CN113219170A - Magnetic immunoassay system and method of use - Google Patents

Magnetic immunoassay system and method of use Download PDF

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CN113219170A
CN113219170A CN202110462114.8A CN202110462114A CN113219170A CN 113219170 A CN113219170 A CN 113219170A CN 202110462114 A CN202110462114 A CN 202110462114A CN 113219170 A CN113219170 A CN 113219170A
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resistor
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CN113219170B (en
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褚正康
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Chongqing Yunxin Medical Technology Co.,Ltd.
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Chengdu Yunxin Medical Technology Co Ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/558Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
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    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302Apparatus specially adapted for immunological test procedures
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/12Measuring magnetic properties of articles or specimens of solids or fluids
    • G01R33/1276Measuring magnetic properties of articles or specimens of solids or fluids of magnetic particles, e.g. imaging of magnetic nanoparticles

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Abstract

The invention provides a magnetic immunity detection system and a using method thereof, wherein the magnetic immunity detection system consists of four parts, namely a magnetic resistance sensor, an analog front end, a central processing unit and a digital signal processing unit. A magnetoresistive sensor comprises two magnetoresistive elements connected in series and a permanent magnet for uniformly applying a magnetic field to the two magnetoresistive elements, an output terminal is provided at the junction of the two magnetoresistive elements, and the voltage at the output terminal is referred to as the output voltage VoWhen the input voltage V isiWhen applied across the MR device, the output voltage is approximately half the input voltage, the voltage being the median voltage. The invention can reduce the interference of the sample as much as possible by utilizing the characteristics of magnetism, can realize the quantitative detection of the detected sample, can realize the miniaturization of equipment and further promote the development of POCT.

Description

Magnetic immunoassay system and method of use
Technical Field
The invention belongs to the technical field of detection, and particularly relates to a magnetic immunoassay system and a using method thereof.
Background
The Point-of-care testing (POCT) technology has the characteristics of rapid testing, simplicity in use, cost saving and the like, and with the emphasis on health care on accurate medical treatment, population health and chronic disease management, the potential influence of POCT appears on a remarkable strengthening trend in the past decade.
ICTSs (Immunochromatographic test strips) are POCT diagnosis formats with the greatest development prospect, have the characteristics of rapidness, simplicity, convenience, high cost benefit and the like, and are widely applied to POCT detection at present. Immunochromatography is an immunoassay method widely applied to field detection. Mainly adopts colloidal gold, fluorescent microspheres, magnetic nanoparticles and the like as markers, and realizes the detection of the content of SAA (Serum amyloid sample protein A, Serum amyloid A) protein and the like in Serum, plasma and whole blood samples in an immunochromatography mode in cooperation with an immunoassay analyzer. Colloidal gold is currently one of the most commonly used nanoparticles due to its physical stability and low cost. However, it can only perform semi-quantitative analysis based on visual observation, and has no specific data. The conventional immunofluorescence technique has a certain limitation in measuring the content of the antigen, because many complexes and proteins in biological fluid and serum can emit fluorescence, and when the biological sample is marked by a fluorescent substance, the fluorescence generated by the biological sample interferes the experiment, so that the sensitivity of the detection of the experiment is seriously reduced. Some of these methods are time consuming, some are large instruments, are only suitable for stationary applications, and require complicated operations, which limits their use in POCT.
A new class of label materials, superparamagnetic nanoparticles (SPMNPs), has also been developed in recent years. It can replace traditional labeling materials such as colloidal gold, latex, selenium, carbon and liposome to carry out quantitative detection. At present, no related quantitative detection product exists in the market. Magnetic nanoparticles are a magnetic material with a size of 1-100 nm. It has unique optical, magnetic, electric, thermal, mechanical and chemical activity and wide application foreground in magnetic nanometer particle based diagnosis technology. Compared with the traditional immunochromatographic test paper which utilizes color intensity to determine signal intensity, the immunochromatographic test paper based on superparamagnetic nano particles can determine the signal intensity through magnetic analysis reading, and compared with the immunochromatographic test paper, the immunochromatographic test paper based on superparamagnetic nano particles can read magnetic signals through a Magnetic Analysis Reader (MAR) system to realize quantitative measurement. General biological samples, such as saliva, blood, etc., do not contain substances causing paramagnetic noise, and thus, compared to a reader using an optical sensor, a quantitative reader using a magnetic field sensor has almost no background noise and has better specificity in detecting biological samples. The magnetic signals provided by the SPMNPs are quite stable, and the detection results can be rechecked.
