KR101235845B1 - System for signal detection of specimen using magnetic resistance sensor and Detecting Method of the same - Google Patents

Abstract

The present invention relates to a detection system using a magnetoresistive sensor, and more particularly, to detect a magnetic signal for a sample combined with magnetic particles by using a magnetoresistance (MR) sensor and to generate and analyze the magnetic component in the detector and the detector. And an amplifying unit for amplifying the magnetic signal, and a signal processing unit for removing a noise signal by differentially detecting a signal in the presence and absence region of the magnetic particles from the detection signal passing through the amplification unit.
According to the present invention, while providing a signal detection system of the specimen using a magnetoresistive sensor, by applying the direction of the magnetic field applied to the magnetoresistive sensor in the Y-axis direction and Z-axis direction of the magnetoresistance sensor to maximize the sensitivity performance of the sensor In particular, the signal processing unit is composed of a noise reduction circuit for removing the noise by separating the signal generated during the scan of the sample has the effect of minimizing the noise of the signal due to noise and vibration.

Description

System for signal detection of specimen using magnetic resistance sensor and Detecting Method of the same}

The present invention relates to a high sensitivity inspection system and method for efficiently removing noise by using a magnetoresistive sensor and quantitatively measuring magnetic particles.

The recent entry into an aging society and the growing desire for healthy life expand the market for portable health care systems and provide biosensors that can analyze, measure, diagnose, and search for bioactive and chemical substances. The importance is increasing.

Since biosensors use selective reactions between molecules, they should be able to reduce interference by other substances, distinguish sensitive substances with high sensitivity, enable mass production by lowering production costs, and speed up response. It needs to be monitored in real time everywhere.

Until now, biosensor development research has been conducted various research and development efforts as a tool for quantifying or analyzing the concentration of a specific bioactive substance.

The market is already formed in the form of portable measuring instruments that can be used in the medical and environmental industries, such as blood glucose meters, blood ion analyzers, and biological sample research devices, and automated analysis devices for research purposes, and clinical and medical diagnostics and food hygiene. Wide application is expected in the fields of agriculture, agriculture and fine chemicals.

In recent years, as biochip technologies such as DNA chips and protein chips are rapidly being developed as a means of identifying genetic information of humans, diagnosing diseases, preventing medicine, and searching for new drug candidates, the functions of biosensors go beyond simple analysis. The functions of diagnosis and mass retrieval are emphasized.

Such a biosensor uses a magnetic particle detection device using a magnetoresistance sensor (Magneto resistance, Hall sensor) to detect a substance. The magnetic particle detection device must use a complex power source of alternating current and direct current power. In addition, since the sensitivity of the magnetoresistive sensor is not good, the sensor must be driven by applying a strong magnetic field in the vertical direction. In addition, since the input signal of the AC waveform is used, it is sensitive to external noise and has a difficult problem of converting a reference voltage using a variable resistor.

Therefore, complex system equipment must be configured to drive a magnetoresistive sensor (hall sensor), which is sensitive to external noise, and requires a lot of power, and thus has a significant disadvantage in cost.

The present invention has been made to solve the above problems, an object of the present invention is to provide a signal detection system of a specimen using a magnetoresistive sensor, the direction of the magnetic field applied to the magnetoresistive sensor in the Y-axis direction of the magnetoresistive sensor Sensitivity performance of the sensor can be maximized by applying in the direction of Z and Z. In particular, the signal processing unit is composed of a noise reduction circuit that removes noise by classifying signals generated during scanning of a sample. The present invention provides a detection system capable of minimizing noise and a detection method using the same.

As a means for solving the above problems, the present invention is a detector for detecting a magnetic signal for a sample combined with magnetic particles with a magnetic resistance (MR) sensor to separate and analyze the magnetic component; and generated in the detector An amplifier for amplifying a magnetic signal; And a signal processor for removing a noise signal by differentially detecting a signal passing through the amplification unit in the presence and absence regions of the magnetic particles.

