic-sensitive particles 1 at the test line 21 relative to the magnetic field measurement mechanism 4 remain unchanged, and the magnetic field component detected by the magnetic field measurement mechanism 4 remains unchanged. Then, the magnetic field detected by the magnetic field measurement mechanism 4 for the magnetic-sensitive particles 1 at the test line 21 is a static magnetic field, and the interference of other magnetic fields cannot be excluded.

[0065] Furthermore, the rotation axis of the rotation mechanism coincides with the quality control line 22. The magnetic field magnetization mechanism 3 is further configured to magnetize the magnetic sensitive particles 1 at the quality control line 22 to make the magnetic field directions of the magnetic sensitive particles 1 at the quality control line 22 consistent, and make the magnetic field direction of the magnetic sensitive particles 1 at the quality control line 22 collinear with the rotation axis of the rotation mechanism. After lateral chromatography, the magnetic sensitive particles 1 that do not adhere to the target will move to the quality control line 22. When the magnetic field magnetization mechanism 3 magnetizes the magnetic sensitive particles 1 at the test line 21, the magnetic sensitive particles 1 on the quality control line 22 may also be magnetized. Furthermore, the magnetic field measurement mechanism 4 may also measure the magnetic field strength of the magnetic sensitive particles 1 at the quality control line 22. At the same time, since the quality control line 22 is on the measurement carrier 2, when the moving mechanism 5 periodically changes the distance or magnetic field direction of the magnetic sensitive particles 1 at the test position relative to the magnetic field measurement mechanism 4, the magnetic sensitive particles 1 at the quality control line 22 will also change periodically. Coinciding the rotation axis of the rotation mechanism with the quality control line 22 can first ensure that the distance of the magnetic sensitive particles 1 on the quality control line 22 relative to the magnetic field measurement mechanism 4 remains unchanged during rotation. Further, magnetizing the magnetic sensitive particles 1 at the quality control line 22 by the magnetic field magnetization mechanism 3 to make the magnetic field direction of the magnetic sensitive particles 1 at the quality control line 22 collinear with the rotation axis of the rotation mechanism can ensure that the magnetic field direction of the magnetic sensitive particles 1 at the quality control line 22 relative to the magnetic field measurement mechanism 4 remains unchanged during rotation. Thus, the magnetic field component detected by the magnetic field measurement mechanism 4 for the magnetic sensitive particles 1 at the quality control line 22 remains unchanged, thereby avoiding the interference of the magnetic sensitive particles 1 on the quality control line 22 and improving the sensitivity and accuracy of the measurement.

[0066] In some alternative embodiments, as Figure 6 shown, the moving mechanism 5 may be a translation mechanism. The translation mechanism drives the measurement carrier 2 to move horizontally back and forth or in other forms of movement to approach or move away from the magnetic field measurement mechanism 4, thereby changing the distance or magnetic field direction of the magnetic sensitive particles 1 at the test position relative to the magnetic field measurement mechanism 4. Further, the translation mechanism may be a conveyor belt, or a rack and pinion mechanism, a crank-slider mechanism, or other mechanisms, as long as it can achieve periodic or non-periodic translation of the measurement carrier 2. Further, the driving member 51 of the translation mechanism may be a motor, a cylinder, a hydraulic cylinder, or other driving structures.

[0067] In other alternative embodiments, as Figure 7 shown, the moving mechanism 5 may also be a lifting mechanism. The lifting mechanism drives the measurement carrier 2 to move up and down reciprocally to approach or move away from the magnetic field measurement mechanism 4, thereby changing the distance or magnetic field direction of the magnetic sensitive particles 1 at the test position relative to the magnetic field measurement mechanism 4. The lifting mechanism may be a motor-driven worm and gear mechanism, a hydraulic rod mechanism, a cylinder mechanism, or other mechanisms, as long as it can achieve periodic or non-periodic up and down movement of the measurement carrier 2. In addition, the moving mechanism 5 may also be other mechanisms, as long as it can change the distance of the measurement carrier 2 relative to the magnetic field measurement mechanism 4.

[0068] Optionally, a first clamp is provided on the moving mechanism 5 for clamping the measurement carrier 2. Further, the first clamp can be a jaw, a buckle, or other structures, as long as it can clamp and release the measurement carrier 2. Further, the first clamp can be loosened and tightened manually, with low cost; or it can be loosened and tightened electrically to achieve full-automatic detection.

