CN117434141A

CN117434141A - Sample detection method, device, computer equipment and storage medium

Info

Publication number: CN117434141A
Application number: CN202311329407.4A
Authority: CN
Inventors: 王伯宇; 蒋志远; 彭涛; 屈继峰
Original assignee: National Institute of Metrology
Current assignee: National Institute of Metrology
Priority date: 2023-10-13
Filing date: 2023-10-13
Publication date: 2024-01-23

Abstract

The present application relates to a sample detection method, apparatus, computer device, storage medium and computer program product. The method comprises the following steps: controlling a linear transmission device to transmit the target sample to the direction of the magnetic field measurement device; acquiring the magnetic field intensity of the target sample at each moment measured by the magnetic field measuring device in the transmission process of the target sample; acquiring the transmission time length of a target sample through a linear transmission device; determining a magnetic field intensity and transmission displacement curve aiming at the target sample according to the magnetic field intensity and transmission time length of the target sample at each moment; the number of magnetic markers in the specific binding region of the target sample is determined based on the magnetic field strength versus transmission displacement curve. By adopting the method, the accuracy of quantitative calculation of the magnetic markers in the target sample is improved.

Description

Sample detection method, device, computer equipment and storage medium

Technical Field

The present application relates to the field of biomedical technology, and in particular, to a sample detection method, apparatus, computer device, storage medium, and computer program product.

Background

With the development of biomedical technology, rapid, accurate and reliable diagnostic techniques are becoming increasingly important. As a rapid detection tool, the immunochromatographic test paper has the advantages of convenience, high efficiency and the like, and has become an important means for biomedical detection. At present, researchers at home and abroad introduce magnetic nanoparticle (Magnetic nanoparticles, MNPs) probes into an immunochromatographic test paper detection technology, and a magnetic nanoparticle-marked immunochromatographic test paper detection technology is provided.

At present, the immunochromatography test paper detection technology marked by magnetic nano particles is based on the characteristics of quantum size effect, surface effect, small size effect, paramagnetic property and the like of the magnetic nano particles, and is combined with the immunochromatography technology (IA), so that the immunochromatography test paper detection technology has the advantages of rapidness, accuracy, high sensitivity, low cost and the like. Not only can the sensitivity and the specificity of detection be improved, but also a relatively accurate quantitative detection result can be provided.

However, in the existing immunochromatographic test paper detection technology of magnetic nanoparticle labels, the electric signal is often used as an intermediate bridge, electromagnetic signals are converted for multiple times through a complex algorithm, and uncertainty of a quantitative calculation process of the magnetic markers is increased, so that the accuracy of quantitative detection of the existing immunochromatographic test paper detection technology of magnetic nanoparticle labels is low.

Disclosure of Invention

In view of the foregoing, it is desirable to provide a sample detection method, apparatus, computer device, computer-readable storage medium, and computer program product that can improve the accuracy of quantitative detection of magnetic nanoparticles in a sample.

In a first aspect, the present application provides a sample detection method, applied to a data processing device in a sample detection system, the sample detection system further including a magnetic field measurement device and a linear actuator, including:

Controlling the linear transmission device to transmit the target sample to the direction of the magnetic field measurement device;

acquiring the magnetic field intensity of the target sample at each moment and the transmission time length of the target sample, which are measured by the magnetic field measuring device, in the transmission process of the target sample;

determining a magnetic field intensity and transmission displacement curve aiming at the target sample according to the magnetic field intensity of the target sample at each moment and the transmission time length;

and determining the number of the magnetic markers in the specific binding region of the target sample based on the magnetic field strength and transmission displacement curve.

In one embodiment, the magnetic field measuring device includes an atomic magnetometer and a magnetic shielding cylinder, the magnetic shielding cylinder is used for shielding magnetic field influence of geomagnetism on the atomic magnetometer, the atomic magnetometer is arranged in the magnetic shielding cylinder, and is used for acquiring magnetic field intensity generated by the target sample in real time and transmitting the magnetic field intensity generated by the target sample at each moment to the data processing device, and the controlling the linear transmission device transmits the target sample to the direction of the magnetic field measuring device includes:

And controlling the linear transmission device to transmit a target sample to the magnetic shielding barrel, and transmitting the target sample into the magnetic shielding barrel so that the target sample passes through the atomic magnetometer in the magnetic shielding barrel.

In one embodiment, the determining the number of magnetic markers in the specific binding region of the target sample based on the magnetic field strength versus transmission displacement curve comprises:

determining a relationship curve of the specific binding position of the target sample and the magnetic field intensity based on the magnetic field intensity and the transmission displacement curve;

determining the number of magnetic markers in the specific binding region of the target sample based on the relationship between the specific binding position of the target sample and the magnetic field strength.

In one embodiment, the determining the magnetic field strength versus transmission displacement curve for the target sample according to the magnetic field strength of the target sample at each moment and the transmission time length includes:

determining the horizontal transmission displacement of the target sample according to the preset motion speed and the transmission time length of the target sample;

and determining a magnetic field intensity and transmission displacement curve aiming at the target sample according to the magnetic field intensity of the target sample at each moment and the horizontal transmission displacement.

In one embodiment, the determining the specific binding position versus magnetic field strength curve of the target sample based on the magnetic field strength versus transmission displacement curve includes:

setting the transmission displacement corresponding to the maximum value of the magnetic field intensity in the curve of the magnetic field intensity and the transmission displacement as a displacement zero point;

and determining a relation curve of the specific binding position of the target sample and the magnetic field intensity according to the transmission displacement corresponding to the displacement zero point and the magnetic field intensity and transmission displacement curve.

In one embodiment, the determining the number of magnetic markers in the specific binding region of the target sample based on the specific binding position of the target sample versus the magnetic field strength comprises:

determining a target magnetization of a specific binding region of the target sample based on a plot of specific binding position of the target sample versus magnetic field strength, and a magnetic field calculation parameter;

determining the number of magnetic markers in the specific binding region of the target sample based on the target magnetization and the magnetic marker calculation parameters in the specific binding region of the target sample.

In one embodiment, the magnetic field calculation parameters include a background magnetic field, a vacuum permeability, and a perpendicular distance of an atomic magnetometer from the target sample, and the determining the target magnetization of the specific binding region of the target sample based on the specific binding position of the target sample versus the magnetic field strength, and the magnetic field calculation parameters comprises:

and fitting the relation curve of the specific binding position of the target sample and the magnetic field intensity based on the relation curve of the specific binding position of the target sample and the magnetic field intensity, the vertical distance between the atomic magnetometer and the target sample, the transmission displacement corresponding to the maximum value of the magnetic field intensity and the horizontal transmission displacement of the target sample, and determining the target magnetization of the specific binding region of the target sample.

In one embodiment, the magnetic marker calculation parameter includes a density of magnetic nanoparticles in the target sample, a volume of the magnetic nanoparticles, and a saturation magnetization of the magnetic nanoparticles, and the determining the number of magnetic markers in the specific binding region of the target sample based on the target magnetization, the magnetic marker calculation parameter in the specific binding region of the target sample includes:

Determining a magnetization parameter based on a density of magnetic nanoparticles in the target sample, a volume of the magnetic nanoparticles, and a saturation magnetization of the magnetic nanoparticles, the magnetization parameter being positively correlated to the density of the magnetic nanoparticles, the volume of the magnetic nanoparticles, and the saturation magnetization of the magnetic nanoparticles in the target sample;

determining the number of magnetic markers in the specific binding region of the target sample based on the magnetization parameter and the target magnetization, the number of magnetic markers being inversely related to the magnetization parameter and the number of magnetic markers being positively related to the target magnetization.

