SE1830335A1 - System and method for gene detection - Google Patents

System and method for gene detection

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Publication number
SE1830335A1
SE1830335A1 SE1830335A SE1830335A SE1830335A1 SE 1830335 A1 SE1830335 A1 SE 1830335A1 SE 1830335 A SE1830335 A SE 1830335A SE 1830335 A SE1830335 A SE 1830335A SE 1830335 A1 SE1830335 A1 SE 1830335A1
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SE
Sweden
Prior art keywords
magnetic sensors
magnetic
output port
resistor
positive
Prior art date
Application number
SE1830335A
Other languages
Swedish (sv)
Other versions
SE543509C2 (en
Inventor
Lanfang Xian
Original Assignee
Xianlan Tech Co Limited
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Publication date
Application filed by Xianlan Tech Co Limited filed Critical Xianlan Tech Co Limited
Priority to SE1830335A priority Critical patent/SE543509C2/en
Publication of SE1830335A1 publication Critical patent/SE1830335A1/en
Publication of SE543509C2 publication Critical patent/SE543509C2/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6816—Hybridisation assays characterised by the detection means
    • C12Q1/6825—Nucleic acid detection involving sensors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6816—Hybridisation assays characterised by the detection means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means

Abstract

A system for gene detection includes a sensor module including a plurality of magnetic sensors in an arrangement of a matrix and a signal processing chip including a front-end circuit and a signal processing circuit. The sensor module is formed on the signal processing chip through sputtering. The signal processing chip is configured to transform variation of the reluctivity of the magnetic sensors into a first electrical signal, process the first electrical signal and output a second electrical signal representing a detection result of a DNA molecule to be detected. The frontend circuit includes a row address selector, a column address selector, a preamplifier and a biasing circuit. The magnetic sensors are chemically pretreated and combined with a biological probe. The combined magnetic sensors and biological probe are in sufficient contact with combined magnetic particles and DNA molecules to be detected.

Description

SYSTEM AND METHOD FOR GENE DETECTION Field of the Patent Application The present patent application generally relates to medical electronics and more specifically to a system and a method for gene detection.
Background Gene or molecular biology detection is important to early diagnosis of diseases.Conventional gene detection depends on optical means Which may lead to opticallosses such as reflection and refraction, and therefore the resolution of the detectionis relatively low and the detection is expensive and needs to be operated byprofessional staff. ln recent years, gene detection systems based on magnetic labelshave been proposed and such systems are more stable, faster and easier to operatecompared With conventional gene detection systems. However, sensitivity, power consumption and yield are still the main bottlenecks of these systems.
Summary The present patent application is directed to a system and method for gene detection.ln one aspect, the system for gene detection includes a sensor module including aplurality of magnetic sensors in an arrangement of a matrix; and a signal processingchip configured to transforrn variation of the reluctivity of the magnetic sensors intoa first electrical signal, process the first electrical signal and output a secondelectrical signal representing a detection result of a DNA molecule to be detected.
The plurality of magnetic sensors are chemically pretreated and combined With a 1 biological probe. The combined magnetic sensors and biological probe are disposedin a DC magnetic field and an AC magnetic field, and in sufficient contact Withcombined magnetic particles and DNA molecules to be detected, so that the DNAmolecules to be detected are matched and hybridized With the biological probe. Theplurality of magnetic sensors are then cleaned so that the DNA molecules to bedetected that are not hybridized are removed; and the magnetic particles combinedWith the DNA molecules to be detected that are hybridized are relatively fixedabove the magnetic sensors so that a scattered magnetic field is formed and the reluctivity of the magnetic sensors varies under the scattered magnetic field.
The sensor module may be formed on the signal processing chip through sputtering.The signal processing chip may include a front-end circuit configured to transforrnvariation of the reluctivity of the magnetic sensors into a first electrical signal and asignal processing circuit configured to process the first electrical signal and output asecond electrical signal representing a detection result of a DNA molecule to be detected.