[0069] Optionally, the chromatography detection device further includes a magnetic flux concentrator 6 for concentrating the magnetic field lines of the magnetized magnetic sensitive particles 1 to the magnetic field measurement mechanism 4, further improving the measurement accuracy of the magnetic field measurement mechanism 4 for the magnetic field of the magnetized magnetic sensitive particles 1.

[0070] Optionally, the chromatography detection device further includes a magnetic shielding mechanism 7. The magnetic shielding mechanism 7 is provided with an inner cavity, and the measurement carrier 2, the magnetic field magnetization mechanism 3, and the magnetic field measurement mechanism 4 are all located in the inner cavity. The magnetic shielding mechanism 7 is used to shield external interfering magnetic fields, such as the earth's magnetic field and the motor magnetic field, etc., to improve the measurement accuracy of the magnetic field measurement mechanism 4 for the magnetic field of the magnetized magnetic sensitive particles 1. In this embodiment, the magnetic shielding device includes a magnetic shielding cylinder composed of multiple layers of permalloy and a magnetic field compensation coil to shield the external magnetic field and provide a uniform area required for measurement. In other alternative embodiments, the magnetic shielding device includes a magnetic shielding cover or a magnetic shielding layer made of a high magnetic permeability material, where the high magnetic permeability material can be Teflon, permalloy, ferrite, iron, neodymium iron boron magnet, or other materials. In addition, the magnetic shielding device can also be other structures, as long as it can shield external interfering magnetic fields.

[0071] Optionally, the chromatography detection device further includes a transmission mechanism 8 and a second clamp provided on the transmission mechanism 8. The second clamp is used to clamp the measurement carrier 2, and the transmission mechanism 8 is used to input or output the measurement carrier 2 to or from the moving mechanism 5. Through the cooperation of the transmission mechanism 8 and the second clamp, the measurement carrier 2 is moved into or out of the moving mechanism 5. Further, as Figure 8 shown, the transmission mechanism 8 can be a conveyor belt. The transmission mechanism 8 can also be a robotic arm, or other mechanisms, as long as it can move the measurement carrier 2 into or out of the moving mechanism 5. Of course, the driving member 51 of the transmission mechanism 8 can be a motor, a cylinder, a hydraulic cylinder, or other driving structures, as long as it can achieve a driving effect. In this embodiment, the transmission mechanism 8 is a robotic arm, which is flexible to move. Optionally, the second clamp can be a jaw, a buckle, or other structures, as long as it can clamp and release the measurement carrier 2. Further, the second clamp can be loosened and tightened manually, with low cost, and the second clamp can also be loosened and tightened electrically to achieve full-automatic detection.

[0072] The present invention also provides a chromatography detection method, which uses the above-mentioned chromatography detection device to achieve quantitative detection of the target content in the test body. Using this detection method, the detection process is fast and the accuracy is high. The chromatography detection method includes:

[0073] The magnetic sensitive particles 1 attached with the binding substance are fully mixed with the sample to be tested, and the binding substance is used to specifically bind to the target;

[0074] A mixture of the magnetic sensitive particles 1 and the object to be tested is dropped onto the sample pad of the measuring carrier 2, and the magnetic sensitive particles 1 move toward the test position, which is used for specific binding with the target object;

[0075] Magnetizing the magnetic sensitive particles 1 on the measuring carrier 2 so that the magnetic field directions of the magnetic sensitive particles 1 are consistent;

[0076] The measuring carrier 2 is moved to drive the test position to move, so as to periodically change the magnetic field component detected by the magnetic field measuring mechanism 4 of the magnetic sensitive particles 1 at the test position;

[0077] The magnetic field strength at the test position is measured by the magnetic field measuring mechanism 4 to detect the target object.

[0078] The chromatographic detection method determines the content of the target object in the test object by lateral chromatography and measuring the magnetic field intensity of the magnetized magnetic sensitive particles 1 at the test position.

[0079] Specifically, in this embodiment, the preparation of the mixture of the magnetic sensitive particle 1 and the object to be detected specifically includes the antibody coupling and immune reaction of the magnetic sensitive particle 1. First, the magnetic sensitive particle 1 can capture the antibody to be coupled by a "one-step method" or a "two-step method" according to the functional groups modified on the surface. The amount of antibody coupled to the magnetic sensitive particle 1 can range from 10 to 50 ug / mg. The coupled magnetic sensitive particle 1 can be washed and blocked and stored in a magnetic sensitive particle 1 storage solution for long-term use. Optionally, the washing solution includes a salt buffer and a non-ionic surfactant, and the blocking solution includes animal serum. Then, an immune reaction is performed, and a certain amount of magnetic sensitive particles 1 coupled with antibodies are taken, washed with a buffer solution, and mixed and incubated with the object to be detected to form a mixture.