In a second aspect, the present application also provides a sample detection device comprising:

the control module is used for controlling the linear transmission device to transmit the target sample to the direction of the magnetic field measurement device;

the acquisition module is used for acquiring the magnetic field intensity of the target sample at each moment and the transmission time length of the target sample, which are measured by the magnetic field measuring device, in the transmission process of the target sample;

the first determining module is used for determining a magnetic field intensity and transmission displacement curve aiming at the target sample according to the magnetic field intensity of the target sample at each moment and the transmission time length;

And the second determining module is used for determining the number of the magnetic markers in the specific binding region of the target sample based on the magnetic field intensity and transmission displacement curve.

In one embodiment, the control module is specifically configured to:

In one embodiment, the second determining module is specifically configured to:

In one embodiment, the first determining module is specifically configured to:

In one embodiment, the second determining module is specifically configured to:

In one embodiment, the magnetic field calculation parameters include a background magnetic field, a vacuum permeability, and a perpendicular distance of the atomic magnetometer from the target sample, and the second determining module is specifically configured to:

In one embodiment, the magnetic marker calculation parameter comprises a density of magnetic nanoparticles in the target sample, a volume of the magnetic nanoparticles, and a saturation magnetization of the magnetic nanoparticles, and the second determination module is specifically configured to:

In a third aspect, the present application also provides a computer device comprising a memory and a processor, the memory storing a computer program, the processor implementing the following steps when executing the computer program:

In a fourth aspect, the present application also provides a computer readable storage medium having stored thereon a computer program which when executed by a processor performs the steps of:

In a fifth aspect, the present application also provides a computer program product comprising a computer program which, when executed by a processor, performs the steps of:

The sample detection method, the device, the computer equipment, the storage medium and the computer program product are applied to a data processing device in a sample detection system, and the sample detection system also comprises a magnetic field measuring device and a linear transmission device, and the target sample is transmitted to the direction of the magnetic field measuring device by controlling the linear transmission device; acquiring the magnetic field intensity of the target sample at each moment measured by the magnetic field measuring device in the transmission process of the target sample; acquiring the transmission time length of the target sample through the linear transmission device; determining a magnetic field intensity and transmission displacement curve aiming at the target sample according to the magnetic field intensity of the target sample at each moment and the transmission time length; and determining the number of the magnetic markers in the specific binding region of the target sample based on the magnetic field strength and transmission displacement curve. By adopting the method, the relation curve between the specific binding position of the antigen and the antibody of the target sample and the magnetic field intensity can be determined based on the magnetic field intensity of the target sample at each moment and the transmission time of the target sample, and then the number of the magnetic markers in the specific binding region of the target sample can be quantitatively detected according to the relation curve between the specific binding position of the antigen and the antibody and the magnetic field intensity. Because the conversion of electromagnetic signals for multiple times is not needed, errors caused in the quantitative calculation process of the magnetic markers due to the fact that the electromagnetic signals are converted for multiple times by a complex algorithm can be avoided, and therefore accuracy of quantitative calculation of the magnetic markers in a target sample is improved.

Drawings

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the related art, the drawings that are required to be used in the embodiments or the related technical descriptions will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and other drawings may be obtained according to the drawings without inventive effort for a person having ordinary skill in the art.

FIG. 1 is a diagram of an application environment of a sample detection method in one embodiment;

FIG. 2 is a flow chart of a sample detection method according to one embodiment;

FIG. 3 is a schematic diagram of a detection schematic of a sample detection method according to one embodiment;

FIG. 4 is a schematic diagram of a sample detection system according to one embodiment;

FIG. 5 is a schematic diagram of the principle of operation of an atomic magnetometer in one embodiment;

FIG. 6 is a schematic diagram of the structure of an atomic magnetometer in one embodiment;

FIG. 7 is a schematic flow chart of determining the amount of magnetic markers in a specific binding region of a target sample in one embodiment;

FIG. 8 is an exemplary schematic diagram of a specific binding site versus magnetic field strength for a target sample in one embodiment;

FIG. 9 is a flow chart of determining a magnetic field strength versus drive displacement curve for a target sample in one embodiment;

FIG. 10 is a flow chart of determining the specific binding site of a target sample versus the magnetic field strength in one embodiment;

FIG. 11 is a schematic flow chart of another embodiment of determining the amount of magnetic markers in a specific binding region of a target sample;

FIG. 12 is a schematic flow chart of another embodiment of determining the amount of magnetic markers in a specific binding region of a target sample;

FIG. 13 is a schematic diagram showing the detection results of immunochromatographic strips for different concentrations of carcinoembryonic antigen in one embodiment;

FIG. 14 is a graphical representation of CEA concentration targets versus magnetization M values in one embodiment;

FIG. 15 is a flow chart of the magnetic field strength ratio (MIt/c) versus the logarithm of the concentration in another embodiment;

FIG. 16 is a block diagram of a sample detection device in one embodiment;

fig. 17 is an internal structural view of a computer device in one embodiment.

Detailed Description

In order to make the objects, technical solutions and advantages of the present application more apparent, the present application will be further described in detail with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the present application.

Before describing the embodiments of the present invention, the technical terms involved in the present invention will be explained:

immunochromatography: the principle of immunochromatography (immunochromatography) is to fix a specific antibody to a certain zone of a nitrocellulose membrane, after one end of the dried nitrocellulose is immersed in a sample (urine or serum), the sample moves forward along the membrane due to capillary action, and when the sample moves to a zone where the antibody is fixed, the corresponding antigen in the sample is specifically combined with the antibody, and if the zone is stained with immune colloidal gold or immune enzyme, the zone can display a certain color, thereby realizing specific immunodiagnosis.

Tesla: english is tesla, the symbol is T, and the unit is derived from the international unit of magnetic flux density or magnetic induction intensity.

Magnetization: refers to a phenomenon that under the action of a magnetic field, the orientation tends to be consistent when magnetic moments in a material are aligned, so that certain magnetism is presented.

Residual magnetization: the residual magnetic flux density/magnetic field intensity is Br, which means that after the magnet is magnetized to saturation, the external magnetic field is removed, and the original external magnetic field can still keep a certain magnetization intensity. The limit value of remanence is the saturation magnetization.

Circularly polarized light: the light that rotates the electric vector end point to trace the circular track is called circularly polarized light, which is a special case of elliptically polarized light. When the propagation directions are the same, the two plane polarized lights with the vibration directions being mutually perpendicular and the phase difference being constant phi= (2 m plus or minus 1/2) pi are overlapped, and then circularly polarized lights with regularly changing electric vectors can be synthesized.

Pumping: pumping is a process that uses light to raise (or "pump") electrons from a lower energy level in an atom or molecule to a higher energy level.

Linearly polarized light: in the propagation direction of light, the light vector vibrates in only one fixed direction, and this light is called plane polarized light, and the trajectory of the light vector end point is a straight line, which is also called linearly polarized light.