The signal processing unit may further include: a control unit configured to measure and store a first signal obtained by scanning a portion free of magnetic particles in the sample fixing unit including the sample and a second signal which is a scan signal at a portion having magnetic particles; And a control processor configured to differentially differentiate the first and second signals from the control unit to form a third signal from which a noise signal due to noise and vibration is removed.

The signal processor may further include an operation processor configured to digitize and process the third signal, and a signal display configured to display the digitized signal.

The detector according to the present invention may be configured to include an external magnetic field applying device for applying an external magnetic field to the magnetoresistive sensor in at least one direction, in which case the external magnetic field applying device is provided to the magnetoresistive sensor. A first application unit for applying a magnetic field in a horizontal direction (Y axis) in one direction; And a second application unit configured to apply a magnetic field to the magnetoresistive sensor in a vertical direction (Z axis) in a second direction.

In addition, the specimen fixing unit having the specimen may be a measurement cartridge or membrane to which the biomaterial containing the antibody is fixed.

The first application unit in the external magnetic field applying apparatus according to the present invention, the magnetic field generating unit may be any one or a plurality selected from the solenoid coil, Helmholtz coil, electromagnet yoke, permanent magnet, the second The applying unit may include any one or a plurality of magnetic field generating units selected from solenoid coils, Helmholtz coils, and electromagnet yokes.

In addition, the magnetic field generated in the second application unit may be formed by a direct current (DC) current.

In addition, the magnetoresistive sensor according to the present invention may be a giant magnetoresistance (GMR) sensor.

The detection system according to the present invention described above can implement the measurement of the specimen through the following process.

Specifically, the detection method of performing a quantitative measurement of the sample by the magnetic resistance sensor by applying an external magnetic field to the magnetic particles, comprising the steps of: scanning the portion of the sample containing the sample free of magnetic particles and storing the first signal; Measuring and storing a second signal, which is a scan signal in a portion where magnetic particles of the sample are present; And differentially dividing the first and second signals to form a third signal from which a noise signal due to noise and vibration is removed.

In this case, the magnetic field is applied to the sample by applying an induction magnetic field to the sample in the horizontal direction (Y axis) of the magnetoresistive sensor, and magnetizing the magnetic particles while fixing the movement of the sample to the measurement position. A DC magmetic field may be applied in the vertical direction (Z axis) of the magnetoresistive sensor.

Furthermore. The range of the horizontal (Y-axis) magnetic field or the range where the magnetoresistive sensor (MR) can react is formed at 2 to 30 gauss, and the magnetic field applied to the vertical direction (Z-axis) is 1200 to 1800 gauss ( Gauss) can be formed in the range.

According to the present invention, while providing a signal detection system of the specimen using a magnetoresistive sensor, by applying the direction of the magnetic field applied to the magnetoresistive sensor in the Y-axis direction and Z-axis direction of the magnetoresistance sensor to maximize the sensitivity performance of the sensor In particular, the signal processing unit is composed of a noise reduction circuit for removing the noise by separating the signal generated during the scan of the sample has the effect of minimizing the noise of the signal due to noise and vibration.

In addition, by using a non-contact giant magneto-resistance sensor (Giant Magneto Resistance) it is possible to perform efficient bio-diagnosis through sensing the sample. Therefore, the membrane used for Point of Care Testing (POCT) can be installed in the sample diagnostic kit to develop a measuring instrument for effective membrane measurement.It uses only DC power voltage when driving the system, compared to conventional Hall sensors. It can be driven with less power, resulting in economic advantages.

Fig. 1 is a conceptual diagram for explaining the sensing principle of the magnetoresistive sensor used in the present invention.
2 is a block diagram illustrating a detection system using a magnetoresistive sensor according to the present invention.
Figure 3a shows an embodiment of a detector according to the present invention.
3b and 3c show a conceptual diagram of a GMR sensor as an embodiment of the magnetoresistive sensor according to the present invention.
4A and 4B illustrate the operation of the signal processor in the detection system according to the present invention shown in FIG.
FIG. 5 is a diagram illustrating result values of a signal processor performed in FIGS. 4A and 4B.