With the advance of sensor technology, more and more quantitative detection methods based on magnetoplague are reported, and some other studies in the literature are listed below.
(1) Magnetic Assay Reader (MAR)
The MAR analysis system (MAR) developed and sold by Magna biosciences LLC (CA, USA) is widely used for quantitative analysis of magnetic nanoparticle labeled samples. HCG, listeria monocytogenes, bacillus anthracis, and Human Immunodeficiency Virus (HIV) type p24 antigen. The MAR is formed by exciting MNPs with superparamagnetic property by an external magnetic field generated by a C-type electromagnet, and taking the other set of thin film induction coils as a unit for collecting and measuring magnetic signals. The measured magnetic signal intensity is in a linear relationship with the quantity of MNPs accumulated on the test strip within a certain range, and the magnetic signal intensity is recorded by using related magnetic units.
(2) Giant magnetoresistance sense reader (GMR)
Magnetic saturation refers to a ferromagnetic substance or a ferrimagnetic substance in a state where the magnetic polarization strength does not increase significantly with an increase in magnetic field strength. In addition to MAR, MIR readers, parameters of the target protein are quantitatively analyzed by measuring the saturation of magnetization produced by MNPs using a magnetic sensor. In lateral flow immunoassays, GMR is widely used in the quantitative analysis of MNPs labeled target proteins, Ryu et al. The cardiac marker cTNl was detected using a GMR sensor with a sensitivity of 0.01 ng/ml.
(3) Tunnel Magnetoresistive Reader (TMR)
Tunneling Magnetoresistive (TMR) sensing. Lei et al, have developed a non-contact sensor system for quantitatively detecting MNPs accumulated on LFTSs. A direct current is applied to the C-shaped electromagnet to generate a vertical magnetic field, two TMR elements which are adjacent in parallel are added in a gap area of the C-shaped electromagnet, and the differential structure is sensitive to the change of a stray magnetic field caused by MNPs in the direction of the test strip. In the detection device, the test strip is moved in the horizontal direction by the sliding guide rail, and then the TMR sensor converts the change of the magnetic signal into voltage information. Finally, the device achieves the detection limit of 25mlU/mL by combining the detection of HCG, and fully shows that the TMR sensor can still achieve a good sensitivity and accuracy requirement in a non-contact sensor mode.
Disadvantages of the first prior art
In the above described devices, the MAR cannot automatically locate the position requiring manual correction. The GMR detection wheel may damage the structure of the test strip, which brings errors to the result. TMR sensors are bulky, which all restrict POCT development of magnetoimmune-based protein detection systems.
Disclosure of Invention
The invention aims to solve the defects of the prior art, the position of the test paper can be automatically detected and adjusted by a positioning detection algorithm, the lnSb single crystal is used as a magnetoresistive sensor of a magnetoresistive element, the volume of a mechanical mechanism of the whole system can be only 98mm multiplied by 62mm multiplied by 78mm, the non-contact detection with the paper to be tested can be realized, and the structure of the test paper strip cannot be damaged.
The invention adopts the following technical scheme:
the magnetic immunity detection system consists of four parts, namely a magnetic resistance sensor, an analog front end, a central processing unit and a digital signal processing unit.