Alkali metal atomic gas cell: the alkali metal atomic gas chamber is a core component for inertial measurement and ultrasensitive magnetic field measurement, and is generally called atomic gas chamber for short. In ultrasensitive magnetic field measurement applications, an optical pumping technology is generally used to polarize atoms in a gas chamber, and at the same time, thermal motions of the atoms and various collisions may destroy the polarization state of the atoms, so that the atoms undergo depolarization and are restored to a Boltzmann (Boltzmann) distribution state. The time required for this process is commonly referred to as the spin relaxation time, which is one of the key indicators of the performance of an alkali metal atomic gas cell. The glass shell material, surface shape accuracy, the state of the inner wall of the gas chamber, the gas filling ratio and the like of the alkali metal atom gas chamber are also important factors influencing the performance of the gas chamber.

PEEK: polyether-ether-ketone (PEEK) can be used as a high-temperature-resistant structural material and an electrical insulation material, and can be compounded with glass fibers or carbon fibers to prepare a reinforcing material.

CEA: carcinoembryonic antigen (carcinoembryonic antigen, CEA), an acidic glycoprotein with human embryonic antigen properties, is often used as a specific biological recognition element for early diagnosis of colon and rectal cancer.

Magnetic field strength conversion: 10 ³ Femtosla (fT) =1 picotesla (nT) =10 ^-3 Naltesla (pT) =10 ^-6 Microtesla (μt) =10 ^-9 Millitesla (mT) =10 ^-12 Tesla (T).

Mass conversion: 1 nanogram (ng) =10 ^-3 Micrograms (μg) =10 ^-6 Milligrams (mg) =10 ^-9 Gram (g).

The traditional immunochromatography test paper detection method can only perform qualitative detection of the marker, cannot provide an accurate quantitative result (for example, an optical colorimetry detection result can only be qualitative, color discrimination can be different under different environments, the accuracy is to be improved, a fluorescence method needs longer reaction time and higher reagent cost, the generated data is relatively complex, and the difficulty of data processing and interpretation is increased), so that the application of the immunochromatography test paper detection method in future intelligent clinical diagnosis and treatment is limited. In order to overcome the limitation, researchers at home and abroad introduce magnetic nanoparticle probes into immunochromatography test paper detection technology, and put forward a magnetic nanoparticle labeled immunochromatography test paper detection technology, which is based on the quantum size effect, the surface effect, the small size effect, the magnetism order and other characteristics of magnetic nanoparticles, is combined with the immunochromatography technology, has the advantages of rapidness, accuracy, high sensitivity, low cost and the like, can improve the sensitivity and the specificity of detection, is expected to provide relatively accurate quantitative results, and is currently applied to the fields of biomedicine, environmental monitoring, food safety and the like.

With the development of intelligent diagnosis and treatment technology, quantitative detection has important significance for improving the accuracy of clinical diagnosis, promoting biological research and improving drug development, as it can provide more accurate and reliable results. In addition, the accurate quantitative research of the magnetic markers can effectively promote the deep understanding of the structure and principle of the immunochromatography test paper and the exploration of the interaction mechanism of the markers and the antibodies.

The existing optical detection method has more defects, such as that the optical colorimetric method can only detect signals on the surface layer of the specific binding region of the immunochromatographic test paper and has lower sensitivity; in the research of the existing detection device for magnetic measurement immunochromatography test paper, the detection device comprises a detection device body: johnson et al selected magnetic nanoparticles as markers, and detected breast cancer cells with 105 cells using SQUID (superconducting quantum interference device, superconducting quantum interferometer). The detection of IAV (influenza A virus) nucleoprotein (viral ribonucleoprotein, NP) and purified H3N2 (influenza A H3N2 virus) v was achieved by Yuan et al using GMR (Giant Magneto Resistive, giant magneto resistance magnetic field sensor) based immunodetection device with minimum detection limits of 15ng/mL and 125TCID (Tissue culture infective dose, half tissue culture infectious dose) 50/mL, respectively. Cheng et al detected a chromatographic strip containing Parvalbumin by MAR (hybrid anti-globulin reaction assay) with a minimum detection limit of 0.046. Mu.g/mL; orlov et al realized detection of BoNT-A (botulinum subtype A), boNT-B (botulinum subtype B) and BoNT-E (botulinum subtype E) according to the non-linear magnetization mechanism of the superparamagnetic nanoparticles, with minimum detection limits of 0.20ng/mL, 0.12ng/mL and 0.35ng/mL, respectively. The detection of Potato virus X (Potato virus X) by Rettcher et al was carried out using a magnetic nanoparticle quantitative reader with a minimum detection limit of 56ng/mL. However, the above methods all have respective drawbacks, such as: SQUID needs to operate at low temperature, and magnetic field of the magnetic marker in the test paper is not uniformly distributed in space, and magnetic flux detected by SQUID is often limited by geometric parameters of a measurement system; huge magnetic resistance sensor volume, the data acquisition process is loaded down with trivial details; immunochromatography analyzers (based on the influence of magnetic nanoparticles on magnetic flux) are simple in structure, but are not mature enough in coil geometry and detection mode; magnetic nanoparticle quantitative readers (based on mixing techniques) rely entirely on the properties of the superparamagnetic nanoparticles, and thus the development of corresponding superparamagnetic nanoparticles alone is required. In addition, the existing magnetic sensor cannot realize accurate quantitative detection of a sample to be detected.

The sample detection method provided by the embodiment of the application can be applied to a data processing device in a sample detection system shown in fig. 1, and the sample detection system further comprises a magnetic field measuring device and a linear transmission device.

Wherein the magnetic field measuring device can be electrically or communicatively connected to the data processing device, and the linear actuator can be electrically or communicatively connected to the data processing device.

The data processing device is a computer terminal having a function of collecting data and analyzing the data, and may be constituted by two devices such as a data collecting device and a computer terminal. The data processing device is used for collecting and recording the numerical value of the residual magnetization intensity (Br) detected by the magnetic field measuring device. The format of the data record table for recording data may be: the first column is the acquisition time and the second column is the residual magnetization (Br) of the sample to be measured obtained by detection.

The linear transmission device is used for linearly transmitting a sample to be measured into the magnetic field measuring device at a certain speed at a constant speed, the linear transmission device comprises a mechanical transmission part and an electronic control part, the mechanical transmission part is used for completing transmission of a target sample, the mechanical transmission part consists of an electric displacement table (stepping motor) and a quartz rod with a sample support, and the mechanical transmission part is used for moving an LFIA (immunochromatography test) test strip with magnetic nano particles (namely the target sample) along a single direction. The electronic control part is used for receiving transmission instructions, such as forward/backward movement instructions, speed change instructions and the like, sent by the data processing device, and realizing accurate control of the movement through the control unit.

In an exemplary embodiment, as shown in fig. 2, a sample detection method is provided, and the method is applied to the data processing apparatus in fig. 1, for example, and includes the following steps 202 to 208. Wherein:

step 202, controlling the linear driving device to drive the target sample to the direction of the magnetic field measuring device.

The method comprises the steps that a target sample is a chromatographic test strip, and in order to avoid the large influence of the residual magnetic field of a magnetic marker in a non-specific binding area on the total residual magnetic field, the target sample is pretreated, namely a ceramic scraper is used for scraping a nitrocellulose membrane in the non-specific binding area of the immunochromatographic test strip, so that only the binding position is leaked; and then the pretreated immunochromatographic test paper is placed in an electromagnet for magnetization for 1-3 minutes, and the test paper is tightly attached to the surface of the electromagnet. The target sample is fixed on a miniature sample frame made of PEEK in advance, and the sample frame is fixed on a quartz glass rod connected with a linear transmission device.