Hereinafter, with reference to the accompanying drawings will be described in detail the configuration and operation according to the present invention. In the description with reference to the accompanying drawings, the same components are given the same reference numerals regardless of the reference numerals, and duplicate description thereof will be omitted. The terms first, second, etc. may be used to describe various components, but the components should not be limited by the terms. The terms are used only for the purpose of distinguishing one component from another.

The present invention mounts magnetic particles to biomaterials on POCT cartridges or strips used for measuring biomaterials (antibodies or samples) in a diagnostic device using magnetic effects, and efficiently removes noise from magnetic signals generated during detection. It is an object of the present invention to provide a diagnostic system capable of precisely detecting low concentration of magnetic particles by removing unnecessary noise from an output signal.

1 is a conceptual diagram illustrating a sensing principle of a magnetoresistive sensor used in the present invention. However, for convenience of description, the sensing principle using a giant magneto resistance (GMR) of the magnetoresistive sensor will be described as an example.

This shows a spin-valve type Giant Magneto Resistance (GMR) device. As shown, the magnetoresistive sensor has a nonmagnetic metal layer sandwiched between two ferromagnetic metal layers. The magnetic force of the ferromagnetic metal layer of the first layer is fixed, and the magnetic force of the ferromagnetic material of the second layer is variably adjusted. When the first layer and the magnetic force are parallel, the principle that only electrons spin-oriented in a specific direction passes through the conductor. That is, according to the alignment of the magnetization directions of the two ferromagnetic layers, a difference in electrical resistance, or a potential difference, induced inside the material is generated and recognized as a digital signal. The case where an interlayer material is a conductor corresponds to a GMR device.

2 is a block diagram illustrating a detection system using a magnetoresistive sensor according to the present invention (hereinafter referred to as a 'detection system').

The detection system according to the present invention detects a magnetic signal for a sample combined with magnetic particles with a magnetic resistance (MR) sensor 130 and separates and analyzes the magnetic component into a magnetic component and the magnetic generated by the detector. And an amplifying unit 140 for amplifying the signal and a signal processing unit 200 for removing noise signals by differentially detecting signals in the presence and absence regions of the magnetic particles through the detection signal passing through the amplification unit.

The detector 100 according to the present invention includes a magnetoresistance (MR) sensor 130 and a first direction and a second direction of the magnetoresistive sensor 130, which detect magnetic components of a sample 122 to which magnetic particles are coupled. And an external magnetic field applying device 110 for applying a directional external magnetic field.

That is, the external magnetic field applying device applies a magnetic field to the magnetoresistive sensor 130 in the first direction and a magnetic field in the vertical direction in the second direction to the magnetoresistive sensor 130. And a second applying unit 112 to apply.

Mounting the sample to the sample fixing unit 121 through this basic structure, applying an external magnetic field from the external magnetic field applying device 110, coupled with a magnetic component (magnetic particles) in the magnetoresistive sensor 130 It detects the magnetic signal on the sample and separates and analyzes it into electrical components. Magnetic particles may have a magnetization value of 10 ~ 100emu / g. In this case, the magnetic particles may have superparamagnetism or paramagnetism. In addition, the specimen fixing unit 121 for fixing the specimen 121 may be a measurement cartridge or a membrane. The sample is fixed to form a measurement unit 120 including a sample fixing unit.

As described above, the detection device uses external application devices 111 and 112 for applying a magnetic field to the magnetoresistive sensor in at least one direction so that the intensity of the magnetic force received by the magnetic particles in the biomaterial is the sum of the applied magnetic fields in the horizontal and vertical directions. Therefore, it is possible to improve the sensitivity by increasing the magnetization power of the biomaterial.

The signal detected by the magnetoresistive sensor 130 is amplified by the amplifier 140, and the noise signal is removed from the signal processor 200 described above to detect the correct signal. That is, the signal processing unit 200 is a first signal obtained by scanning a portion free of magnetic particles in the sample fixing unit 121 including the specimen 122 and a second signal which is a scan signal in the portion having magnetic particles. The control unit 210 for measuring and storing the control unit 210 and the control unit 210 to differentially differentiate the first and second signals to form a third signal from which the noise signal due to noise and vibration are removed. And 220.