The magneto-resistive sensor comprises two magneto-resistive devices (MR1, MR2) and a permanent magnet, wherein the two magneto-resistive devices are connected in series, the permanent magnet applies a uniform magnetic field to the two magneto-resistive devices, an output terminal I is arranged at the joint of the two magneto-resistive devices, and the output terminal I is connected with the analog front end;
the voltage at this terminal is called the output voltage VoWhen the input voltage V isiWhen applied across the magnetoresistive device, the output voltage is approximately half the input voltage, the voltage being the median voltage. However, if magnetic fields of different strengths act on the two magnetoresistive devices, the output and the median voltage may differ due to the difference in resistance values of the devices.
The analog front end is a second-order active band-pass filter, the second-order active band-pass filter adopts a two-stage operational amplifier circuit to process signals detected by the magnetic resistance sensor, and the processed signals are input into the central processing unit;
the central processing unit is collected and converted into digital signals by the ADC, stored in a FLASH of the central processing unit and communicated with the digital signal processing unit through a serial port;
a digital signal processing unit: and completing the display, analysis and processing of the signal waveform.
The magneto-resistive sensor further comprises a coupling circuit, wherein the coupling circuit comprises a power supply, a resistor R11 and a resistor R12, the output end of the resistor R11 is connected with the input end of the resistor R12 in series, an output terminal II is arranged at the connection position of the resistor R11 and the resistor R12 and connected with the analog front end, one end of the power supply is connected with the input end of the resistor R11, and the other end of the power supply is connected with the output end of the resistor R12.
The second-order active band-pass filter is an improved first-order capacitor filter, and is characterized in that a capacitor C1 is arranged between a resistor R1 and an input Vin, an input Vi is introduced into a '+' end of an amplifier, specifically, the '+' end is connected with one end of a resistor R3 and one end of a resistor R4, the other end of the resistor R4 is grounded, and a resistor R3 is connected with the input VI.
The further technical scheme is that the analog front end is provided with two second-order active band-pass filters, an output terminal I of a magnetoresistive sensor is connected with a minus input side of a 1# second-order active band-pass filter and is particularly connected with one end of a capacitor C1, an output of the 1# second-order active band-pass filter is connected with a minus input side of a 2# active band-pass filter and is particularly connected with one end of a capacitor C1, and an output terminal II of the magnetoresistive sensor is respectively connected with a plus input side of the 1# second-order active band-pass filter and a plus input side of the 2# second-order active band-pass filter and is particularly connected with a resistor R3 of the 1# second-order active band-pass filter and a resistor R7 of the 2# second-order active band-pass filter.
Further, magnetic resistance sensor installs on the magnetic resistance sensor support, magnetic resistance sensor support joint is on the shell, the paper that awaits measuring is installed in the recess at test cassette middle part, the test cassette is installed on the gear board, the gear board is installed on the slide rail, the slide rail is installed in the mounting groove at shell middle part, test cassette joint is on the both sides board of shell, step motor installs in base one side, the shell is installed on the base, step motor's gear and gear board meshing, the gear board slides on the slide rail, the direction of advance is injectd by the slide rail, the simulation front end, central processing unit all places in the base.
The use method of the magnetic immunoassay system comprises the following steps:
step 1, performing immunochromatography reaction on paper to be tested;
step 2, installing the paper to be tested in the groove in the middle of the test card holder, sending a corresponding instruction by the central processing unit, controlling the stepping motor to operate, driving the gear plate to move horizontally, scanning the whole paper to be tested by the magnetic resistance sensor fixed on the shell through the magnetic resistance sensor support, and transmitting the detected signal to the central processing unit for processing;
and 3, storing the signal waveform in a FLASH of the central processing unit, communicating with the digital signal processing unit through a serial port, and establishing a graphical user interface on the digital signal processing unit to display, analyze and process the signal waveform.