[0080] Optionally, the measurement carrier 2 is moved to drive the test position to move, so as to periodically change the magnetic field component detected by the magnetic field measuring mechanism 4 of the magnetic sensitive particles 1 at the test position. Specifically, the following four methods can be used:

[0081] The measuring carrier 2 is rotated to drive the test position to rotate, and the rotation axis is staggered with the measurement center of the magnetic field measuring mechanism 4 to ensure that the distance and magnetic field direction of the magnetic sensitive particles 1 at the test position relative to the magnetic field measuring mechanism 4 are changed.

[0082] Alternatively, the measuring carrier 2 is linearly reciprocated to drive the test position to linearly reciprocate, and the path of the test position during the linear reciprocation is offset from the measurement center of the magnetic field measuring mechanism 4, so as to ensure that both the distance and the magnetic field direction of the magnetosensitive particles 1 at the test position relative to the magnetic field measuring mechanism 4 are changed.

[0083] Alternatively, the measuring carrier 2 is linearly reciprocated to drive the test position to linearly reciprocate, and the path of the test position during the linear reciprocation is collinear with the measurement central axis of the magnetic field measuring mechanism 4 and the magnetic field direction of the magnetosensitive particles 1 at the test position is not perpendicular to the path of the test position. If the path of the test position is collinear with the measurement central axis of the magnetic field measuring mechanism 4 and the magnetic field direction of the magnetosensitive particles 1 at the test position is perpendicular to the path of the test position, the magnetic field component measured by the magnetic field measuring mechanism 4 is zero. If it is not perpendicular, both the distance and the magnetic field direction of the magnetosensitive particles 1 at the test position relative to the magnetic field measuring mechanism 4 are changed.

[0084] Alternatively, the measuring carrier 2 is non-linearly reciprocated to drive the test position to non-linearly reciprocate, so as to ensure that both the distance and the magnetic field direction of the magnetosensitive particles 1 at the test position relative to the magnetic field measuring mechanism 4 are changed.

[0085] Optionally, the period of the change in the magnetic field component detected by the magnetic field measuring mechanism 4 for the magnetosensitive particles 1 at the test position is T. After measuring the magnetic field intensity at the test position by the magnetic field measuring mechanism 4, it further includes: demodulating and analyzing the magnetic field signal detected by the magnetic field measuring mechanism 4 to obtain a signal with a period of T for detecting the target object.

[0086] Optionally, after lateral chromatography is completed, only the test position on the measuring carrier 2 is retained, and then the magnetic field at the test position is detected. Retaining only the test position on the measuring carrier 2 can accurately measure the target object and avoid interference from other parts on the measuring carrier 2.

[0087] Preferably, the specific steps of the chromatography detection method provided in this embodiment include:

[0088] S1: The magnetosensitive particles 1 attached with the conjugate are fully mixed with the test sample, and the conjugate is used for specifically binding to the target object;

[0089] S2: The measuring carrier 2 is sequentially provided with a sample pad, a test line 21 and a quality control line 22 along the chromatography direction. The mixture of the magnetosensitive particles 1 and the test sample is dropped on the sample pad of the measuring carrier 2, and the test line 21 is used for specifically binding to the target object;

[0090] S3: The measuring carrier 2 is placed on the second fixture, the transmission mechanism 8 is driven to operate, the measuring carrier 2 is moved to the turntable, and the measuring carrier 2 is located at the center of the uniform region of the magnetic field magnetization mechanism 3;

[0091] S4: Turn on the signal generator of the magnetic field magnetization mechanism 3. According to the properties of the magnetic sensitive particles 1, including: type, particle size, sample droplet volume, etc., set the matching modulation frequency, magnetic field strength, and magnetization time. The modulation frequency is generally between 5 - 100 Hz, the modulation field size is less than 1 T, and the magnetization time is controlled at about 1 minute.

[0092] S5: Magnetize the magnetic sensitive particles 1 on the measurement carrier 2 to make the magnetic field directions of the magnetic sensitive particles 1 at the test line 21 consistent, and make the magnetic field direction of the magnetic sensitive particles 1 at the quality control line 22 collinear with the quality control line 22.

