KR20130061016A - Apparatus for analyzing bio material using magnetic sensing method - Google Patents

Abstract

PURPOSE: A bio material analyzing device using a magnetic sensing method is provided to adjust a position of a permanent magnet included in a magnet field applying device, thereby controlling the intensity and a direction of a magnetic field applied to a magnetic sensor. CONSTITUTION: A bio material analyzing device using a magnetic sensing method comprises a magnetic field applying unit and a magnetic sensor(150). The magnetic field applying unit senses a changes in a magnetic field applied to the magnetic field applying unit caused by magnetic materials attached by a receptor collecting target bio materials. The intensity of the magnetic field applied by the magnetic field applying unit and an angle of the magnetic sensor are adjustable.

Description

Apparatus for analyzing bio material using magnetic sensing method

The present invention relates to a biomaterial analysis device and a magnetic sensor applicable thereto, and more particularly, to a biomaterial analysis device and a magnetic sensor applicable thereto for determining a concentration of a biomaterial in a sample using a magnetic sensor.

Analysis of trace biomaterials is one of the most important challenges in biotechnology, medicine and chemistry. In this respect, much research has been conducted to develop easier analytical methods, and the development of innovative analytical methods is very influential enough to change the academic trends in biotechnology and related fields.

Biosensors using strips are widely used in pregnancy diagnostic strips through urination analysis, urine test strips, and strips for diagnosing myocardial infarction using fluids of patients in the field.

The strip consisting of the membrane is rich in porosity such as nitrocellulose (NC) to maximize the surface area of the stationary phase, and then allows chemicals, especially biomolecules, etc. mixed in the test solution to separate or react with each other as they move through the membrane. It is useful for detecting specific biomolecules. In order to recognize the presence of specific biomolecules, an enzyme reaction is used to observe the characteristics of occurrence, or to label fluorescence to observe fluorescence, or to label nanoparticles and to read optical property changes to analyze the substance to be detected.

Meanwhile, in order to detect finer concentrations and to quantitatively analyze, equipment for detecting labeling materials with photodetectors, CCD cameras, image sensors, fluorescent scanners, and the like has been developed.

However, a diagnostic device for analyzing fluorescence is expensive, and a device using a camera sensor and an image sensor has a disadvantage of low sensitivity, and a high sensitivity camera sensor and an image sensor have a disadvantage of expensive sensor cartridge or device.

The present invention has been made to solve the above problems, and as a method of labeling biomolecules using magnetic nanoparticles and using magnetic sensors (eg, GMR sensors, etc.), an object of the present invention is to provide a target biomaterial. The present invention provides a biomaterial analysis device capable of detecting concentration of a target biomaterial by detecting a change in a magnetic field caused by magnetic nanoparticles attached to a capture receptor, and a magnetic sensor signal processing circuit applicable thereto.

According to an embodiment of the present invention, a biomaterial analyzing apparatus includes: a magnetic field applying unit; And a magnetic sensor for detecting a change in the magnetic field applied to the magnetic field applying unit by the magnetic nanoparticles attached to the receptor capturing a target biomaterial, wherein the magnetic field applied by the magnetic field applying unit and the magnetic sensor The angle is adjustable.

The magnetic sensor may maintain a specific angle with a magnetic field applied by the magnetic field applying unit, and the specific angle may be an angle that causes the output of the magnetic sensor according to the change of the magnetic field to be in a linear sensitivity region. have.

The magnetic sensor may include a Wheatstone bridge circuit including two reference resistors facing each other and two magnetic resistors facing each other, and a voltage change between two opposite nodes of the Wheatstone bridge circuit. May be output as a result of the magnetic field change detection.

In addition, the biological material analysis apparatus according to an embodiment of the present invention, further includes a variable resistor connected in parallel to any one of the two reference resistors, the resistance value of the variable resistor, by the magnetic field applying unit The unbalanced state of the Wheatstone bridge circuit by the applied magnetic field may be a resistance value.

The magnetic nanoparticles attached to the receptor capturing the target biomaterial are provided on a strip into which a sample obtained from the human body is injected, and the magnetic nanoparticles attached to the receptor capturing the target biomaterial included in the sample. Can be.

As described above, according to the present invention, the magnetic sensor detects the change in the magnetic field caused by the magnetic nanoparticles attached to the receptor for capturing the target biomaterial, and adjusts the position of the permanent magnet constituting the magnetic field applying device. It is possible to adjust the strength and direction of the applied magnetic field.