The invention has the beneficial effects that:
the invention researches and designs a system for detecting a detection sample based on SPMNPs (SpInMP magnetic probes) by adopting a magnetoresistive sensor, wherein the system uses an STM32 singlechip as a main control chip, controls a stepping motor to drive a test paper base to move, scans weak magnetic signals on test paper by the magnetoresistive sensor, filters and amplifies the weak magnetic signals by a differential amplification filter circuit, and the processed signals adopt a 12-bit high-precision ADC (analog to digital converter) to acquire data. The use of Python creates a simple graphical user interface that is convenient to use for rapid performance of repeat tests, display of detected waveforms, and analytical observation. The invention uses the detection samples with different concentrations to carry out a plurality of tests, and the result has good repeatability. The whole system has the advantages of small size, high detection speed, strong specificity, simplicity and convenience and the like, and has good application prospects in the aspects of POCT, environmental detection, food analysis and the like.
Drawings
FIG. 1(a) is a schematic structural diagram of an immuno-layer chromatography test paper of the present invention;
FIG. 1(b) is a schematic diagram showing a positive reaction of the immuno-layer assay test paper of the present invention;
FIG. 1(c) is a schematic view showing a negative reaction of the immuno-layer assay test paper of the present invention;
FIG. 2(a) is a view showing an internal structure of an InSb single crystal magnetoresistive sensor;
FIG. 2(b) is a schematic diagram of the detection of a magnetoresistive sensor;
FIG. 3(a) is a state diagram of a circuit when there is no magnetic substance to be detected;
FIG. 3(b) is a state diagram of a circuit when the magnetic substance to be detected moves to MR 2;
FIG. 3(c) is a state diagram of a circuit when the magnetic substance to be detected moves to MR 1;
FIG. 3(d) is a graph showing the output V of the magnetic substance to be detected during the entire movement0A schematic diagram;
FIG. 4(a) is a typical first order integration circuit diagram;
FIG. 4(b) is a circuit diagram of an improvement over a typical first order integration circuit diagram;
FIG. 5(a) is a block diagram showing the overall structure of the system;
FIG. 5(b) is a 3D schematic of the mechanical structure of the system;
fig. 5(c) is a schematic exploded view of the mechanical structure of the system.
In the figure, 101-a magnetoresistive sensor, 102-a stepping motor, 103-a test card seat, 104-a transmission mechanism, 105-to-be-tested paper, 106-a base, 107-a magnetoresistive sensor bracket, 108-a shell, 109-a gear plate and 1010-a slide rail;
an A-sample pad, a B-conjugate pad, a C-NC membrane, a D-detection line, an E-control line, an F-PVC plate, and a G-adsorption pad.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention are described below clearly and completely, and it is obvious that the described embodiments are some, not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
As shown in fig. 1(a) -1 (C), the immunochromatographic paper (ICTS) of the present invention is mainly composed of a sample pad a, a conjugate pad B, NC membrane C, a detection line D, a control line E, PVC plate F, and an adsorption pad G.
The general principle of immunochromatography is based on antibody-antigen specific interactions. SMNPs were initially labeled on antibodies (Ab) to form SMNPs-Ab conjugates, and can be immobilized on conjugate pad G.
The detection line (TL) on the immunochromatographic strip contains a target hapten capable of capturing the target antigen, and the specific immunoglobulin antibody (Ab1) is immobilized on the Control Line (CL). When a test sample containing an antigen is coated on the sample pad a, the sample flows to the adsorption pad G by capillary force. In this process, the antigen binds to the magnetic nanoparticle-labeled antibody to form a conjugate (Ag-MNPs-Ab). Due to competition limitations, the target hapten fails to capture the flowing Ag-SMNPs-Ab in the detection line d (tl), while the Ag-SMNPs-Ab continues to the control line e (cl) and is captured by Ab1 in the control line e (cl). Finally, the remaining test sample reaches the absorbent pad G at the end of the test strip. The test results are shown in detection line d (tl) and control line e (cl) on NC film C.
Thus, as the Ab concentration increases, the signal on detection line d (tl) decreases. Based on this property, the properties of the sample can be quantitatively analyzed by detecting the magnetic field strength in the detection line d (tl) and the control line e (cl).