The front-end circuit may include a row address selector and a column addressselector coordinated With each other and configured to allow the current to floW into selected magnetic sensors.
The front-end circuit may further include a pre-amplifier configured to amplify theelectrical signal representing variation of the reluctivity of the magnetic sensors soas to produce the first electrical signal, and the pre-amplifier comprises a differentialamplifier, a first clipper stabilizing circuit, a second clipper stabilizing circuit, athird clipper stabilizing circuit, a first resistor and a second resistor; the differentialamplifier comprises a positive input port, a negative input port, a first positiveoutput port, a first negative output port, a second positive output port and a second negative output port; the first clipper stabilizing circuit is connected With the first 2 positive output port and the first negative output port; the second clipper stabilizingcircuit is connected With the second positive output port and the second negativeoutput port; the third clipper stabilizing circuit is connected With the positive inputport and the negative input port; the positive input port is connected With the firstnegative output port through the first resistor; the negative input port is connectedWith the second negative output port through the second resistor; the input signal ofthe differential amplifier is an electrical signal output from the magnetic sensors andrepresenting variation of the reluctivity of the magnetic sensors, and input throughthe positive input port and the negative input port; the output signals of thedifferential amplifier comprise a first output signal output from the first positive output port and a second output signal output from the second positive output port.
The pre-amplifier may further include a third resistor, a fourth resistor, a firstcapacitor and a second capacitor; the positive input port is connected With theground through the third resistor and the first capacitor; the second negative outputport is connected With the ground through the fourth resistor and the second capacitor.
The front-end circuit may further include a biasing circuit; the biasing circuitcomprises a plurality of diodes individually corresponding to the plurality ofmagnetic sensors; each diode is connected in series With a corresponding magnetic sensor so as to prevent the current from floWing into unselected magnetic sensors.
In another aspect, the present patent application provides a system for genedetection. The system for gene detection includes a sensor module including aplurality of magnetic sensors in an arrangement of a matrix; and a signal processingchip. The plurality of magnetic sensors are chemically pretreated and combined Witha biological probe. The combined magnetic sensors and biological probe are disposed in a DC magnetic field and an AC magnetic field, and in sufficient contact 3 With combined magnetic particles and DNA molecules to be detected, so that the DNA molecules to be detected are matched and hybridized With the biological probe.
The plurality of magnetic sensors are then cleaned so that the DNA molecules to bedetected that are not hybridized are removed. The magnetic particles combined Withthe DNA molecules to be detected that are hybridized are relatively fixed above themagnetic sensors so that a scattered magnetic field is forrned and the reluctivity ofthe magnetic sensors varies under the scattered magnetic field. The sensor module isforrned on the signal processing chip through sputtering. The signal processing chipincludes a front-end circuit configured to transforrn variation of the reluctivity of themagnetic sensors into a first electrical signal and a signal processing circuitconfigured to process the first electrical signal and output a second electrical signalrepresenting a detection result of a DNA molecule to be detected. The front-endcircuit includes a row address selector and a column address selector coordinatedWith each other and configured to allow the current to floW into selected magneticsensors, and a biasing circuit and a pre-amplifier. The biasing circuit includes aplurality of diodes individually corresponding to the plurality of magnetic sensors;each diode is connected in series With a corresponding magnetic sensor so as toprevent the current from floWing into unselected magnetic sensors. The pre-amplifier includes a differential amplifier, a first clipper stabilizing circuit, a secondclipper stabilizing circuit, a third clipper stabilizing circuit, a first resistor and asecond resistor; the differential amplifier includes a positive input port, a negativeinput port, a first positive output port, a first negative output port, a second positiveoutput port and a second negative output port. The first clipper stabilizing circuit isconnected With the first positive output port and the first negative output port. Thesecond clipper stabilizing circuit is connected With the second positive output portand the second negative output port. The third clipper stabilizing circuit is connectedWith the positive input port and the negative input port. The positive input port isconnected With the first negative output port through the first resistor. The negative input port is connected With the second negative output port through the second 4 resistor. The input signal of the differential amplifier is an electrical signal outputfrom the plurality of magnetic sensors and representing variation of the reluctivityof the magnetic sensors, and input through the positive input port and the negativeinput port; and the output signals of the differential amplifier include a first outputsignal output from the first positive output port and a second output signal output from the second positive output port.