In addition, by connecting the variable resistor in parallel to one of two reference resistors and two of the two magnetic resistors constituting the magnetic sensor, the variable resistance value is adjusted when an external magnetic field is applied to balance the Wheatstone bridge to zero the output value. In this way, the magnetic sensor signal output by the external magnetic field can be eliminated, and the Wheatstone bridge output voltage caused by the change of the magnetic resistance due to the stray field caused by the sexual nanoparticles can be amplified at a high magnification. By discreetly performing the concentration of particles, it is possible to lay the groundwork for a faithful analysis of the concentration of biomaterials.

1 to 4 is a perspective view showing the manufacturing process of the biomaterial analysis apparatus according to an embodiment of the present invention,
5 is a detailed view of a strip holder,
6 shows a structure and an equivalent circuit of a magnetic sensor;
7 is a magnetic sensor circuit diagram in which a variable resistor is connected in parallel to a reference resistance of the magnetic sensor shown in FIG. 6;
8 is a graph showing an output voltage change of the magnetic sensor (Wheatstone bridge circuit) of FIG. 6 against a change in external magnetic field strength;
9 is a view provided to explain the GMR characteristic;
FIG. 10 is provided for the description of the magnetic sensor output change according to the directions of the magnetic fields applied and the GMRs of the magnetic sensor, and
Fig. 11 is a diagram provided for further explanation on the determination of the magnetic sensor and the magnetic field strength and direction.

Hereinafter, with reference to the drawings will be described the present invention in more detail.

1 to 4 is a perspective view showing the manufacturing process of the biomaterial analysis apparatus according to an embodiment of the present invention.

As shown in FIG. 1, the biomaterial analysis apparatus includes a horizontal base plate 110, a vertical base plate 120, fixing parts 131, 132, and 133, permanent magnets 141 and 142, and a magnetic sensor. 150.

The horizontal base plate 110 is a means for supporting the vertical base plate 120, and fixing parts 131, 132, and 133 are installed and fixed to the vertical base plate 120.

The permanent magnet-1 141 is installed and fixed to the fixed part-1 131, and the installation position of the permanent magnet-1 141 is variable on the fixed part-1 131. Similarly, the permanent magnet-2 142 is installed and fixed to the fixed part-2 132, and the installation position of the permanent magnet-2 142 is variable on the fixed part-2 132.

On the other hand, the magnetic sensor 150 is installed and fixed to the fixing unit-3 (133), the installation position of the magnetic sensor 150 is variable on the fixing unit-3 (133).

The permanent magnet-1 141 and the permanent magnet-2 142 are means for applying a magnetic field to the magnetic sensor 150. The permanent magnets 141 and 142 may be replaced with electromagnets, but the permanent magnets 141 and 142 may be implemented as permanent magnets for stable magnetic field application.

FIG. 2 shows posts 161 and 162 installed on the horizontal base plate 110 of the biomaterial analysis apparatus shown in FIG. 1, and FIG. 3 shows a strip holder mounting portion on the posts 161 and 162. The state which installed 170 was shown.

4 illustrates a mechanism in which the strip holder 180 is mounted on the strip holder mounting unit 170. As shown in FIG. 4, the strip holder 180 slides along the rails 171 and 172 formed in the strip holder mounting portion 170, and is fixed by the fixing means 173 and 174 to fix the strip holder mounting portion 170. Is mounted on.

All materials of the strip holder mounting portion 170 including the rails 171 and 172 and the fixing means 173 and 174 are preferably made of nonmagnetic material. This is to prevent the magnetic field generated by the permanent magnets 141 and 142 from being changed by the strip holder mounting unit 170.

5 is a detailed view of the strip holder 180. As shown in FIG. 5, the strip holder 180 includes a main body 181, a handle 182, and a sample injection unit 183, and a strip 184 is mounted on the strip holder 180. In addition, when the strip holder 180 is mounted while being slid to the strip holder mounting unit 170, one side of the housing is opened so that the magnetic sensor 150 and the test area 185 are opened so as not to be caught by the protruding magnetic sensor 150. Can be in close contact.

The sample obtained from the human body injected through the sample injector 183 is transferred to the strip 184. The test region 185 of the strip 184 has a receptor material attached thereto, and a material in which magnetic nanoparticles and a receptor material are combined near the sample inlet 183 is combined with the target biomaterial included in the sample. It flows along the strip and is captured and fixed with magnetic nanoparticles in the test region 185 where the receptor is formed.