A schematic diagram of the sample detection method provided in the embodiment of the present application may be shown in fig. 3, where,

In this embodiment, the data processing device may obtain a preset transmission speed, for example, the preset transmission speed may be between 0.1 and 30 mm/s.

Then, the data processing device generates a control instruction according to the preset transmission speed, and sends the control instruction to the linear transmission device, so that the linear transmission device is controlled to drive the target sample at the preset transmission speed, and the target sample is linearly driven at a constant speed in the direction of the magnetic field measuring device.

Step 204, acquiring the magnetic field intensity of the target sample at each moment and the transmission time length of the target sample, which are measured by the magnetic field measuring device in the transmission process of the target sample.

In the embodiment of the application, the data processing device is connected with the magnetic field measuring device and can receive the magnetic field intensity of the target sample measured by the magnetic field measuring device at each moment in the transmission process.

The data processing device may then acquire the transmission duration of the target sample. Specifically, the data processing device may record the time when the transmission starts when the linear transmission device starts the transmission of the target sample, record the time when the linear transmission device ends the transmission of the target sample, and record the time when the transmission ends, thereby obtaining the transmission duration of the target sample. Optionally, the data processing device may further calculate a transmission duration of the target sample according to the horizontal transmission displacement of the target sample and a preset transmission speed of the target sample.

The process of obtaining the transmission time length of the target sample is not particularly limited in the embodiments of the present application.

Step 206, determining a magnetic field strength and transmission displacement curve for the target sample according to the magnetic field strength and transmission time length of the target sample at each moment.

In the embodiment of the application, the data processing device determines a magnetic field intensity and transmission displacement curve aiming at the target sample according to the magnetic field intensity and transmission time length of the target sample at each moment.

Specifically, the data processing device can display a relationship curve of the magnetic field strength and the transmission time of the target sample in real time according to the magnetic field strength and the transmission time of the target sample at each moment through LabVIEW (a program development environment which is specially designed for the application requiring testing, measuring and controlling).

Then, the data processing device determines a magnetic field intensity and transmission displacement curve aiming at the target sample according to a relation curve of the magnetic field intensity and transmission time of the target sample and a preset transmission speed.

Step 208, determining the number of magnetic markers in the specific binding region of the target sample based on the magnetic field strength and the transmission displacement curve.

In this embodiment of the present application, the magnetic nanoparticles in the target sample can be combined with the antibody in a certain proportion, and after the antibody in the target sample is combined with the antigen of the solution to be tested, the antigen-antibody conjugate carrying the magnetic nanoparticles can be used as a magnetic marker and exhibit a magnetic field.

The data processing device determines the number of the magnetic markers in the specific binding area of the target sample according to the magnetic field intensity of the target sample in the magnetic field intensity and transmission displacement curve and the magnetic marker calculation parameters.

In the sample detection method, a target sample is driven towards the direction of the magnetic field measuring device by controlling the linear driving device; acquiring the magnetic field intensity of the target sample at each moment measured by the magnetic field measuring device in the transmission process of the target sample; acquiring the transmission time length of a target sample through a linear transmission device; determining a magnetic field intensity and transmission displacement curve aiming at the target sample according to the magnetic field intensity and transmission time length of the target sample at each moment; the number of magnetic markers in the specific binding region of the target sample is determined based on the magnetic field strength versus transmission displacement curve. By adopting the method, the relation curve between the specific binding position of the antigen antibody of the target sample and the magnetic field intensity can be determined based on the magnetic field intensity of the target sample at each moment and the transmission time of the target sample, and then the number of the magnetic markers in the specific binding region of the target sample can be quantitatively detected according to the relation curve between the specific binding position of the antigen antibody and the magnetic field intensity. Because the conversion of electromagnetic signals for multiple times is not needed, errors caused in the quantitative calculation process of the magnetic markers due to the fact that the electromagnetic signals are converted for multiple times by a complex algorithm can be avoided, and therefore accuracy of quantitative calculation of the magnetic markers in a target sample is improved.

In an exemplary embodiment, as shown in fig. 4, the magnetic field measuring apparatus includes an atomic magnetometer and a magnetic shielding cylinder for shielding magnetic field influence of geomagnetism on the atomic magnetometer, the atomic magnetometer is disposed in the magnetic shielding cylinder, for acquiring magnetic field intensity generated by a target sample in real time, and transmitting the magnetic field intensity generated by the target sample at each time to the data processing apparatus, and step 202 includes:

and controlling the linear transmission device to transmit the target sample to the direction of the magnetic shielding barrel and transmitting the target sample into the magnetic shielding barrel so that the target sample passes through the atomic magnetometer in the magnetic shielding barrel.

The atomic magnetometer may adopt a SERF (spin-exchange relaxation free ) atomic magnetometer, the working principle of the SERF atomic magnetometer is shown in fig. 5, the schematic structure diagram of the SERF atomic magnetometer is shown in fig. 6, and after a beam of circularly polarized pumping light is irradiated into the alkali metal atomic gas chamber, the alkali metal atom transitions from a ground state to an excited state, and the alkali metal atom generates spin polarization. Under the action of an external weak magnetic field, larmor precession can occur to an alkali metal atom, another beam of linearly polarized detection light is perpendicular to pumping light and enters the alkali metal air chamber, the Larmor precession is used for detecting atomic spin, and the relation between the external magnetic field strength and Larmor precession frequency can be shown by referring to a formula (I), and the specific content is as follows:

Omega = γiib iiformula (one)

Wherein ω characterizes larmor precession frequency; b represents the external magnetic field intensity; II B II represents the norm of B; gamma characterizes the magnetic spin ratio of the base atoms. The atomic magnetometer can indirectly obtain the magnitude of the magnetic field by measuring the larmor precession frequency of spin polarized atoms in the magnetic field, thereby achieving the purpose of magnetic field measurement.

Core unit as magnetic field detectionSpin-exchange relaxation-free (SERF) optically pumped atomic magnetometer (Quspin Inc.), comprising one ⁸⁷ An Rb steam pool is arranged on the bottom of the steam pool, the size is 3X 3mm ³ Electrically heated to about 150 c and defines an induction volume. By passing circularly polarized light beam ⁸⁷ Rb atomic gas cell, generates electron spin polarization. Because the working state of the SERF atomic magnetometer is close to zero magnetic field, a five-layer magnetic shielding is designed outside the atomic magnetometer, and the area with zero magnetic field condition is isolated from the environment magnetic field (such as geomagnetism). Typical external field attenuation is 10 ⁵ And 10 ⁶ The residual field can be further reduced by using a set of field coils mounted inside the shield.

Since the requisite for actuation of a SERF atomic magnetometer is the need to be in a near zero magnetic environment, a near zero magnetic operating environment needs to be provided for the SERF atomic magnetometer. The magnetic shielding cylinder is used for shielding the influence of geomagnetism on the starting of the SERF atomic magnetometer, the inner layer of the magnetic shielding cylinder is made of epoxy resin, the outer layer of the magnetic shielding cylinder is made of aluminum material, and the middle of the magnetic shielding cylinder is made of 5 layers of high-permeability permalloy (containing coils), and the structural design can enable the magnetic field value in the cylinder to be close to zero magnetism (the residual magnetism Br at the center point is less than or equal to 2 nT), so that the SERF atomic magnetometer can be ensured to normally start to work.