The pre-amplifier may further include a third resistor, a fourth resistor, a firstcapacitor and a second capacitor; the positive input port is connected to the groundthrough the third resistor and the first capacitor; the second negative output port is connected With the ground through the fourth resistor and the second capacitor.
In yet another aspect, the present patent application provides a method for genedetection. The method for gene detection includes step 1: magnetizing a plurality ofmagnetic particles With a DC magnetic field and an AC magnetic field; step 2:combining a plurality of magnetized magnetic particles and a plurality of DNAmolecules to be detected; step 3: chemically pretreating magnetic sensors andcombining the magnetic sensors With a biological probe; step 4: establishing the DCmagnetic field and the AC magnetic field around the combined magnetic sensorsand biological probe as described in step 3 and establishing a signal baseline; step 5:disposing the combined DNA molecules to be detected and magnetic particles asdescribed in step 2 on the combined magnetic sensors and biological probe asdescribed in step 3 so that the combined DNA molecules to be detected andmagnetic particles are in sufficient contact With the combined magnetic sensors andbiological probe; step 6: cleaning the plurality of magnetic sensors, removing theDNA molecules to be detected that are not hybridized, and then relatively fixing themagnetic particles combined With the hybridized DNA molecules to be detectedabove the magnetic sensors so that a scattered magnetic field can be formed; step 7:transforrning variation of the reluctivity of the plurality of magnetic sensors into a first electrical signal through a signal processing chip, the reluctivity of the plurality5 of magnetic sensors Varying under the scattered magnetic field; and step 8:processing the first electrical signal and outputting a second electrical signalrepresenting a detection result of the DNA molecules to be detected With the signal processing chip.
Brief Description of the Drawings FIG. l is a block diagram of a system for gene detection in accordance With an embodiment of the present patent application.
FIG. 2 illustrates the structure of a magnetic sensor matrix of the system for gene detection as depicted in FIG. 1.
FIG. 3 illustrates the structure of a magnetic sensor of the magnetic sensor matrix as depicted in FIG. 2.
FIG. 4 is a block diagram of a signal processing chip of the system for gene detection as depicted in FIG. 1.
FIG. 5 is a schematic circuit diagram of a front-end circuit of the system for gene detection as depicted in FIG. 1.
FIG. 6 is a schematic circuit diagram of a pre-amplifier of the system for gene detection as depicted in FIG. 1.
FIG. 7 is a floWchart illustrating a method for gene detection executed by the systemas depicted in FIG. 1.
Detailed Description Reference will now be made in detail to a preferred embodiment of the system andmethod for gene detection disclosed in the present patent application, examples ofwhich are also provided in the following description. Exemplary embodiments ofthe system and method for gene detection disclosed in the present patent applicationare described in detail, although it will be apparent to those skilled in the relevant artthat some features that are not particularly important to an understanding of the system and method for gene detection may not be shown for the sake of clarity.
Furthermore, it should be understood that the system and method for gene detectiondisclosed in the present patent application is not limited to the precise embodimentsdescribed below and that Various changes and modifications thereof may be effectedby one skilled in the art without departing from the spirit or scope of the protection.For example, elements and/ or features of different illustratiVe embodiments may becombined with each other and/or substituted for each other within the scope of this disclosure.
FIG. 1 is a block diagram of a system for gene detection in accordance with anembodiment of the present patent application. Referring to FIG. 1, the system for gene detection 100 includes a sensor module 101 and a signal processing chip 103.