When a test sample containing an antigen is coated on the sample pad as shown in fig. 1(b), the sample flows toward the adsorption pad G by capillary force. In this process, the antigen binds to the magnetic nanoparticle-labeled antibody to form a conjugate (Ag-MNPs-Ab). Due to competition limitations, the target hapten fails to capture the flowing Ag-SMNPs-Ab in the detection line (TL), while the Ag-SMNPs-Ab continues to the control line e (cl) and is captured by Ab1 in the control line e (cl). The instrument can now detect a strong magnetic signal on CL, which is positive.
As shown in fig. 1(c), when a test sample containing no antigen is coated on the sample pad, the sample flows toward the adsorption pad G by capillary force. In this process, the antigen binds to the magnetic nanoparticle-labeled antibody to form a conjugate (Ag-MNPs-Ab). Due to competition limitation, the target hapten can capture flowing Ag-SMNPs-Ab in the detection line D (TL) and the control line E (CL), and the instrument can detect stronger magnetic signals on the detection line D (TL) and the control line E (CT), which is negative.
In order to detect the magnetic field intensity on a detection line D (TL) and a control line E (CL) in a paper to be tested, the invention adopts a magnetoresistive sensor using InSb single crystal as a magnetoresistive element, the magnetic field change can be detected by utilizing the magnetoresistive effect, the internal structure of the magnetoresistive sensor is shown in figure 2(a), the magnetoresistive sensor consists of two magnetoresistive devices (MR1, MR2) and a permanent magnet, the two magnetoresistances are connected in series, the permanent magnet applies a uniform magnetic field to the two MR devices, an output terminal is arranged at the connection part of the two MR devices, the voltage on the terminal is called as output voltage Vo, and when the input voltage V is inputiWhen applied across the MR device, the output voltage is approximately half the input voltage, the voltage being the median voltage. However, if magnetic fields of different strengths are applied to the two MR devices, the output and the median voltage will differ due to the difference in resistance values of the devices. For example, as shown in fig. 2(b), when a magnetic material passes through MR1, the magnetic field lines passing through MR1 increase, so that the resistance value increases more than MR2, and thus the output voltage is less than the median voltage, whereas if a strong magnetic field is applied to MR2, the output voltage will be greater than the median voltage.
It is assumed that the magnetic material moves at the front surface of the MR sensor. Fig. 3(d) depicts the output of the MR sensor as the magnetic material passes through the positions plotted in fig. 3(a) -3 (c). The arrows in fig. 3(d) indicate the response of this material in corresponding position with the MR sensor of the previous figure. As can be seen from the figure, the output is relatively flat when no magnetic material passes through; this is the median voltage. As the magnetic material moves upward through MR2, the output voltage increases relative to the median voltage. The output voltage reaches a maximum when it moves to the center of MR 2. When the magnetic material moves to the position intermediate MR1 and MR2, the output is the median voltage and the magnetic material continues to move. When it moves to the center of MR1, the output voltage drops to the lowest and finally returns to the median voltage. According to the principle, the magnetic test strip can be quantitatively analyzed.
Due to the nature of the sensor output (as shown in fig. 3 (d)), two waveforms are shown. To facilitate the design of the load circuit, the output signal is simplified by using a conventional first-order integration algorithm circuit, as shown in fig. 4 (a). Considering that the output signal of the sensor is very weak and the signal-to-noise ratio is low, a band-pass circuit is used to reduce noise and amplify the signal of the specific frequency component according to the specificity of the signal, such as a specific frequency component. A capacitor is added in a traditional first-order integration algorithm circuit, so that the circuit has a high-pass characteristic. Since the integrating algorithm circuit has a low-pass characteristic, a required second-order active band-pass filter is obtained, as shown in fig. 4 (b). In order to reduce the influence of unstable power supply and output resistance thermal noise, a differential amplifier is used to simulate interference by using a characteristic of a sampled voltage and two resistance-identical resistance sensors and use the two resistance-identical resistance sensors as input in the same direction. Finally, the circuit realizes filtering amplification of the signal.