The linear transmission device is used for linearly transmitting the target sample into the magnetic shielding cylinder at a constant speed at a preset transmission speed, so that the target sample passes through the detection range of the atomic magnetometer probe. Specifically, the linear actuator is driven horizontally by a stepper motor in the mechanical actuator and scans along an axis perpendicular to the atomic magnetometer detection axis. In addition, the linear transmission device can also adjust the vertical distance (namely the distance in the z direction) between the sample to be measured and the atomic magnetometer probe so as to adjust the intensity of the residual magnetic flux density. The data processing device is used for collecting the value of the residual magnetization intensity detected by the atomic magnetometer when the target sample passes through the detection range of the atomic magnetometer probe, and recording the value of the residual magnetization intensity detected by the atomic magnetometer in real time.

In this embodiment of the application, the data processing device generates the control command according to the preset transmission speed, sends the control command to the linear transmission device to control the linear transmission device and transmit the target sample to the direction of the magnetic shielding barrel at the preset transmission speed, and transmit the target sample to the magnetic shielding barrel, so that the target sample passes through the atomic magnetometer in the magnetic shielding barrel.

In this example, the detection limit of the atomic magnetometer was 0.01ng mL ^-1 The method is enhanced by 100 times compared with an optical detection method, and the mechanism is more direct compared with other magnetic detection methods. Therefore, by combining the current measurement immunochromatography with the atomic magnetometer and providing an environment with near zero magnetism for the atomic magnetometer through the magnetic shielding barrel, the magnetic field intensity of a specific binding region in a target sample can be measured more accurately. Valuable insights are provided for potential application of atomic magnetometer quantum measurement technology in intelligent diagnosis and treatment, a quantifiable sensing mechanism scheme is provided for early and accurate screening of diseases, and development of life science metering fronts is expanded.

In an exemplary embodiment, as shown in FIG. 7, step 208 includes steps 702 and 704. Wherein:

step 702, determining a relationship between the specific binding position of the target sample and the magnetic field intensity based on the magnetic field intensity and the transmission displacement curve.

In the embodiment of the application, the data processing device determines the transmission displacement corresponding to the maximum value of the magnetic field intensity according to the magnetic field intensity and transmission displacement curve, and draws a relation curve of the specific binding position of the target sample and the magnetic field intensity according to the transmission displacement corresponding to the maximum value of the magnetic field intensity and transmission displacement curve.

Wherein the relationship between the specific binding site of the target sample and the magnetic field strength can be shown in FIG. 8

Step 704, determining the number of magnetic markers in the specific binding region of the target sample based on the relationship between the specific binding position of the target sample and the magnetic field strength.

In the embodiment of the application, the data processing device determines the number of the magnetic markers in the specific binding area of the target sample according to the magnetic field intensity of the target sample in the magnetic field intensity and transmission displacement curve and the magnetic marker calculation parameters.

In this embodiment, the number of the magnetic markers in the specific binding region of the target sample can be determined through the magnetic field strength and the transmission displacement curve, so as to realize quantitative detection of the magnetic markers in the specific binding region of the target sample. Because the magnetic nano-particles can be combined with the antibody in a certain proportion, the antigen can be combined with the antibody specifically, and therefore, the quantitative detection of the amount of the antigen in the target sample can be realized based on the amount of the magnetic marker in the target sample and the combination proportion of the magnetic nano-particles and the antibody.

In an exemplary embodiment, as shown in FIG. 9, step 206 includes steps 902 and 904. Wherein:

Step 902, determining the horizontal transmission displacement of the target sample according to the preset motion speed and the transmission duration of the target sample.

In the embodiment of the application, the data processing device can determine the horizontal transmission displacement of the target sample according to the preset motion speed and the transmission duration of the target sample. Specifically, the data processing device multiplies the preset motion speed and the transmission time length of the target sample to obtain the product of the preset motion speed and the transmission time length, and the product is used as the horizontal transmission displacement of the target sample.

Step 904, determining a magnetic field strength and transmission displacement curve for the target sample according to the magnetic field strength and horizontal transmission displacement of the target sample at each moment.

In the embodiment of the application, the data processing device displays the relationship between the magnetic field intensity and the transmission displacement of the target sample in real time through the LabVIEW through the magnetic field intensity of the target sample acquired by the atomic magnetometer in real time at each moment and the horizontal transmission displacement of the target sample at each moment, so as to obtain a magnetic field intensity and transmission displacement curve aiming at the target sample.

In this embodiment, the data processing device can determine the magnetic field intensity and the transmission displacement curve of the target sample through the magnetic field intensity of the target sample acquired by the atomic magnetometer in real time at each moment and the horizontal transmission displacement of the target sample at each moment, so that the subsequent data processing device can determine the number of the magnetic markers in the specific binding region of the target sample according to the magnetic field intensity and the transmission displacement curve of the target sample.

In an exemplary embodiment, as shown in FIG. 10, step 702 includes steps 1002 and 1004. Wherein:

in step 1002, the transmission displacement corresponding to the maximum value of the magnetic field strength in the curve of the magnetic field strength and the transmission displacement is set as the displacement zero point.

In this embodiment of the present application, the data processing device sets the transmission displacement corresponding to the maximum value of the magnetic field strength in the magnetic field strength and transmission displacement curve as the displacement zero point.

Step 1004, determining a relation curve of the specific binding position of the target sample and the magnetic field intensity according to the transmission displacement corresponding to the displacement zero point and the magnetic field intensity and transmission displacement curve.

In this embodiment, after the data processing device sets the transmission displacement corresponding to the maximum value of the magnetic field strength as the displacement zero point, the data processing device updates the transmission displacement corresponding to the transmission displacement smaller than the maximum value of the magnetic field strength in the magnetic field strength and transmission displacement curve into the displacement negative value, and updates the transmission displacement corresponding to the transmission displacement smaller than the maximum value of the magnetic field strength in the magnetic field strength and transmission displacement curve into the displacement positive value, so as to obtain the updated result corresponding to the magnetic field strength and transmission displacement curve.

And then, the data processing device redraws and obtains a relation curve of the specific binding position and the magnetic field intensity of the target sample according to each transmission displacement in the updating result corresponding to the magnetic field intensity and the transmission displacement curve and the magnetic field intensity corresponding to each transmission displacement in the transmission displacement curve.

In this embodiment, the data processing device can set the transmission displacement corresponding to the magnetic field intensity and the transmission displacement curve and the maximum magnetic field intensity as the displacement zero point, so as to obtain the relationship curve of the specific binding position of the target sample and the magnetic field intensity, and the subsequent data processing device can determine the number of the magnetic markers in the specific binding region of the target sample according to the relationship curve of the specific binding position of the target sample and the magnetic field intensity.

In an exemplary embodiment, as shown in FIG. 11, step 704 includes steps 1102 and 1104. Wherein:

step 1102, determining a target magnetization of a specific binding region of the target sample based on a relationship between the specific binding position of the target sample and the magnetic field strength, and the magnetic field calculation parameter.

In the embodiment of the application, the data processing device determines the relationship between the horizontal transmission displacement corresponding to the specific binding position of the target sample and the magnetic field intensity according to the relationship curve between the specific binding position of the target sample and the magnetic field intensity.

Then, the data processing device determines the target magnetization intensity of the specific binding region of the target sample according to the relationship between the horizontal transmission displacement corresponding to the specific binding position of the target sample and the magnetic field intensity and the magnetic field calculation parameter.