Referring to FIG. 2 and FIG. 3, the sensor module 101 is formed on the signalprocessing chip 103 through sputtering and the sensor module 101 includes amagnetic sensor matrix 407. The magnetic sensor matrix 407 includes a number ofmagnetic sensors 408 in an arrangement of a matrix. Each magnetic sensor 408 isformed by stacking layers of magnetic materials 408a, and the reluctiVity of eachmagnetic sensor Varies with the spin alignment of the electrons of two layers of magnetic materials 408a. When disposed in an extemal magnetic field, the 7 reluctivity of the stacked magnetic materials 408a varies with the intensity of the external magnetic field.
The multiple magnetic sensors 408 are chemically pretreated, so that the multiplemagnetic sensors 408 are combined with a biological probe (not shown in thefigures). The combined magnetic sensors 408 and biological probe are disposed in aDC magnetic field and an AC magnetic field and in sufficient contact with thecombined multiple magnetic particles and DNA molecules to be detected, so that the DNA molecules to be detected are matched and hybridized with the biological probe.
The multiple magnetic sensors 408 are then cleaned, and the DNA molecules to bedetected that are not hybridized are removed. The magnetic particles combined withthe DNA molecules that are hybridized are relatively fixed above the magneticsensors 408, so that a scattered magnetic field can be formed. The reluctivity of the multiple magnetic sensors 408 varies under the scattered magnetic field.
Referring to FIG. 4, the signal processing chip 103 includes a front-end circuit 201and a signal processing circuit 203. The front-end circuit 201 is configured totransforrn variation of the reluctivity of the multiple magnetic sensors 408 in thesensor module 101 into a first electrical signal (e.g. a voltage signal Vin). The signalprocessing circuit 203 is configured to process the electrical signal and output asecond electrical signal representing a detection result of the DNA molecules to be detected (e. g. a voltage signal Vout).
Referring to FIG. 5, the front-end circuit 201 includes a row address selector 403, a column address selector 405, a biasing circuit 401 and a pre-amplifier 409.
The row address selector 403 includes multiple row switches and the columnaddress selector 405 includes multiple column switches. The multiple row switches and the multiple column switches are coordinated with each other, connected with 8 an external power supply VDD, and configured to allow the current to flow into selected magnetic sensors 408.
The biasing circuit 401 includes multiple diodes. The multiple diodes areindividually corresponding to the multiple magnetic sensors 408 and each diode isconnected in series with a corresponding magnetic sensor 408 so as to prevent thecurrent from flowing into unselected magnetic sensors 408. The configuration of themultiple diodes helps to improve the accuracy of the system for gene detection 100 and reduce power consumption.
Because one magnetic sensor 408 is selected at a time, all magnetic sensors 408 canshare the same biasing circuit 401 and the same pre-amplifier 409, which reducespower consumption and system noise. At the same time, the noise of the magneticsensors 408 is at the same order of magnitude as the smallest detection signal andthe noise of the magnetic sensors 408 is deterrnined by its own material andstructure, and therefore the noise of the front-end circuit 201 is lower than that of the magnetic sensors 408.
Referring to FIG. 6, the pre-amplifier 409 is configured to amplify the electricalsignal representing variation of the reluctivity of the magnetic sensors 408 so as toproduce the first electrical signal and the pre-amplifier 409 includes a differentialamplifier 501, a first clipper stabilizing circuit 503, a second clipper stabilizingcircuit 505, a third clipper stabilizing circuit 507, a first resistor 509, a secondresistor 511, a third resistor 510, a fourth resistor 512, a first capacitor 513 and a second capacitor 515.
The differential amplifier 501 includes a positive input port, a negative input port, afirst positive output port, a first negative output port, a second positive output port, and a second negative output port.
The input signal Vin of the differential amplifier 501 is an electrical signal (e.g. ACsignal) output from the multiple magnetic sensors 408, representing variation of thereluctivity of the multiple magnetic sensors 408, and input into the differentialamplifier 501 through the positive input port and the negative input port. The outputsignal Vs of the differential amplifier 501 includes a first output signal Va and asecond output signal Vb. The first output signal Va is output from the first positiveoutput port. The second output signal Vb is output from the second positive outputport. In this embodiment, the first output signal Va is an AC signal and the secondoutput signal Vb is a DC signal.