In addition, the signal processor 200 may further include an operation processor 230 for digitizing and processing the third signal and a signal display unit 240 for displaying the digitized signal.

Hereinafter, the operation of the above-described detection system will be described through a specific implementation example.

Figure 3a shows an embodiment of a detector according to the present invention, as shown, the sample to be detected, the sample fixing unit 121 for fixing the sample, and applying a magnetic field from the outside to the biomaterial External magnetic field applying device (111, 112) and a magnetoresistive sensor (130).

Implement the configuration of applying the external magnetic field in the first direction and the second direction of the magnetoresistive sensor 130, the first direction serves to create a horizontal magnetic field to hold the initial position of the magnetic field sensor and the peripheral By blocking the noise of the sensor can improve the performance of the sensor. Specifically, the first direction and the second direction are particularly preferably provided in the first application unit 111 for applying the magnetic field in the horizontal direction (Y-axis) which is the first direction to the magnetoresistive sensor, and the magnetoresistive sensor. It is preferable to include a second application unit 112 for applying a magnetic field in the vertical direction (Z axis) in two directions. Of course, the above-mentioned vertical direction in the horizontal direction does not necessarily mean only perpendicular to the elevation of the magnetoresistive sensor, but includes a concept that includes a certain degree of fluidity in the incident direction. In addition, the second application unit 112 is preferably implemented to be able to change the magnetic field through the current. The range of the horizontal (Y-axis) magnetic field or the range where the magnetoresistive sensor (MR) can react is formed at 2 to 30 gauss, and the magnetic field applied to the vertical direction (Z-axis) is 1200 to 1800 gauss ( Gauss) can be formed in the range.

Therefore, the first application unit 111, the magnetic field generating unit can be implemented in a configuration that applies a fixed magnetic field consisting of any one or more selected from the solenoid coil, Helmholtz coil, electromagnet yoke, permanent magnet. The second application unit 112 may include any one or a plurality of magnetic field generating units selected from solenoid coils, Helmholtz coils, and electromagnet yokes.

In addition, the magnetoresistive sensor 130 of the present invention is a normal magnetoresistance (OMR) sensor, anisotropic magnetoresistance (AMR) sensor, a giant magnetoresistance (GMR) sensor, a super-magnetism ( Colossal Magnetoresistance (CMR) sensor, Tunneling Magnetoresistance (TMR) sensor, MJT (Magnetic Tunneling Junction) sensor, Planar Hall Resistance (Planar Hall Resistance) sensor is preferably used any one selected from. Particularly preferably, a giant magnetoresistance (GMR) sensor may be used.

3B and 3C illustrate a conceptual diagram of a GMR sensor as one embodiment of a magnetoresistive sensor according to the present invention, which is a conceptual diagram of a magnetoresistive sensor in a detection device to which the magnetoresistive sensor is applied. In the conceptual diagram shown, the arrow is centered on a sensor composed of a stack of thin film materials, and the horizontal direction (X axis direction) of the thin film material, the horizontal direction (Y axis direction) of the thin film material, and the vertical direction (Z axis direction) of the thin film material. Indicates. Such a GMR sensor is very strong only in the magnetic field perpendicular to the sensor (Y axis) and slightly in the direction parallel to the sensor (X axis), while in the direction perpendicular to the sensor (Z axis). It is not affected at all. In addition, for the magnetic field in the Y-axis direction, it is possible to adjust the bias (biasing) within a unique linear range (linear range).

Therefore, the system design for the maximum performance of the GMR sensor is applied by applying a DC magnetic field in the Z-axis direction to saturate the superparamagnetic magnetic particles and applying the magnetic field in the Y-axis direction to improve the sensitivity performance of the sensor. It is essential to have maximum deflection control. In this case, the application of the magnetic field in the Y-axis direction is very effective in improving the signal-to-noise ratio by using an induced magnetic field generated through a DC current.