Step 1104, determining the number of magnetic markers in the specific binding region of the target sample based on the target magnetization and the magnetic marker calculation parameters in the specific binding region of the target sample.

In the embodiment of the application, the data processing device calculates and obtains the number of the magnetic markers in the specific binding region of the target sample according to the target magnetization intensity of the specific binding position in the target sample and the magnetic marker calculation parameters in the specific binding region of the target sample.

Wherein, because in the target sample, the magnetic nano particles can be combined with the antibody in a certain proportion, after the solution to be detected containing the antigen is dripped into the test strip corresponding to the target sample, the antigen in the solution to be detected can be combined with the antibody in the target sample in the specific combination area of the target sample. Antibodies in the target sample that do not bind to the antigen will move out of the specific binding region with the solution, and therefore, antibodies that do not bind to the antigen will carry the magnetic nanoparticles out of the specific binding region. The higher the concentration of the antigen in the solution to be detected, the more the antibody and the antigen are combined in the specific combination area of the target sample, namely the more the number of the magnetic nano particles is, the larger the magnetic field intensity of the target sample is.

In this embodiment, the data processing device can calculate and obtain the number of the magnetic markers in the specific binding region of the target sample, thereby realizing quantitative detection of the magnetic nanoparticles in the specific binding region of the target sample.

In an exemplary embodiment, the magnetic field calculation parameters include background magnetic field, vacuum permeability, and vertical distance of the atomic magnetometer from the target sample, step 1102 comprises:

and fitting the relation curve of the specific binding position of the target sample and the magnetic field intensity based on the relation curve of the specific binding position of the target sample and the magnetic field intensity, the vacuum magnetic permeability, the vertical distance between the atomic magnetometer and the target sample, the transmission displacement corresponding to the maximum value of the magnetic field intensity and the horizontal transmission displacement of the target sample, and determining the target magnetization of the specific binding region of the target sample.

The magnetic shielding cylinder can shield a magnetic field outside the magnetic shielding cylinder, such as geomagnetism, so that the value of the background magnetic field in the magnetic shielding cylinder is 0; the vacuum permeability can be 4 pi multiplied by 10 ^-7 T m A ^-1 。

In the embodiment of the application, the data processing device can control the linear transmission device to transmit the target sample in the vertical direction through the control instruction, and acquire the displacement of the linear transmission device to transmit the target sample in the vertical direction.

The data processing device is capable of controlling the linear actuator to move in a vertical direction by means of control instructions, so that the target sample fixed to the linear actuator can be located in the same plane as the atomic magnetometer, thereby enabling the atomic magnetometer to obtain a more accurate magnetic field strength of the target sample.

The data processing means can then determine the true value of the vertical distance of the atomic magnetometer from the target sample based on the original position of the target sample, the displacement of the target sample in the vertical direction, and the position of the atomic magnetometer.

The data processing device is based on a relation curve of the specific binding position of the target sample and the magnetic field intensity, a true value of the vertical distance between the vacuum magnetic permeability and the target sample, a transmission displacement corresponding to the maximum value of the magnetic field intensity and a horizontal transmission displacement of the target sample, and the data processing device can use a least square method to fit the relation curve of the specific binding position of the target sample and the magnetic field intensity, so as to determine the target magnetization intensity of the specific binding region of the target sample. For the process of fitting a curve of the relationship between the specific binding position of the target sample and the magnetic field strength to determine the target magnetization of the specific binding region of the target sample, reference may be made to formula (two), which is specifically described as follows:

Wherein B characterizes the magnetic field strength (i.e., the remanent flux density Br of the target sample); b (B) ₀ Characterizing a background magnetic field; mu (mu) ₀ Characterizing vacuum permeability; x represents the horizontal transmission displacement of the target sample; x is x ₀ Representing the horizontal transmission displacement of a target sample corresponding to the maximum value of the magnetic field intensity; d represents a calculated value of the vertical distance between the atomic magnetometer and the target sample; m characterizes the target magnetization.

The data processing device fits according to the horizontal transmission displacement x and the magnetic field intensity B of the target sample in the relation curve of the specific binding position and the magnetic field intensity of the target sample and the formula (II), so that the calculated value d of the magnetization M of the magnetic nano particles in the specific binding region in the target sample and the vertical distance between the atomic magnetometer and the target sample can be obtained.

Wherein the true value of the perpendicular distance of the atomic magnetometer from the target sample is used to determine the accuracy of the magnetization M, in particular the true value d of the perpendicular distance of the atomic magnetometer from the target sample _z (i.e., d in FIG. 3) _z ) And under the condition that the difference value between the calculated value of the vertical distance between the atomic magnetometer and the target sample is smaller than a preset threshold value, the data processing device can determine that the calculation accuracy of the magnetic field intensity B is higher.

In this embodiment, the data processing apparatus can determine the target magnetization of the specific binding region of the target sample by using a relationship curve between the specific binding position and the magnetic field intensity of the target sample, the vacuum permeability, the vertical distance between the atomic magnetometer and the target sample, the transmission displacement corresponding to the maximum value of the magnetic field intensity, and the horizontal transmission displacement of the target sample. The subsequent data processing device is convenient to determine the number of the magnetic nano particles in the specific binding area of the target sample according to the target magnetization intensity.

In an exemplary embodiment, the magnetic marker calculation parameters include the density of magnetic nanoparticles in the target sample, the volume of magnetic nanoparticles, and the saturation magnetization of magnetic nanoparticles, as shown in fig. 12, step 1204 includes steps 1202 and 1204. Wherein:

step 1202, determining a magnetization parameter based on a density of magnetic nanoparticles in a target sample, a volume of the magnetic nanoparticles, and a saturation magnetization of the magnetic nanoparticles.

Wherein the magnetization parameter is positively correlated with the density of the magnetic nanoparticles in the target sample, the volume of the magnetic nanoparticles, and the saturation magnetization of the magnetic nanoparticles.

In this embodiment of the present application, the data processing device may determine the magnetization parameter based on the density of the magnetic nanoparticles in the target sample, the volume of the magnetic nanoparticles, and the saturation magnetization of the magnetic nanoparticles, and for the method for determining the magnetization parameter, reference may be made to formula (iii), where the specific contents are as follows:

n1＝M _S ρ, V formula (III)

Wherein n1 characterizes a magnetization parameter; m is M _s Characterization of the saturation magnetization of the individual magnetic nanoparticles, M _s Can be measured by a Vibrating Sample Magnetometer (VSM); ρ characterizes the density of individual magnetic nanoparticles; v characterizes the volume of individual magnetic nanoparticles. The method for determining the saturation magnetization, density, and volume of individual magnetic nanoparticles in a target sample is not particularly limited in the examples herein.

Step 1204, determining the number of magnetic markers in the specific binding region of the target sample based on the magnetization parameter and the target magnetization.

Wherein the number of magnetic markers is inversely related to the magnetization parameter and the number of magnetic markers is positively related to the target magnetization.

In the embodiment of the application, the data processing device determines the number of the magnetic markers in the specific binding region of the target sample according to the magnetization parameter and the target magnetization intensity. For a method of determining the amount of the magnetic marker in the specific binding region of the target sample, reference may be made to formula (four), which is specifically described as follows:

Wherein n characterizes the number of magnetic markers in the specific binding region of the target sample; m represents the target magnetization; n1 characterizes the magnetization parameter.

In this embodiment, the data processing device can obtain the magnetic nanoparticle data in the specific binding region of the target sample based on the target magnetization and the magnetization parameter, and can realize quantitative detection of the magnetic nanoparticles.