The first clipper stabilizing circuit 503 is connected With the first positive outputport and the first negative output port. The second clipper stabilizing circuit 505 isconnected With the second positive output port and the second negative output port.The third clipper stabilizing circuit 507 is connected With the positive input port andthe negative input port.
The positive input port is connected With the first negative output port through thefirst resistor 509. The negative input port is connected With the second negativeoutput port through the second resistor 511. In addition, the positive input port isconnected to the ground through the third resistor 510 and the first capacitor 513and the second negative output port is connected to the ground through the fourthresistor 512 and the second capacitor 515 so as to filter stray Waves and loWer the noise of the output signal Vs.
The utilization of the first clipper stabilizing circuit 503, the second clipperstabilizing circuit 505 and the third clipper stabilizing circuit 507 loWers 1/f noise.The first capacitor 513 and the second capacitor 515 have effectively prevented DC current from floWing into a feedback loop and reduced the requirement for the drive capability of the output port. The input impedance of the pre-amplifier 409 is Very high, so the input current is Very small, Which further suppress the l/f noise. The pre-amplifier 409 realizes AC coupling and DC coupling While remaining low noise.
FIG. 7 is a floWchart illustrating a method for gene detection executed by the systemas depicted in FIG. 1. The method includes the following steps: Step 601: magnetizing multiple magnetic particles With a DC magnetic field and anAC magnetic field; the DC magnetic field and the AC magnetic field can beestablished through an electrified coil; Step 603: combining DNA molecules to be detected With the multiple magnetic particles Which are magnetized; Step 605: chemically pretreating magnetic sensors, so that the magnetic sensors are combined With a biological probe; Step 607: establishing the DC magnetic field and the AC magnetic field around thecombined magnetic sensors and biological probe as described in the step 605, and establishing a signal baseline; Step 609: disposing the combined DNA molecules and magnetic particles asdescribed in the step 603 on the combined magnetic sensors and biological probe as described in the step 605 for sufficient contact;Step 6l l: cleaning the magnetic sensors first and remoVing the DNA molecules to be detected that are not hybridized since the direct match of the DNA molecules to be detected and the biological probe Will cause hybridization, and then relatively 11 fixing the magnetic particles combined with the hybridized DNA molecules to be detected above the magnetic sensors so that a scattered magnetic field is formed; Step 613: transforrning variation of the reluctivity of the magnetic sensors into afirst electrical signal with the front-end circuit 201, the reluctivity of the magnetic sensors varying under the scattered magnetic field; and Step 615: processing the first electrical signal and outputting a second electricalsignal representing a detection result of a DNA molecule to be detected with the signal processing circuit 203.
Compared with the conventional systems and methods for gene detection, thesystem and the method provided by the present patent application have thefollowing advantages. (1) The signal processing chip 103 is formed on the sensormodule 101 through sputtering, which contributes to good yield, high sensitivity,low parasitic capacitance, good scalability, smaller size of the system and strongeranti-interference capability (especially the capability of resisting electromagneticinterference). (2) All magnetic sensors share a biasing circuit and a pre-amplifierand clipper stabilizing circuits are used, which leads to high input impedance, smallinput current, and further suppressed 1/f noise, so that the noise of the signalprocessing chip 103 is lower than that of the sensor module and the sensitivity of thegene detection is improved. (3) Because all magnetic sensors share a biasing circuitand a pre-amplifier and the biasing circuit includes multiple diodes, the powerconsumption of the system for gene detection gets to be optimized. (4)Because the structure of the system for gene detection is simple, the production yield is high.