4A and 4B illustrate the operation of the signal processor in the detection system according to the present invention shown in FIG.

For example, a measurement kit using a spin valve type GMR element as shown in FIG. 3C for implementing the present operation may be provided with an electrode pattern by installing at least one GMR element of a biosensor spin valve type. . In this case, the GMR element used has a volume of 0.3 mm, 0.5 mm, 1.0 mm or 0.25 mm, 1.0 mm, 1.5 mm and has a saturation field of 3 to 150 Gauss, and a sensitivity of 0.9 to 18 mV / V-. 0e will be used. The GMR device itself interface was supplied using a Wheatstone bridge, and the power supply voltage was 5V. The sensing element was measured in the range of several Ω to several kilowatts.

For example, when using a scan method using a motor to measure a magnetization value that changes in time to measure the magnetic particle band of the sample in the detector shown in Figure 3a, the output signal is the noise and vibration generated during the scan Since the signal from the sample is mixed with the noise signal caused by the signal, it is difficult to obtain an accurate signal, especially when it is a low concentration of magnetic particles, it is difficult to confirm the signal accurately.

Accordingly, as shown in FIG. 4A, the vibration control (first signal) generated during scanning is controlled by scanning the scanner (SC) without the magnetic particles in the sample fixing unit 120 including the sample. Store in unit (210 in FIG. 2). Thereafter, as shown in FIG. 4B, vibration noises generated by rescanning portions having magnetic particles forming the magnetic bands B and signals (second signals) generated from the magnetic particles on the specimen are stored.

Subsequently, when the first signal and the second signal are different from each other through the control processor 220 of FIG. 2, a value corresponding to the vibration noise generated during the scan is removed to remove the signal portion having the midnight particles on the sample ( Only the third signal is left.This is defined as a making operation, and this removes the noise signal due to the noise and vibration generated during the scan, and the signal from the magnetic particles on the pure sample is measured to obtain an accurate signal. It becomes possible.

Subsequently, when signal processing is performed through the arithmetic processing unit, an accurate signal in which noise is reduced and removed can be displayed on the signal display unit 240 (in FIG. 2).

FIG. 5 is a diagram illustrating result values of a signal processor performed in FIGS. 4A and 4B.

In general, a signal waveform for detecting low concentration magnetic particles of a detection signal is buried in noise generated when a signal of low concentration magnetic particles is scanned so that an accurate value is not detected. That is, it is difficult to distinguish which value is the signal of the magnetic particles. This makes it difficult to analyze because the calculation of the signal and the reference point for the surely matched analysis are not set.

As shown in (a) shown in FIG. 4b, the result of scanning the portion with magnetic particles is shown, (b) is the result of scanning the portion without magnetic particles as shown in FIG. 4a, and (c) described above. Figures show the result of making a work by differentially (a) and (b). In this case, it can be seen that the apparent signal peak can be confirmed for the low concentration magnetic particles.

Therefore, due to the configuration of the signal processing unit in the detection system according to the present invention, in order to eliminate the inaccuracy of detection that occurs in the manner of using a scanner using a motor to read the information of the specimen (sample), it is generated during the scan of the sample. The noise of the signal due to the noise and vibration can be minimized. This can be applied in various magnetoresistive detectors, in which the scanning speed varies depending on the characteristics of the sample, and magnetic particles can be detected more effectively when using a giant magnetoresistive sensor having excellent MR ratio and sensitivity. In addition, since only the DC power supply voltage is used to drive the detection system, it can be driven even at low power, which is advantageous in terms of cost.

In the foregoing detailed description of the present invention, specific examples have been described. However, various modifications are possible within the scope of the present invention. The technical idea of the present invention should not be limited to the embodiments of the present invention but should be determined by the equivalents of the claims and the claims.

