Disclosure of Invention
The invention aims to solve the problems in the prior art and provides a biological magnetic bead detection device and method based on a magnetoelectric composite material sensor.
In order to achieve the purpose, the invention is realized by adopting the following technical scheme:
A biological magnetic bead detection device based on a magnetoelectric composite material sensor comprises a signal processing module, a detection silicon plate placing port, a packaging shell, a rotating bracket, a permanent magnet, a sensor and a conductive slip ring;
The signal processing module and the detection silicon plate placing port are arranged outside the packaging shell;
The rotary support and the motor are arranged in the packaging shell, the conductive slip ring, the permanent magnet and the sensor are arranged on the rotary support, the permanent magnets are symmetrically arranged on two sides of the sensor, and the sensor is arranged below the detection silicon plate placing opening;
The signal output end of the sensor is sequentially connected with the conductive slip ring and the signal processing module.
The invention further improves that:
the output end of the signal processing module is connected with a display;
the display is arranged at the top of the packaging shell, and the signal processing module is arranged in the display.
The rotating support comprises a conductive slip ring support and a sensor support;
the conductive slip ring support is connected with a motor, the motor drives the conductive slip ring support to rotate, and the sensor support is arranged on one side of the conductive slip ring support;
The conductive slip ring is arranged on the conductive slip ring support, and the permanent magnet and the sensor are arranged on the sensor support.
The signal output end of the sensor is sequentially connected with the conductive slip ring and the signal processing module through signal wires, and signal wire through holes are formed in the end face of the sensor support and the inside of the display.
The sensor includes two magnetostrictive layers at upper and lower ends and a piezoelectric layer disposed between the two magnetostrictive layers.
The length of the magnetostriction layer is 30mm, the width of the magnetostriction layer is 2.5mm, and the length of the piezoelectric layer is 12mm, and the width of the piezoelectric layer is 2.5mm.
The distance between the two permanent magnets was 70mm.
The permanent magnet is a neodymium-iron-boron permanent magnet.
The permanent magnet is of a cylindrical structure, the diameter of the permanent magnet is 12mm, and the height of the permanent magnet is 14mm.
A biological magnetic bead detection method based on a magnetoelectric composite material sensor comprises the following steps:
Placing a silicon plate to be detected, which is coupled with biomolecules and magnetic beads, on a detection silicon plate placing opening, rotating a rotating bracket, and magnetizing the magnetic beads on the silicon plate to be detected by a permanent magnet when a sensor rotates to the lower part of the detection silicon plate placing opening, so that a magnetic field of the sensor generates charge signals, and simultaneously, transmitting the generated charge signals to a signal processing module by the sensor through a conductive slip ring;
the signal processing module detects the charge signal and acquires a detection result.
Compared with the prior art, the invention has the following beneficial effects:
the invention discloses a biological magnetic bead detection device based on a magnetoelectric composite material sensor, wherein a signal processing module and a detection silicon plate placing port are arranged outside a packaging shell of the device, a rotating bracket is arranged inside the packaging shell, a sensor and a permanent magnet are arranged on the rotating bracket, the sensor and the detection silicon plate placing port are correspondingly arranged, the rotating bracket can drive the permanent magnet and the sensor to rotate, when the sensor rotates to the vicinity of the silicon plate placing port to be detected, the permanent magnet magnetizes magnetic beads on the silicon plate to be detected, the sensor further generates corresponding magnetic field changes and generates charge signals, and charge wire numbers of the sensor are conveyed to the signal processing module through a conductive slip ring, so that the detection of the biological magnetic beads is realized. The device disclosed by the invention converts a direct current magnetic field generated by the magnetic beads on the silicon plate to be detected into an alternating magnetic field by rotating the sensor, so that the detection limit and sensitivity of the sensor are improved, meanwhile, a permanent magnet is provided for replacing an excitation coil to provide a bias magnetic field, the space occupancy rate is reduced to a certain extent, meanwhile, the permanent magnet can work without an additional power supply, the heating phenomenon caused by long-time work is avoided, the measurement error caused by temperature is also reduced, the permanent magnet is matched with the sensor, and the device is used as a sensitive element of a weak magnetic field, and has high detection stability, good low-frequency response effect and high resolution.
Furthermore, the processing reality unit comprises a display and a signal processing module, and visual display of detection results is facilitated through the display.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments of the present invention. The components of the embodiments of the present invention generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations.
Thus, the following detailed description of the embodiments of the invention, as presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be noted that like reference numerals and letters refer to like items in the following figures, and thus once an item is defined in one figure, no further definition or explanation thereof is necessary in the following figures.
In the description of the embodiments of the present invention, it should be noted that, if the terms "upper," "lower," "horizontal," "inner," and the like indicate an azimuth or a positional relationship based on the azimuth or the positional relationship shown in the drawings, or the azimuth or the positional relationship in which the inventive product is conventionally put in use, it is merely for convenience of describing the present invention and simplifying the description, and does not indicate or imply that the apparatus or element to be referred to must have a specific azimuth, be configured and operated in a specific azimuth, and thus should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and the like, are used merely to distinguish between descriptions and should not be construed as indicating or implying relative importance.