While the present patent application has been shown and described with particular references to a number of embodiments thereof, it should be noted that various 12 other changes or modifications may be made Without departing from the scope of the present invention. 13

Claims (10)

What is claimed is:
1. A system for gene detection comprising: a sensor module comprising a plurality of magnetic sensors in an arrangement of amatrix; and a signal processing chip configured to transforrn Variation of the reluctivity of themagnetic sensors into a first electrical signal, process the first electrical signal andoutput a second electrical signal representing a detection result of a DNA moleculeto be detected; Wherein: the plurality of magnetic sensors are chemically pretreated and combined With abiological probe; the combined magnetic sensors and biological probe are disposed in a DC magneticfield and an AC magnetic field, and in sufficient contact With combined magneticparticles and DNA molecules to be detected, so that the DNA molecules to bedetected are matched and hybridized With the biological probe; the plurality of magnetic sensors are then cleaned so that the DNA molecules to bedetected that are not hybridized are removed; and the magnetic particles combined With the DNA molecules to be detected that arehybridized are relatively fixed above the magnetic sensors so that a scatteredmagnetic field is formed and the reluctivity of the magnetic sensors varies under the scattered magnetic field.
2. The system for gene detection of claim l, Wherein the sensor module is formed on the signal processing chip through sputtering.
3. The system for gene detection of claim l, Wherein the signal processing chip comprises a front-end circuit configured to transforrn variation of the reluctivity of the magnetic sensors into a first electrical signal and a signal processing circuit 14 configured to process the first electrical signal and output a second electrical signal representing a detection result of a DNA molecule to be detected.
4. The system for gene detection of claim 3, Wherein the front-end circuit comprisesa row address selector and a column address selector coordinated With each other and configured to allow the current to floW into selected magnetic sensors.
5. The system for gene detection of claim 4, Wherein the front-end circuit furthercomprises a pre-amplifier configured to amplify the electrical signal representingvariation of the reluctivity of the magnetic sensors so as to produce the firstelectrical signal, and the pre-amplifier comprises a differential amplifier, a firstclipper stabilizing circuit, a second clipper stabilizing circuit, a third clipperstabilizing circuit, a first resistor and a second resistor; the differential amplifiercomprises a positive input port, a negative input port, a first positive output port, afirst negative output port, a second positive output port and a second negative outputport; the first clipper stabilizing circuit is connected With the first positive outputport and the first negative output port; the second clipper stabilizing circuit isconnected With the second positive output port and the second negative output port;the third clipper stabilizing circuit is connected With the positive input port and thenegative input port; the positive input port is connected With the first negative outputport through the first resistor; the negative input port is connected With the secondnegative output port through the second resistor; the input signal of the differentialamplifier is an electrical signal output from the magnetic sensors and representingvariation of the reluctivity of the magnetic sensors, and input through the positiveinput port and the negative input port; the output signals of the differential amplifiercomprise a first output signal output from the first positive output port and a second output signal output from the second positive output port.
6. The system for gene detection of claim 5, Wherein the pre-amplifier furthercomprises a third resistor, a fourth resistor, a first capacitor and a second capacitor;the positive input port is connected With the ground through the third resistor andthe first capacitor; the second negative output port is connected With the ground through the fourth resistor and the second capacitor.
7. The system for gene detection of claim 4, Wherein the front-end circuit furthercomprises a biasing circuit; the biasing circuit comprises a plurality of diodesindividually corresponding to the plurality of magnetic sensors; each diode isconnected in series With a corresponding magnetic sensor so as to prevent the current from floWing into unselected magnetic sensors.