Here, the target biomaterial may be an antigen and the receptor may be an antibody, but may be embodied in other materials.

If the sample obtained from the human body contains a large number of target biomaterials, the number of receptors trapped in the test region 185 of the test region strip 184 increases, and ultimately, the magnetic nanoparticles in the test region 185 of the strip 184. It will increase.

Referring to FIG. 4, it can be seen that the test area 185 of the strip 184 mounted to the strip holder 180 is adjacent to the magnetic sensor 150. Thus, the change of magnetic nanoparticles in the test region 185 of the strip 184 causes a change in the magnetic field sensed by the magnetic sensor 150, which magnetic sensor 150 changes the magnetic field in the sample. Outputs the target biomaterial concentration at.

Hereinafter, the magnetic sensor 150 will be described in detail. 6 is a diagram illustrating a structure and an equivalent circuit of the magnetic sensor 150. As shown in FIG. 6, the magnetic sensor 150 includes a Wheatstone bridge circuit including two reference resistors facing each other and two Giant Magneto-Resistances (GMRs) facing each other. Bridge circuit).

The reference resistors are shielded so that the resistance value is not affected by an external magnetic field. GMR is a resistance whose resistance value changes with a change in an external magnetic field, and its detailed structure will be described later in detail.

A bias power source is applied to the upper and lower nodes of the Wheatstone bridge circuit. The opposite left and right nodes of the Wheatstone bridge circuit are connected to the output terminals, and the voltage between the output terminals changes as the resistance values of the GMRs change.

On the other hand, since the resistance values of the GMRs are changed by an external magnetic field, the voltage between the output terminals of the Wheatstone bridge circuit is changed according to the change of the external magnetic field. Specifically, the voltage increases as the intensity of the external magnetic field increases.

Meanwhile, around the GMR, flux concentrators are provided for concentrating a magnetic field applied from the outside to the GMR, and the flux concentrators are preferably implemented with a material easily magnetized to an external magnetic field.

FIG. 7 shows a circuit diagram of a magnetic sensor having a structure different from that shown in FIG. 6. In FIG. 7, an amplifier OP Amp. Which amplifies the voltage between the bias power supply Vbias and the output terminals of the Wheatstone bridge circuit is explicitly shown.

In FIG. 7, it can be seen that the variable resistor Rad is connected in parallel to one of two reference resistors Rb provided in the Wheatstone bridge. The variable resistor Rad is a resistor for adjusting the unbalanced state of the Wheatstone bridge circuit by the magnetic field applied by the permanent magnets 141 and 142 to an equilibrium state.

Although the Wheatstone bridge circuit is designed to achieve an equilibrium state [(Rgmr_a) (Rgmr_b) = (Ra) (Rb)], it is unbalanced by the permanent magnets 141 and 142 [(Rgmr_a) (Rgmr_b) ≠ (Ra (Rb)]. This unbalance is due to the horizontal magnetic field component formed by the permanent magnets 141 and 142.

When the Wheatstone bridge circuit transitions to an unbalanced state, the voltage magnitude between the output terminals of the Wheatstone bridge circuit is highly dependent on the vertical magnetic field component, resulting in a very high initial voltage value.

Therefore, since the sensitivity of the magnetic field change due to the 'change of the amount of magnetic material in the test region 185 of the strip 184' is relatively decreased, it causes a decrease in sensitivity (resolution) of the target biomaterial concentration measurement. It is desirable to adjust the value close to '0'.

Therefore, in a situation where a vertical magnetic field is applied by the permanent magnets 141 and 142, the Wheatstone bridge circuit is required to be in equilibrium, and the resistance value of the variable resistor Rad is determined by the permanent magnets 141 and 142. It is determined by the resistance value for adjusting the unbalanced state of the Wheatstone bridge circuit by the initial magnetic field applied by

That is, it is preferable to determine the resistance value of the variable resistor Rad so that the following expression is satisfied.

[(Rgmr_a) (Rgmr_b) = (Ra) (Rb∥Rad)]

8 is a graph showing a change in output voltage of a Wheatstone bridge circuit against a change in external magnetic field strength. As shown in FIG. 8, although the GMR varies depending on the type (AA002-02 Type, AA004-02 Type, AA005-02 type), the output voltage of the Wheatstone bridge circuit increases linearly with increasing external magnetic field. You can see that it is saturated.