In one embodiment, a processing procedure example of the sample detection method is also provided, and the specific contents are as follows:

step S1, taking a certain volume of solution containing the magnetic markers (namely magnetic nano particles) to be detected, and obtaining the relationship between the volume of the solution and the number of the magnetic markers through a liquid particle counter.

Step S2, part of the solution in the solution containing the magnetic marker to be detected is dripped on the test paper (the size of the test paper area is 1 multiplied by 3 multiplied by 0.15mm of the specific binding area) ³ ) Obtaining a target sample, measuring the magnetic field intensity of a specific binding region in the target sample by the sample detection method in the previous embodiment, and calculating the value of the target magnetization by the formula (II).

And S3, constructing a relation between the magnetic marker quantity and the target magnetization according to the relation between the solution volume and the magnetic marker quantity and the target magnetization value.

And S4, testing the target sample, and obtaining the number of the magnetic markers of the sample to be tested according to the value of the target magnetization intensity of the target sample, the formula (III) and the formula (IV).

In one embodiment, a detection process example of the sample detection method is also provided, and the specific content includes:

in the embodiment of the application, taking the quantitative detection of carcinoembryonic antigen (CEA) immunochromatographic test paper as an example, the feasibility of the quantitative method is proved. The technical staff prepares the solution containing the carcinoembryonic antigen with the same concentration and the magnetic marker and uses the biosensing platform based on the atomic magnetometer to detect after the immunochromatography, and the detection result of the immunochromatography test paper containing the carcinoembryonic antigen with different concentrations is shown in figure 13.

The CEA pure solution was diluted to 0 (no CEA) and 0.001ng mL in physiological saline, respectively ^-1 、0.01ng mL ^-1 、0.1ng mL ^-1 、1ng mL ^-1 、10ng mL ^-1 And 50ng mL ^-1 And detected by the prepared MNP (magnetic nanoparticle) -based LFIA test strip for 15min to obtain a result, as shown in FIG. 6, with CEA concentration of 0ng mL ^-1 Increase to 50ng mL ^-1 The color intensity on the T line (Test line) deepens. Meanwhile, AMB (a device for acquiring the tangential component spectrum of the residual magnetic flux density) is adopted to continuously and linearly scan the LFIA test strips with different CEA concentrations, and the tangential component spectrum of the residual magnetic flux density is respectively recorded.

Referring to FIG. 13, a tangential component distribution pattern of residual magnetic flux density on the T line and C line (Control line) of the chromatographic test strip obtained by AMB can be obtained when CEA concentration is as low as 0.001ng mL ^-1 And 0ng mL ^-1 When the residual magnetic flux density on the T-line is still measured, and the magnetic field strength increases with increasing CEA concentration. 0 and 0.001ng mL ^-1 The reason why the magnetic signal of the T-line of the sample is weak can be ascribed to a small amount of magnetic nanoparticles deposited on the NC film (nitrocellulose filter membrane, nitrocellulose film).The CEA concentration target versus magnetization M value obtained from the magnetic flux density distribution curve is shown in FIG. 14, except that the concentration is 0.001ng mL ^-1 In addition to the samples of (a), the target magnetization M value of all samples increases with increasing CEA concentration C, 0ng mL ^-1 The target magnetization of the sample had a value of 1.87×10 ^-10 A m ² Slightly less than 0.001ng mL ^-1 And (3) a sample. Based on the relation between the target magnetization M and the magnetic nanoparticle N, the CEA concentration on the T line is estimated to be 0, 0.001ng mL ^-1 、0.01ng mL ^-1 、0.1ng mL ^-1 、1ng mL ^-1 、10ng mL ^-1 And 50ng mL ^-1 The number of magnetic nanoparticles was 3.162×10, respectively ³ 、1.645×10 ⁴ 、3.672×10 ³ 、2.537×10 ⁴ 、3.006×10 ⁴ 、6.331×10 ⁴ And 2.042 ×10 ⁶ 。

In order to more intuitively understand the effect of CEA concentration variation on the tangential component map of residual magnetic flux density, the magnetic field strength ratio between T line and C line is calculated to establish the signal strength between CEA concentrations, because the ratio of T line and C line can effectively counteract the effects of inherent heterogeneity and matrix effect of the test paper. As shown in FIG. 15, the relationship between the magnetic field strength ratio (MIt/c) and the logarithm of the concentration is 0.01ng mL ^-1 To 50ng mL ^-1 With a good linear range (linear relationship y=0.102x+0.462), R ² 0.9571. Since there is a small amount of MNP residue in NC membrane, 0ng mL ^-1 The MIt/c of the sample was 0.2680, slightly below 0.01ng mL ^-1 And (3) a sample.

Compared with other detection methods, the sample detection method provided by the application can provide absolute quantitative results of magnetic nano particles, and the detection sensitivity is higher.

TABLE 1 characterization of immunochromatographic test paper sensors for different detection mechanisms

It should be understood that, although the steps in the flowcharts related to the embodiments described above are sequentially shown as indicated by arrows, these steps are not necessarily sequentially performed in the order indicated by the arrows. The steps are not strictly limited to the order of execution unless explicitly recited herein, and the steps may be executed in other orders. Moreover, at least some of the steps in the flowcharts described in the above embodiments may include a plurality of steps or a plurality of stages, which are not necessarily performed at the same time, but may be performed at different times, and the order of the steps or stages is not necessarily performed sequentially, but may be performed alternately or alternately with at least some of the other steps or stages.

Based on the same inventive concept, the embodiment of the application also provides a sample detection device for realizing the above-mentioned sample detection method. The implementation of the solution provided by the device is similar to that described in the above method, so the specific limitations of one or more embodiments of the sample detection device provided below can be referred to above for the limitations of the sample detection method, and are not repeated here.

In one exemplary embodiment, as shown in fig. 16, there is provided a sample detection device 1600 comprising: a control module 1602, an acquisition module 1604, a first determination module 1606, and a second determination module 1608, wherein:

and the control module 1602 is used for controlling the linear transmission device to transmit the target sample to the direction of the magnetic field measuring device.

The obtaining module 1604 is configured to obtain, during a transmission process of the target sample, a magnetic field strength of the target sample at each moment measured by the magnetic field measurement device, and a transmission time period of the target sample.

A first determining module 1606 is configured to determine a magnetic field strength versus transmission displacement curve for the target sample according to the magnetic field strength of the target sample at each moment and the transmission duration.

A second determination module 1608 for determining the number of magnetic markers in the specific binding region of the target sample based on the magnetic field strength versus transmission displacement curve.

By adopting the sample detection device provided by the embodiment of the application, the relation curve between the specific binding position of the antigen-antibody of the target sample and the magnetic field intensity can be determined based on the magnetic field intensity of the target sample at each moment and the transmission time of the target sample, and then the number of the magnetic markers in the specific binding region of the target sample can be quantitatively detected according to the relation curve between the specific binding position of the antigen-antibody and the magnetic field intensity. Because the conversion of electromagnetic signals for multiple times is not needed, errors caused in the quantitative calculation process of the magnetic markers due to the fact that the electromagnetic signals are converted for multiple times by a complex algorithm can be avoided, and therefore accuracy of quantitative calculation of the magnetic markers in a target sample is improved.