The circuit part mainly comprises a magnetic resistance sensor, an analog front end, a central processing unit and a digital signal processing unit. Fig. 5(a) shows the functional modules of the system architecture. First, an equivalent circuit of the magnetoresistive sensor is given. Although the biological sample does not contain magnetic background noise, the magnetic noise still exists in the surrounding environment, and the raw signal acquired by the magnetic resistance sensor can also have larger noise interference. The analog front end adopts a two-stage operational amplifier circuit to process the signals detected by the sensor. The processed signals are collected by the ADC and converted into digital signals, stored in a FLASH of a central processing unit (singlechip), and then communicated with a digital signal processing unit (computer) through a serial port. The invention uses Python to establish a simple graphical user interface on a digital signal processing unit (computer) and can display, analyze and process signal waveforms.
The detection process of the system of the invention is briefly described below, the test paper which has undergone immunochromatography is placed on the test card seat 103, the central processing unit sends a corresponding instruction to the control circuit to control the stepping motor 102 and drive the transmission mechanism 104 to move, so that the magnetoresistive sensor 101 above the structure scans the whole test paper, the magnetic nanoparticle concentration information on the Test Line (TL) and the Control Line (CL) on the test paper is converted into an electric signal, the electric signal is amplified by the second-order active band-pass filter, converted into a digital signal by the analog-to-digital converter (ADC), collected and stored by the central processing unit, uploaded to the digital signal processing unit (computer) end through a serial port, and the waveform is displayed, analyzed and processed by using a graphic user interface established by Python.
In the present invention, a system mechanical structure (dimensions 98mm × 62mm × 78mm) having a structure shown in fig. 5(b) is employed. The main components are a magnetic resistance sensor 101, a stepping motor 102, a test card seat 103 and a transmission mechanism 104. The transmission mechanism comprises a gear plate 109 and a slide rail 1010, the magnetic resistance sensor 101 is fixed above the base 106, the paper to be tested 105 is placed on the test card seat 103, and the magnetic resistance sensor 101 can collect magnetic signals in the paper to be tested 105. In order to reduce the interference of the magnetic signal generated by the stepping motor 102 during operation with the system, the stepping motor 102 is designed to be as far away as possible from the magnetoresistive sensor 101, and the system circuit is placed in the base 106. The differential amplification filter circuit composed of two stages of operational amplifiers is used for eliminating the interference of common-mode signals in the environment and amplifying the signals. The filter is a band pass filter. The center frequency of the filter is adjusted, so that interference can be suppressed, and signals can be highlighted.
Referring to fig. 5(c), the mechanical structure will be described in detail below, the magnetic resistance sensor 101 is mounted on the magnetic resistance sensor support 107, the magnetic resistance sensor support 107 is clamped on the housing 108, the paper 105 to be tested is mounted in a groove in the middle of the test clamp seat 103, the test clamp seat 103 is mounted on the gear plate 109, the gear plate 109 is mounted on the slide rail 1010, the slide rail 1010 is mounted in a mounting groove in the middle of the housing 108, the test clamp seat 103 is clamped on two side plates of the housing 108, the stepping motor 102 is mounted on one side of the base 106, the housing 108 is mounted on the base 106, a gear of the stepping motor 102 is engaged with the gear plate 109, the gear plate 109 slides on the slide rail 1010, and the advance direction is limited by the slide rail 1010. All parts were secured by 3mm screws.
The system operation method comprises the following steps: after the paper 105 to be tested is subjected to immunochromatography reaction, the paper 105 to be tested is installed in a groove in the middle of the test card holder 103, a central processing unit sends a corresponding instruction, the stepping motor 102 is controlled to operate, the gear plate 109 is driven to move horizontally, the magnetoresistive sensor 101 fixed on the shell 108 through the magnetoresistive sensor support 107 scans the whole paper 105 to be tested, and then a detected signal is transmitted to the central processing unit for processing.
The invention can reduce the interference of the sample as much as possible by utilizing the characteristics of magnetism, can realize the quantitative detection of the detected sample, can realize the miniaturization of equipment and further promote the development of POCT.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.