Furthermore, the term "horizontal" if present does not mean that the component is required to be absolutely horizontal, but may be slightly inclined. As "horizontal" merely means that its direction is more horizontal than "vertical", and does not mean that the structure must be perfectly horizontal, but may be slightly inclined.
In the description of the embodiments of the present invention, it should also be noted that, unless explicitly stated or limited otherwise, the terms "disposed," "mounted," "connected," and "connected" should be interpreted broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected, mechanically connected, electrically connected, directly connected, indirectly connected through an intermediate medium, or communicating between two elements. The specific meaning of the above terms in the present invention can be understood by those of ordinary skill in the art according to the specific circumstances.
The invention is described in further detail below with reference to the attached drawing figures:
Referring to fig. 1-4, an embodiment of the invention discloses a biological magnetic bead detection device based on a magnetoelectric composite material sensor, wherein a layered magnetoelectric composite material sensor and a permanent magnet generating a bias magnetic field are arranged on a bracket and driven by a motor to rotate at a certain frequency, and a certain position above a magnetic bead fixed sensor of a biological sample to be detected is coupled. When the sensor rotates to the lower part of the magnetic beads, the magnetic beads are magnetized by the rotating permanent magnets, so that a magnetic field signal with the same frequency of motor rotation is generated, and the signal is sensed by the sensor, so that the detection of the biological magnetic beads is realized.
The embodiment of the invention comprises a display 1, a detection silicon plate placing port 2, a packaging shell 3, a signal processing module 4, a rotary support 5, a permanent magnet 6, a sensor 7, a motor 8, a signal wire through hole 9, a threaded hole 10, a conductive slip ring support 11, a sensor support 12, a magnetostrictive layer 13, epoxy resin 14, a piezoelectric layer 15 and a conductive slip ring 16.
The device disclosed by the invention is provided with the display 1 at the top of the packaging shell 3, one side of the display is provided with the detection silicon plate placing port 2 for placing the silicon plate to be detected, a user can finish the coupling of the biomolecules to be detected and the magnetic beads on the silicon plate by adopting a sandwich immunization method, and the silicon plate coupled with the biomolecules and the magnetic beads is placed at the detection silicon plate placing port 2 of the device for detection as a sample to be detected of the device.
The display 1 is internally provided with a signal processing module 4, the packaging shell 3 is internally provided with a conductive slip ring support 11, the conductive slip ring support 11 is provided with a threaded hole 10, the conductive slip ring support 11 is rotationally connected with a motor 8 through the threaded hole 10, one side of the conductive slip ring support 11 is connected with a sensor support 12, the upper end of the conductive slip ring support 11 is provided with a conductive slip ring 16, the conductive slip ring 16 is fixedly connected with the conductive slip ring support 11 through bolts, the input end of the conductive slip ring 16 rotates along with the rotating support 5, and the output end is static relative to the shell of the device, so that the wiring problem of the rotating sensor 7 and the static signal processing module 4 is solved.
Be provided with sensor 7 on the sensor support 12, the both sides of sensor 7 all are provided with permanent magnet 6, according to actual demand, can adjust the distance between two permanent magnets 6, adjust the size of bias magnetic field, and sensor 7 corresponds with detecting the silicon board and place mouth 2.
A plurality of signal wire through holes 9 are formed in the sensor support 12, the bottom of the display 1 is also provided with the signal wire through holes 9, the signal output end of the sensor 7 is connected with the input end of the conductive slip ring 16 through a signal outgoing line, and the output end of the conductive slip ring 16 is connected with the input end of the signal processing module 4 through a signal outgoing line. The signal line through holes 9 are arranged according to the line opening of the signal outgoing line.
The signal processing module 4 in the embodiment of the invention is connected with the output end of the conductive slip ring 16 through leading out an SMA interface, the weak electric charge quantity output by the sensor 7 is amplified, then a certain filtering process is carried out, and the signal processing module 4 is displayed for a user, the signal processing module 4 comprises a charge amplifier, a low-pass filter and a detection unit, the input end of the charge amplifier is connected with the output end of the sensor 7 through the conductive slip ring 16, so as to amplify the weak signal output by the sensor, the output end of the charge amplifier is connected with the low-pass filter, and the low-pass filter is used for filtering the power frequency interference of 50 Hz. The other end of the low-pass filter is connected with a display 1 for displaying information of the number of the magnetic beads marked with the biological sample to be detected. The charge amplifier amplifies the signal output by the sensor 7, then filters the signal through the low-pass filter to generate a voltage signal, finally detects the voltage signal through the detection unit to obtain the number of magnetic beads or concentration information of biomolecules, and finally displays the information through the display 1.