In one embodiment, the control module 1602 is specifically configured to:

In one embodiment, the second determining module 1608 is specifically configured to:

In one embodiment, the first determining module 1606 is specifically configured to:

In one embodiment, the magnetic field calculation parameters include a background magnetic field, a vacuum permeability, and a vertical distance of the atomic magnetometer from the target sample, and the second determination module 1608 is specifically configured to:

In one embodiment, the magnetic marker calculation parameters include a density of magnetic nanoparticles in the target sample, a volume of the magnetic nanoparticles, and a saturation magnetization of the magnetic nanoparticles, and the second determination module 1608 is specifically configured to:

The various modules in the sample detection device described above may be implemented in whole or in part by software, hardware, and combinations thereof. The above modules may be embedded in hardware or may be independent of a processor in the computer device, or may be stored in software in a memory in the computer device, so that the processor may call and execute operations corresponding to the above modules.

In an exemplary embodiment, a computer device, which may be a terminal, is provided, and an internal structure thereof may be as shown in fig. 17. The computer device includes a processor, a memory, an input/output interface, a communication interface, a display unit, and an input means. The processor, the memory and the input/output interface are connected through a system bus, and the communication interface, the display unit and the input device are connected to the system bus through the input/output interface. Wherein the processor of the computer device is configured to provide computing and control capabilities. The memory of the computer device includes a non-volatile storage medium and an internal memory. The non-volatile storage medium stores an operating system and a computer program. The internal memory provides an environment for the operation of the operating system and computer programs in the non-volatile storage media. The input/output interface of the computer device is used to exchange information between the processor and the external device. The communication interface of the computer device is used for carrying out wired or wireless communication with an external terminal, and the wireless mode can be realized through WIFI, a mobile cellular network, NFC (near field communication) or other technologies. The computer program is executed by a processor to implement a sample detection method. The display unit of the computer device is used for forming a visual picture, and can be a display screen, a projection device or a virtual reality imaging device. The display screen can be a liquid crystal display screen or an electronic ink display screen, and the input device of the computer equipment can be a touch layer covered on the display screen, can also be a key, a track ball or a touch pad arranged on the shell of the computer equipment, and can also be an external keyboard, a touch pad or a mouse and the like.

It will be appreciated by those skilled in the art that the structure shown in fig. 17 is merely a block diagram of a portion of the structure associated with the present application and is not limiting of the computer device to which the present application applies, and that a particular computer device may include more or fewer components than shown, or may combine certain components, or have a different arrangement of components.

In an exemplary embodiment, a computer device is provided, comprising a memory and a processor, the memory having stored therein a computer program, the processor performing the steps of the method embodiments described above when the computer program is executed.

In one embodiment, a computer-readable storage medium is provided, on which a computer program is stored which, when executed by a processor, implements the steps of the method embodiments described above.

In an embodiment, a computer program product is provided, comprising a computer program which, when executed by a processor, implements the steps of the method embodiments described above.

It should be noted that, the user information (including, but not limited to, user equipment information, user personal information, etc.) and the data (including, but not limited to, data for analysis, stored data, presented data, etc.) referred to in the present application are information and data authorized by the user or sufficiently authorized by each party, and the collection, use, and processing of the related data are required to meet the related regulations.

Those skilled in the art will appreciate that implementing all or part of the above described methods may be accomplished by way of a computer program stored on a non-transitory computer readable storage medium, which when executed, may comprise the steps of the embodiments of the methods described above. Any reference to memory, database, or other medium used in the various embodiments provided herein may include at least one of non-volatile and volatile memory. The nonvolatile Memory may include Read-Only Memory (ROM), magnetic tape, floppy disk, flash Memory, optical Memory, high density embedded nonvolatile Memory, resistive random access Memory (ReRAM), magnetic random access Memory (Magnetoresistive Random Access Memory, MRAM), ferroelectric Memory (Ferroelectric Random Access Memory, FRAM), phase change Memory (Phase Change Memory, PCM), graphene Memory, and the like. Volatile memory can include random access memory (Random Access Memory, RAM) or external cache memory, and the like. By way of illustration, and not limitation, RAM can be in the form of a variety of forms, such as static random access memory (Static Random Access Memory, SRAM) or dynamic random access memory (Dynamic Random Access Memory, DRAM), and the like. The databases referred to in the various embodiments provided herein may include at least one of relational databases and non-relational databases. The non-relational database may include, but is not limited to, a blockchain-based distributed database, and the like. The processors referred to in the embodiments provided herein may be general purpose processors, central processing units, graphics processors, digital signal processors, programmable logic units, quantum computing-based data processing logic units, etc., without being limited thereto.

The technical features of the above embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.

The above examples only represent a few embodiments of the present application, which are described in more detail and are not to be construed as limiting the scope of the present application. It should be noted that it would be apparent to those skilled in the art that various modifications and improvements could be made without departing from the spirit of the present application, which would be within the scope of the present application. Accordingly, the scope of protection of the present application shall be subject to the appended claims.

Claims

1. A method of sample detection, characterized by a data processing device for use in a sample detection system, the sample detection system further comprising a magnetic field measurement device and a linear actuator, the method comprising:

2. The method of claim 1, wherein the magnetic field measuring device comprises an atomic magnetometer and a magnetic shielding cylinder, the magnetic shielding cylinder is used for shielding magnetic field influence of geomagnetism on the atomic magnetometer, the atomic magnetometer is arranged in the magnetic shielding cylinder and used for acquiring magnetic field intensity generated by the target sample in real time and transmitting the magnetic field intensity generated by the target sample at each moment to the data processing device, and the controlling the linear transmission device transmits the target sample to the direction of the magnetic field measuring device comprises:

3. The method of claim 1 or 2, wherein the determining the amount of magnetic marker in the specific binding region of the target sample based on the magnetic field strength versus transmission displacement curve comprises:

4. The method of claim 1, wherein determining a magnetic field strength versus drive displacement curve for the target sample based on the magnetic field strength of the target sample at each time and the drive time period comprises:

5. The method of claim 3, wherein determining the specific binding position versus magnetic field strength for the target sample based on the magnetic field strength versus transmission displacement curve comprises:

6. The method of claim 3, wherein the determining the amount of the magnetic marker in the specific binding region of the target sample based on the specific binding position of the target sample versus the magnetic field strength comprises:

7. The method of claim 6, wherein the magnetic field calculation parameters include a background magnetic field, a vacuum permeability, and a perpendicular distance of an atomic magnetometer from the target sample, wherein the determining the target magnetization of the specific binding region of the target sample based on the specific binding position of the target sample versus the magnetic field strength, and the magnetic field calculation parameters, comprises:

8. The method of claim 6, wherein the magnetic marker calculation parameters include a density of magnetic nanoparticles in the target sample, a volume of the magnetic nanoparticles, and a saturation magnetization of the magnetic nanoparticles, and wherein the determining the number of magnetic markers in the specific binding region of the target sample based on the target magnetization, the magnetic marker calculation parameters in the specific binding region of the target sample comprises:

9. A sample testing device, the device comprising:

10. A computer device comprising a memory and a processor, the memory storing a computer program, characterized in that the processor implements the steps of the method of any one of claims 1 to 8 when the computer program is executed.

11. A computer readable storage medium, on which a computer program is stored, characterized in that the computer program, when being executed by a processor, implements the steps of the method of any of claims 1 to 8.

12. A computer program product comprising a computer program, characterized in that the computer program, when executed by a processor, implements the steps of the method of any one of claims 1 to 8.