110: external magnetic field application device
111: first authorization unit
112: second authorization unit
120: specimen fixing unit
121: sample (sample)
130: magnetoresistive sensor
140: amplification unit
200: signal processing unit
210: control unit
220: control processing unit
230: arithmetic processing unit
240: signal display unit

Claims (13)

A detector that detects a magnetic signal for a sample combined with magnetic particles with a magnetic resistance (MR) sensor and separates and analyzes it into magnetic components; and
An amplifier for amplifying the magnetic signal generated by the detector; And
A signal processing unit for removing noise signals by differentially detecting a signal passing through the amplifying unit in the presence and absence regions of magnetic particles;
Characterized in that the signal detection system of the specimen using a magnetoresistive sensor.
The method according to claim 1,
The signal processing unit,
A control unit for measuring and storing a first signal obtained by scanning a portion free of magnetic particles in a sample holding unit provided with the specimen and a second signal which is a scan signal at a portion having magnetic particles;
A control processor configured to differentially differential the first and second signals from the control unit to form a third signal from which noise signals due to noise and vibration are removed;
Characterized in that the signal detection system of the specimen using a magnetoresistive sensor.
The method according to claim 2,
The signal processing unit,
And a signal processing unit for displaying the digitized signal and an arithmetic processing unit for digitizing and processing the third signal.
4. The method according to any one of claims 1 to 3,
The detector device,
And an external magnetic field applying device for applying an external magnetic field to the magnetoresistive sensor in at least one direction.
The method of claim 4,
The external magnetic field applying device,
A first application unit for applying a magnetic field to the magnetoresistive sensor in a horizontal direction (Y axis) in a first direction;
A second application unit for applying a magnetic field to the magnetoresistive sensor in a vertical direction (Z axis) in a second direction;
Characterized in that the signal detection system of the specimen using a magnetoresistive sensor.
The method according to claim 5,
Specimen fixing unit provided with the specimen,
A signal detection system for a specimen using a magnetoresistive sensor, characterized in that the measuring material or the membrane is fixed to the biomaterial containing the antibody.
The method according to claim 5,
The first application unit, characterized in that the magnetic field generating unit is applied to a fixed magnetic field consisting of any one or more selected from the solenoid coil, Helmholtz coil, electromagnet yoke, permanent magnet Sample signal detection system.
The method according to claim 5,
The second application unit, the magnetic field generating unit is any one or more selected from the solenoid coil, Helmholtz coil, electromagnet yoke is applied to the variable magnetic field, characterized in that the signal of the specimen using a magnetoresistive sensor Detection system.
The method according to claim 8,
The magnetic field generated in the second application unit is formed by a direct current (DC) current, the signal detection system of the specimen using a magnetoresistive sensor.
The method according to claim 5,
The magnetoresistive sensor is a giant magnetoresistance (GMR) sensor, characterized in that the specimen signal detection system using a magnetoresistive sensor.
In the method of detecting a signal of a sample by applying an external magnetic field to the magnetic particles to perform a quantitative measurement of the sample with a magnetoresistance sensor,
Scanning the portion free of magnetic particles in the sample containing the sample and storing the first signal;
Measuring and storing a second signal, which is a scan signal in a portion where magnetic particles of the sample are present;
Differentially dividing the first and second signals to form a third signal from which a noise signal due to noise and vibration is removed;
Characterized in that the signal detection method of the specimen using a magnetoresistive sensor.
The method of claim 11,
The method of applying a magnetic field to the sample,
Applying an induction magnetic field to the specimen in the horizontal direction (Y axis) of the magnetoresistive sensor, and magnetizing the magnetic particles with the movement of the specimen fixed at the measurement position.
A method of detecting a signal of a specimen using a magnetoresistive sensor, characterized in that it is implemented to apply a direct current (DC magmetic field) in the vertical direction (Z axis) of the magnetoresistive sensor.
The method of claim 12,
The range of the horizontal (Y-axis) magnetic field or the range in which the magnetoresistive sensor MR can react is formed to be 2 to 30 Gauss,
The magnetic field applied to the vertical direction (Z axis) is formed in the range of 1200 ~ 1800 Gauss (Gauss), the signal detection method of the specimen using a magnetoresistance sensor.

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