Referring to fig. 5, the sensor 7 disclosed in the embodiment of the present invention includes a magnetostrictive layer 13 and a piezoelectric layer 15, where the piezoelectric layer 15 is provided with an upper layer and a lower layer, and after the piezoelectric layer 15 is polarized in the thickness direction, the upper and lower surfaces are coated with conductive silver paste and are adhered with finger electrodes, and the piezoelectric layer 15 and the magnetostrictive layer 13 are adhered together by epoxy resin 14. Wherein, the length of magnetostriction layer 13 is 30mm, and wide 2.5mm, magnetostriction layer 13 is formed by bonding 4 layers of Metglas through epoxy resin 14, and piezoelectric layer 15 is formed by PZT piezoceramics cutting, and the length of piezoelectric layer 15 is 12mm, wide 2.5mm, thickness 0.6mm. Wherein Metglas is used as a magnetostrictive material, strain is generated after a magnetic field is induced, and corresponding electric charge is generated after the strain is transferred to the piezoelectric ceramic PZT, and the quantity of the electric charge also indicates the magnitude of the induced magnetic field. According to the non-linear response of Metglas to magnetic field, it has a point that is most sensitive to magnetic field variation, the magnitude of which is its optimal bias magnetic field. Magneto-electric composite sensors are therefore typically intended to operate in a certain dc bias magnetic field. Wherein the magnetoelectric composite sensor operates in an L-T mode, that is, the sensitive direction of the magnetostrictive material layer is along the length direction, and the piezoelectric layer is polarized along the thickness direction.
The permanent magnets 6 disclosed by the embodiment of the invention are neodymium iron boron permanent magnets, the permanent magnets 6 are of circular structures, the diameter is 12mm, the thickness is 14mm, the distance between the two permanent magnets 6 is 70mm, and the optimal bias magnetic field can be provided for the sensor 7. The present invention uses the permanent magnet 6 instead of the conventional exciting coil to provide the bias magnetic field, achieves the reduction of the volume, and can operate without an additional power supply. The permanent magnet 6 is used for replacing the traditional energizing coil to provide the bias magnetic field of the sensor, so the sensor belongs to a passive device, does not have a heating phenomenon working for a long time, and does not have measurement deviation caused by temperature.
The embodiment of the invention discloses a biological magnetic bead detection method based on a magnetoelectric composite material sensor,
After the device is started, the motor 8 rotates (5 Hz) at a fixed speed of 300r/min, when the sensor bracket 12 rotates to the vicinity of the lower part of the magnetic bead each time, the permanent magnet 6 on the sensor bracket 12 magnetizes the magnetic bead, the magnetic field around the sensor 7 working at the optimal bias magnetic field can change slightly, the magnetostrictive layer 13 of the sensor 7 generates deformation with the same frequency as the rotation of the motor 8 along the length direction, the deformation is transmitted to the middle piezoelectric layer 15, the piezoelectric layer 15 generates electric polarization along the thickness direction due to the piezoelectric effect, so that a charge signal with the same frequency as the rotation is generated along the thickness direction, the magnetic field generated by the magnetic bead can be converted into the charge signal, the charge signal is transmitted to the signal processing module 4 through the signal outgoing line, the charge signal is primarily processed through the charge amplifier and the low-pass filter, the voltage signal is generated, finally the detection result is obtained, and the detection result is displayed through the display 1.
In the embodiment of the invention, the magnetic beads are prepared by taking a silicon plate as a carrier, carrying out chemical modification and modification of a capture antibody on the surface of the silicon plate by using a sandwich immunization method, completing the specific combination of molecules to be detected, the capture antibody and a labeled antibody, completing the specific combination of the magnetic beads and the labeled antibody, thereby realizing the coupling of biomolecules and the magnetic beads and fixing the biomolecules and the magnetic beads on the silicon plate.
The embodiment of the invention utilizes the sensitivity of the magnetoelectric composite material sensor to an alternating magnetic field. The direct-current magnetic field of the magnetic beads is converted into an alternating magnetic field in a rotating manner, so that the detection limit and sensitivity of the sensor 7 to the magnetic beads can be improved. Since the centrifugal force is too high due to too high a rotation speed of the motor 8, the rotation frequency of the motor 8 is controlled to be about 5Hz in actual operation, and the low frequency characteristic of the magnetoelectric composite sensor is utilized. One example of the present invention is the use of a four-order chebyshev low-pass filter with a cut-off frequency of 15 Hz. The other end of the low-pass filter is connected with a display 1 for displaying the detected information of the number of the magnetic beads marked with the biological sample to be detected.
According to the embodiment of the invention, the magnetoelectric composite sensor is used as a sensitive element of a weak magnetic field, so that the stability is good, the low-frequency response is good, and the resolution is high. The device is convenient to use, only needs to be fixed with the silicon plate of biological magnetic beads and put into the corresponding detection port of device can, and contactless detection has reduced the influence to sensor 7 surface quality, has guaranteed the accuracy of detection, and the sensor does not need to change as the inside factor of device, can repetitious usage, and is with low costs.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.