9 is a diagram for explaining a GMR characteristic. As shown in FIG. 9, the GMR is a layered structure of ferromagnetic and nonmagnetic materials. The GMR is a spin valve structure in which ferromagnetic materials are arranged in different directions with ferromagnetic materials interposed therebetween.

Accordingly, when the external magnetic field is applied in the "horizontal" direction of the ferromagnetic material, the alignment direction of the ferromagnetic material is aligned in the same direction as the external magnetic field, and ultimately, the resistance value of the GMR becomes very low. On the other hand, when an external magnetic field is applied in the "vertical" direction of the ferromagnetic array, the resistance value of the GMR becomes very high.

As such, according to the characteristics of the GMR, as shown on the left side of FIG. 10, when the GMRs of the magnetic sensor 150 are disposed perpendicular to the magnetic field applied by the permanent magnets 131 and 132, the resistance of the GMR This is very high, the output change of the magnetic sensor 150 according to the change in the magnetic field does not occur.

However, as shown on the right side of FIG. 10, when the GMRs of the magnetic sensor 150 are arranged obliquely in the magnetic field applied by the permanent magnets 131 and 132, the resistance values of the GMRs change according to the magnetic field change. . This is due to the application of a horizontal component in addition to the vertical component of the magnetic field to the GMRs of the magnetic sensor 150.

The angle formed by the 'GMR of the magnetic sensor 150' and the 'magnetic field applied by the permanent magnets 131 and 132' may be determined from 0 ° to 90 °. As shown in FIG. 11, the strip 184 It is preferable to determine the linear output of the magnetic sensor 150 according to the change of the amount of magnetic material in the test region of.

Specifically, after the strip is removed from the magnetic field applying apparatus so that the strip 184 does not affect the magnetic sensor 150, that is, only the 'magnetic field by the permanent magnets 131 and 132' is applied to the magnetic sensor 150. When applied, it is more preferable to arrange the permanent magnets 131 and 132 at an angle such that the output of the magnetic sensor 150 is located at the center of the linear section.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but, on the contrary, It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention.

110: horizontal base plate 120: vertical base plate
131, 132, 133: fixed parts 141, 142: permanent magnet
150: magnetic sensor 161, 162: post
170: strip holder mount 180: strip holder
184: strip 185: test area

Claims (8)

Magnetic field applying unit; And
And a magnetic sensor for detecting a change in the magnetic field applied to the magnetic field applying unit by the magnetic material attached to the receptor that captures the target biomaterial.
And an angle between the magnetic field applied by the magnetic field applying unit and the magnetic sensor is adjustable.
The method of claim 1,
The magnetic sensor includes:
Maintaining a specific angle with the magnetic field applied by the magnetic field applying unit,
The specific angle is,
And a linear angle of the output of the magnetic sensor according to the change of the magnetic field.
The method of claim 2,
The specific angle is,
When there is no change in the magnetic field due to the magnetic material, the biological material analysis device, characterized in that the angle to the center of the linear section of the output of the magnetic sensor.
The method of claim 1,
A horizontal base plate, a vertical base plate, a plurality of fixing parts fixed to the vertical base plate, a plurality of posts fixed to the horizontal base plate, a strip holder mounting part fixed to the plurality of posts, and a strip holder. Biomaterial analysis device.
5. The method of claim 4,
The horizontal base plate is a means for supporting a vertical base plate, the vertical base plate is a biological material analysis device, characterized in that a plurality of fixing parts for fixing a plurality of permanent magnets and magnetic sensors are installed.
6. The method of claim 5,
Among the plurality of fixing parts, some of the permanent magnet is installed and fixed and the installation position is variable, the other fixed portion is a magnetic sensor is installed and the biomaterial analysis device, characterized in that the installation position is variable.
5. The method of claim 4,
The strip holder includes a body, a handle and a sample injector,
One side of the strip holder is a biomaterial analysis device, characterized in that one side is open so that the magnetic sensor and the strip can be in close contact without hitting the protruding magnetic sensor when the slide holder is fixed to the strip holder mounting.
The method of claim 1,
The magnetic sensor includes:
A Wheatstone bridge circuit comprising two reference resistors facing each other and two magnetic resistors facing each other; And
And a variable resistor connected in parallel to any one of the two reference resistors.
The voltage change between two opposite nodes of the Wheatstone bridge circuit is output as a magnetic field change detection result,
And the resistance value of the variable resistor is a resistance value for adjusting an unbalanced state of the Wheatstone bridge circuit by the magnetic field applied by the magnetic field applying unit to an equilibrium state.

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