[0093] S6: After magnetization, continue to drive the transmission mechanism 8 to operate, move the measurement carrier 2 to the first fixture on the turntable and clamp it for fixation. Then drive the motor to work, rotate the measurement carrier 2 around the quality control line 22 at the same frequency as the modulation of the magnetic field of the magnetic sensitive particles 1, and drive the magnetic sensitive particles 1 to rotate, so as to periodically change the magnetic field component detected by the magnetic field measurement mechanism 4 at the test line 21.

[0094] S7: Measure the magnetic field strength of the test line 21 through the magnetic field measurement mechanism 4. Specifically, after the moving mechanism 5 rotates smoothly, turn on the magnetic force probe to detect the magnetic field, measure the magnetic field strength of the magnetized magnetic sensitive particles 1 at the test position, and drive the signal acquisition and processing unit to collect the magnetic field signal.

[0095] S8: Demodulate and analyze the magnetic field signal detected by the magnetic field measurement mechanism 4 to obtain a signal with a rotation period of T for detecting the target object.

[0096] Step S6 specifically further includes staggering the measurement center of the magnetic field measurement mechanism 4 from the quality control line 22, that is, staggering the measurement center from the rotation axis, ensuring that the distance and magnetic field direction between the magnetic sensitive particles 1 at the test line 21 and the magnetic field measurement mechanism 4 change, and thus periodically changing the magnetic field component detected by the magnetic field measurement mechanism 4 at the test line 21.

[0097] In addition, after step S2 and before step S3, there is also step S21: Cut off the quality control line 22 of the lateral chromatographic test strip. The magnetic sensitive particles 1 without attached target objects stay at the quality control line 22. Cut off the quality control line 22 on the lateral chromatographic test strip to eliminate the interference of the magnetic sensitive particles 1 without attached target objects on the magnetic field strength measurement, improve the accuracy of the magnetic field strength measurement of the magnetic sensitive particles 1 with attached target objects, and thus improve the accuracy of the target object content detection.

[0098] Obviously, the above-mentioned embodiments of the present invention are merely examples for clearly illustrating the present invention, rather than limitations on the implementation manners of the present invention. For those of ordinary skill in the art, various obvious changes, re-adjustments and substitutions can be made without departing from the protection scope of the present invention. It is not necessary and impossible to enumerate all implementation manners here. Any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention shall be included within the protection scope of the claims of the present invention.

Claims

1. A chromatographic detection device, characterized in that, it includes: Magnetic sensitive particles (1), with a conjugate for specifically binding to a target attached thereto; A measurement carrier (2), which is sequentially provided with a sample pad and a test position along the chromatographic direction. The sample pad is used to hold the magnetic sensitive particles (1) and a test sample containing the target, and the test position is used to capture the target; A magnetic field magnetization mechanism (3), which is used to magnetize the magnetic sensitive particles (1) at the test position so that the magnetic field directions of the magnetic sensitive particles (1) at the test position are consistent; A magnetic field measurement mechanism (4), which is used to measure the magnetic field strength of the magnetized magnetic sensitive particles (1) at the test position to obtain the content of the target in the test sample; A moving mechanism (5), the measurement carrier (2) is arranged on the moving mechanism (5), and the moving mechanism (5) is used to periodically change the magnetic field component of the magnetic sensitive particles (1) at the test position detected by the magnetic field measurement mechanism (4).

2. The chromatographic detection device according to claim 1, characterized in that, the moving mechanism (5) is used to periodically change the distance or magnetic field direction of the magnetic sensitive particles (1) at the test position relative to the magnetic field measurement mechanism (4).

3. The chromatographic detection device according to claim 2, characterized in that, the measurement carrier (2) is a lateral flow test strip, and a test line (21) and a quality control line (22) are provided on the lateral flow test strip. The test line (21) serves as the test position, and the quality control line (22) is used to verify the validity of the chromatographic result.

4. The chromatographic detection device according to claim 3, characterized in that, when the moving mechanism (5) operates, the magnetic field component of the magnetic sensitive particles (1) at the quality control line (22) detected by the magnetic field measurement mechanism (4) remains unchanged.

5. The chromatographic detection device according to claim 4, characterized in that, the moving mechanism (5) is a rotating mechanism, and the rotation axis of the rotating mechanism is offset from the measurement center of the magnetic field measurement mechanism (4); the rotation axis of the rotating mechanism coincides with the quality control line (22); the magnetic field magnetization mechanism (3) is further used to magnetize the magnetic sensitive particles (1) at the quality control line (22) so that the magnetic field directions of the magnetic sensitive particles (1) at the quality control line (22) are consistent, and the magnetic field direction of the magnetic sensitive particles (1) at the quality control line (22) is collinear with the rotation axis of the rotating mechanism.