Claims (6)

1. The magnetic immunity detection system is characterized by comprising four parts, namely a magnetoresistive sensor, an analog front end, a central processing unit and a digital signal processing unit;
the magneto-resistive sensor consists of two magneto-resistive devices and a permanent magnet, wherein the two magneto-resistive devices are connected in series, the permanent magnet uniformly applies a magnetic field to the two magneto-resistive devices, an output terminal I is arranged at the connection midpoint of the two magneto-resistive devices, and the output terminal I is connected with the analog front end;
the analog front end is a second-order active band-pass filter, the second-order active band-pass filter adopts a two-stage operational amplifier circuit to process signals detected by the magnetic resistance sensor, and the processed signals are input into the central processing unit;
the central processing unit is used for acquiring and converting the signal detected by the analog front end into a digital signal by the ADC, storing the digital signal in a FLASH of the central processing unit and communicating with the digital signal processing unit through a serial port;
and the digital signal processing unit is used for displaying, analyzing and processing the signal waveform.
2. The magnetic immunoassay system of claim 1, wherein the magnetic sensor further comprises a coupling circuit, the coupling circuit comprises a power supply, a resistor R11 and a resistor R12, an output terminal of the resistor R11 is connected in series with an input terminal of the resistor R12, an output terminal ii is provided at a connection point of the resistor R11 and the resistor R12, the output terminal ii is connected with the analog front end, one end of the power supply is connected with the input terminal of the resistor R11, and the other end of the power supply is connected with the output terminal of the resistor R12.
3. The immunodetection system of claim 2, wherein the second order active band-pass filter: the input Vin is connected with one end of a capacitor C1, the other end of the capacitor C1 is connected with one end of a resistor R1, the other end of a resistor R1 is connected with a minus port of an amplifier, one end of a resistor R2 and one end of a capacitor C2, the other end of the resistor R2 and the other end of the capacitor C2 are both connected with the output end of the amplifier, the VI is connected with one end of a resistor R3, the other end of the resistor R3 is connected with one end of a resistor R4 and a plus port of the amplifier, and the other end of the resistor R4 is grounded.
4. The immunodetection system of claim 3, wherein two second order active band-pass filters: an output terminal I of the magnetoresistive sensor is connected with an input end of the No. 1 second-order active band-pass filter and is connected with one end of a capacitor C1, an output of the No. 1 second-order active band-pass filter is connected with one end of a capacitor C3 of the No. 2 active band-pass filter, and an output terminal II of the coupling circuit is respectively connected with a resistor R3 of the No. 1 second-order active band-pass filter and a resistor R7 of the No. 2 second-order active band-pass filter.
5. The immunodetection system of claim 1, further comprising a magneto resistive sensor mounted on a magneto resistive sensor support, the magneto resistive sensor support is clamped on the housing, the paper to be tested is mounted in a groove in the middle of the test clamping seat, the test clamping seat is mounted on a gear plate, the gear plate is mounted on a slide rail, the slide rail is mounted in a mounting groove in the middle of the housing, the test clamping seat is clamped on two side plates of the housing, the stepping motor is mounted on one side of the base, the housing is mounted on the base, a gear of the stepping motor is meshed with the gear plate, the gear plate slides on the slide rail, the advancing direction is limited by the slide rail, and the analog front end and the central processing unit are both placed in the base.
6. The use method of the magnetic immunoassay system is characterized by comprising the following steps:
step 1, performing immunochromatography reaction on paper to be tested;
step 2, installing the paper to be tested in the groove in the middle of the test card holder, sending a corresponding instruction by the central processing unit, controlling the stepping motor to operate, driving the gear plate to move horizontally, scanning the whole paper to be tested by the magnetic resistance sensor fixed on the shell through the magnetic resistance sensor support, and transmitting the detected signal to the central processing unit for processing;
and 3, storing the signal waveform in a FLASH of the central processing unit, communicating with the digital signal processing unit through a serial port, and establishing a graphical user interface on the digital signal processing unit to display, analyze and process the signal waveform.
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