8. A system for gene detection comprising: a sensor module comprising a plurality of magnetic sensors in an arrangement of amatrix; and a signal processing chip; Wherein: the plurality of magnetic sensors are chemically pretreated and combined With abiological probe; the combined magnetic sensors and biological probe are disposed in a DC magneticfield and an AC magnetic field, and in sufficient contact With combined magneticparticles and DNA molecules to be detected, so that the DNA molecules to bedetected are matched and hybridized With the biological probe; the plurality of magnetic sensors are then cleaned so that the DNA molecules to bedetected that are not hybridized are removed; the magnetic particles combined With the DNA molecules to be detected that arehybridized are relatively fixed above the magnetic sensors so that a scatteredmagnetic field is formed and the reluctivity of the magnetic sensors varies under thescattered magnetic field; the sensor module is formed on the signal processing chip through sputtering; 16 the signal processing chip cornprises a front-end Circuit configured to transforrnvariation of the reluctivity of the rnagnetic sensors into a first electrical signal and asignal processing circuit configured to process the first electrical signal and output asecond electrical signal representing a detection result of a DNA rnolecule to bedetected; the front-end circuit comprises a row address selector and a column address selectorcoordinated With each other and configured to allow the current to floW into selectedrnagnetic sensors, and a biasing circuit and a pre-arnplifier; the biasing circuit cornprises a plurality of diodes individually corresponding to theplurality of magnetic sensors; each diode is connected in series With a correspondingrnagnetic sensor so as to prevent the current frorn floWing into unselected rnagneticsensors; the pre-arnplifier cornprises a differential arnplifier, a first clipper stabilizing circuit,a second clipper stabilizing circuit, a third clipper stabilizing circuit, a first resistorand a second resistor; the differential amplifier comprises a positive input port, anegative input port, a first positive output port, a first negative output port, a secondpositive output port and a second negative output port; the first clipper stabilizing circuit is connected With the first positive output port andthe first negative output port; the second clipper stabilizing circuit is connected With the second positive outputport and the second negative output port; the third clipper stabilizing circuit is connected With the positive input port and thenegative input port; the positive input port is connected With the first negative output port through thefirst resistor; the negative input port is connected With the second negative output port through thesecond resistor; the input signal of the differential arnplifier is an electrical signal output from the plurality of magnetic sensors and representing variation of the reluctivity of the 17 magnetic sensors, and input through the positive input port and the negative inputport; and the output signals of the differential amplifier comprise a first output signal outputfrom the first positive output port and a second output signal output from the second positive output port.
9. The system for gene detection of claim 8, Wherein the pre-amplifier furthercomprises a third resistor, a fourth resistor, a first capacitor and a second capacitor;the positive input port is connected to the ground through the third resistor and thefirst capacitor; the second negative output port is connected With the ground through the fourth resistor and the second capacitor.
10. A method for gene detection comprising: step l: magnetizing a plurality of magnetic particles With a DC magnetic field andan AC magnetic field; step 2: combining a plurality of magnetized magnetic particles and a plurality ofDNA molecules to be detected; step 3: chemically pretreating magnetic sensors and combining the magnetic sensorsWith a biological probe; step 4: establishing the DC magnetic field and the AC magnetic field around thecombined magnetic sensors and biological probe as described in step 3 andestablishing a signal baseline; step 5: disposing the combined DNA molecules to be detected and magneticparticles as described in step 2 on the combined magnetic sensors and biologicalprobe as described in step 3 so that the combined DNA molecules to be detected andmagnetic particles are in sufficient contact With the combined magnetic sensors andbiological probe; step 6: cleaning the plurality of magnetic sensors, removing the DNA molecules to be detected that are not hybridized, and then relatively fixing the magnetic particles 18 combined With the hybridized DNA molecules to be detected above the magneticsensors so that a scattered magnetic field can be formed; step 7: transforrning Variation of the reluctivity of the plurality of rnagnetic sensorsinto a first electrical signal through a signal processing chip, the reluctivity of theplurality of rnagnetic sensors Varying under the scattered rnagnetic field; and step 8: processing the first electrical signal and outputting a second electrical signalrepresenting a detection result of the DNA molecules to be detected With the signal processing chip. 19
SE1830335A 2018-11-15 2018-11-15 System and method for gene detection SE543509C2 (en)

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US5776672A (en) * 1990-09-28 1998-07-07 Kabushiki Kaisha Toshiba Gene detection method

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