6. The chromatographic detection device according to any one of claims 1-5, characterized in that, the chromatographic detection device further includes a magnetic flux concentrator (6), which is used to concentrate the magnetic field lines of the magnetized magnetic sensitive particles (1) to the magnetic field measurement mechanism (4).

7. The chromatographic detection device according to any one of claims 1-5, characterized in that, The tomography detection device further comprises a magnetic shielding mechanism (7) for shielding an external interfering magnetic field; the magnetic shielding mechanism (7) is provided with an inner cavity, and the measurement carrier (2), the magnetic field magnetization mechanism (3) and the magnetic field measurement mechanism (4) are all located in the inner cavity.

8. A chromatography detection method, It is characterized in that include: Fully mixing the magnetic sensitive particles (1) attached with a binding substance with the test object, wherein the binding substance is used to specifically bind to the target object; Dropping a mixture of the magnetically sensitive particles (1) and the object to be tested onto a sample pad of a measuring carrier (2), the magnetically sensitive particles (1) move toward a test position, and the test position is used to specifically bind to the target object; Magnetizing the magnetically sensitive particles (1) on the measuring carrier (2) so that the directions of the magnetic fields of the magnetically sensitive particles (1) are consistent; The measuring carrier (2) is moved to drive the test position to move, so as to periodically change the magnetic field component of the magnetic sensitive particles (1) at the test position detected by the magnetic field measuring mechanism (4); The magnetic field intensity at the test position is measured by the magnetic field measuring mechanism (4) to detect the target object.

9. The chromatography detection method according to claim 8, It is characterized in that The method of moving the measuring carrier (2) to drive the test position to move so as to periodically change the magnetic field component detected by the magnetic field measuring mechanism (4) of the magnetic sensitive particles (1) at the test position comprises: The measuring carrier (2) is caused to rotate so as to drive the test position to rotate, and the rotation axis is offset from the measuring center of the magnetic field measuring mechanism (4); or, The measuring carrier (2) is caused to move in a linear reciprocating translational motion to drive the test position to move in a linear reciprocating translational motion, and the path of the test position during the linear reciprocating translational motion is staggered with the measurement center of the magnetic field measuring mechanism (4); or, The measuring carrier (2) is caused to perform linear reciprocating translational motion, thereby driving the test position to perform linear reciprocating translational motion, and the path of the test position during the linear reciprocating translation is collinear with the measurement center axis of the magnetic field measuring mechanism (4), and the magnetic field direction of the magnetically sensitive particles (1) at the test position is not perpendicular to the path of the test position.

10. The chromatography detection method according to claim 8, It is characterized in that The magnetic field component variation period of the magnetic sensitive particles (1) at the test position detected by the magnetic field measuring mechanism (4) is T; The tomographic detection method further comprises demodulating and analyzing the magnetic field signal detected by the magnetic field measurement mechanism (4) to obtain a signal with a period of T for detecting the target object.

11. The chromatography detection method according to claim 8, It is characterized in that The tomography detection method further comprises retaining only the test position on the measurement carrier (2) after completing the lateral tomography, and then detecting the magnetic field at the test position.

12. The chromatography detection method according to any one of claims 8 to 11, It is characterized in that The measurement carrier (2) is successively provided with the sample pad, the test line (21) and the quality control line (22) along the chromatographic direction. The mixture of the magnetic particles (1) and the analyte is dropped onto the sample pad of the measurement carrier (2). The test line (21) is used for specifically binding to the target substance; After lateral chromatography is completed, the magnetic particles (1) on the measurement carrier (2) are magnetized so that the magnetic field directions of the magnetic particles (1) at the test line (21) are consistent, and the magnetic field direction of the magnetic particles (1) at the quality control line (22) is collinear with the quality control line (22); The measurement carrier (2) is rotated with the quality control line (22) as the rotation axis to periodically change the magnetic field component of the magnetic particles (1) at the test line (21) detected by the magnetic field measurement mechanism (4); The magnetic field strength of the test line (21) is measured by the magnetic field measurement mechanism (4); The magnetic field signal detected by the magnetic field measurement mechanism (4) is demodulated and analyzed to obtain a signal with a rotation period of T for detecting the target substance.

13. According to the chromatographic detection method described in claim 12, it is characterized in that the measurement center of the magnetic field measurement mechanism (4) is offset from the quality control line (22).

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