SE2130016A1 - Method for gene detection - Google Patents

Method for gene detection

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Publication number
SE2130016A1
SE2130016A1 SE2130016A SE2130016A SE2130016A1 SE 2130016 A1 SE2130016 A1 SE 2130016A1 SE 2130016 A SE2130016 A SE 2130016A SE 2130016 A SE2130016 A SE 2130016A SE 2130016 A1 SE2130016 A1 SE 2130016A1
Authority
SE
Sweden
Prior art keywords
magnetic sensors
magnetic
resistor
output port
positive
Prior art date
Application number
SE2130016A
Other languages
Swedish (sv)
Inventor
Lanfang Xian
Original Assignee
Shenzhen Dansha Tech Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shenzhen Dansha Tech Co Ltd filed Critical Shenzhen Dansha Tech Co Ltd
Priority to SE2130016A priority Critical patent/SE2130016A1/en
Publication of SE2130016A1 publication Critical patent/SE2130016A1/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6816Hybridisation assays characterised by the detection means
    • C12Q1/6825Nucleic acid detection involving sensors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6816Hybridisation assays characterised by the detection means
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means

Abstract

A method for gene detection includes: chemically pretreating a plurality of magnetic sensors and combining the magnetic sensors with a biological probe, the magnetic sensors being in an arrangement of a matrix and comprised by a sensor module; disposing the magnetic sensors, which are combined with the biological probe, in a DC magnetic field and an AC magnetic field, and in contact 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; cleaning the magnetic sensors so that the DNA molecules to be detected that are not hybridized are removed; fixing the magnetic particles combined with the DNA molecules to be detected that are hybridized above the magnetic sensors so that a scattered magnetic field is formed and the reluctivity of the magnetic sensors varies under the scattered magnetic field; transforming variation of the reluctivity of the magnetic sensors into a signal representing a detection result of a DNA molecule to be detected by a signal processing chip.

Description

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 thedetection is relatively low and the detection is expensive and needs to be operatedby professional staff. In recent years, gene detection systems based on magneticlabels have been proposed and such systems are more stable, faster and easier tooperate compared 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 genedetection. In one aspect, the method for gene detection includes chemicallypretreating a plurality of magnetic sensors and combining the magnetic sensorsWith a biological probe, the magnetic sensors being in an arrangement of a matrixand included by a sensor module; disposing the magnetic sensors, Which arecombined With the biological probe, in a DC magnetic field and an AC magneticfield, and in contact With combined magnetic particles and DNA molecules to bedetected, so that the DNA molecules to be detected are matched and hybridized With the biological probe; Cleaning the magnetic sensors so that the DNA molecules to be detected that are not hybridized are removed; and fixing themagnetic particles combined With the DNA molecules to be detected that arehybridized above the magnetic sensors so that a scattered magnetic field is formedand the reluctivity of the magnetic sensors varies under the scattered magneticfield; transforrning variation of the reluctivity of the magnetic sensors into a firstelectrical signal by a signal processing chip; processing the first electrical signaland outputting a second electrical signal representing a detection result of a DNA molecule to be detected by the signal processing chip.
The signal processing chip includes a front-end circuit configured to transformvariation of the reluctivity of the magnetic sensors into a first electrical signal anda signal processing circuit configured to process the first electrical signal andoutput a second electrical signal representing a detection result of a DNA moleculeto be detected. The front-end circuit includes a row address selector and a columnaddress selector coordinated With each other and configured to allow the currentto floW into selected magnetic sensors. The front-end circuit further includes a pre-amplifier configured to amplify the electrical signal representing Variation of thereluctivity of the magnetic sensors so as to produce the first electrical signal. Thepre-amplifier includes a differential amplifier, a first clipper stabilizing circuit, asecond clipper stabilizing circuit, a third clipper stabilizing circuit, a first resistorand a second resistor. The differential amplifier includes a positive input port, anegative input port, a first positive output port, a first negative output port, asecond positive output port and a second negative output port. The first clipperstabilizing circuit is connected With the first positive output port and the firstnegative output port; the second clipper stabilizing circuit is connected With thesecond positive output port and the second negative output port; the third clipperstabilizing circuit is connected With the positive input port and the negative inputport; the positive input port is connected With the first negative output port throughthe first resistor; the negative input port is connected With the second negativeoutput port through the second resistor; the input signal of the differentialamplifier is an electrical signal output from the magnetic sensors and representing variation of the reluctivity of the magnetic sensors, and input through the positive2 input port and the negative input port; the output signals of the differentialamplifier include 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 may be connected Withthe ground through the third resistor and the first capacitor; the second negativeoutput port may be connected With the ground through the fourth resistor and the second capacitor.
In another aspect, the present patent application provides a method for genedetection. The method for gene detection includes chemically pretreating aplurality of magnetic sensors and combining the magnetic sensors With abiological probe, the magnetic sensors being in an arrangement of a matrix andincluded by a sensor module; disposing the magnetic sensors, Which are combinedWith the biological probe, in a DC magnetic field and an AC magnetic field, andin contact With combined magnetic particles and DNA molecules to be detected,so that the DNA molecules to be detected are matched and hybridized With thebiological probe; cleaning the magnetic sensors so that the DNA molecules to bedetected that are not hybridized are removed; fixing the magnetic particlescombined With the DNA molecules to be detected that are hybridized above themagnetic sensors so that a scattered magnetic field is formed and the reluctivity ofthe magnetic sensors varies under the scattered magnetic field; transformingvariation of the reluctivity of the magnetic sensors into a signal representing a detection result of a DNA molecule to be detected by a signal processing chip.
The sensor module is formed on a signal processing chip through sputtering. Thesignal processing chip includes a front-end circuit configured to transformvariation of the reluctivity of the magnetic sensors into a first electrical signal anda signal processing circuit configured to process the first electrical signal andoutput a second electrical signal representing a detection result of a DNA molecule to be detected. The front-end circuit includes a row address selector and a column3 address selector coordinated With each other and configured to allow the currentto flow into selected magnetic sensors, and a biasing Circuit and a pre-amplifier.The biasing circuit includes a plurality of diodes individually corresponding to theplurality of magnetic sensors; each diode is connected in series With acorresponding magnetic sensor so as to prevent the current from flowing intounselected magnetic sensors. The pre-amplifier includes a differential amplifier, afirst clipper stabilizing circuit, a second clipper stabilizing circuit, a third clipperstabilizing circuit, a first resistor and a second resistor; the differential amplifierincludes 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 negativeoutput port. The first clipper stabilizing circuit is connected With the first positiveoutput port and the first negative output port. The second clipper stabilizing circuitis connected With the second positive output port and the second negative outputport. The third clipper stabilizing circuit is connected With the positive input portand 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 signalof the differential amplifier is an electrical signal output from the plurality ofmagnetic sensors and representing variation of the reluctivity of the magneticsensors, and input through the positive input port and the negative input port; andthe output signals of the differential amplifier include a first output signal outputfrom 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 may be connected to theground through the third resistor and the first capacitor; the second negative outputport may be connected With the ground through the fourth resistor and the second capacitor. ln yet another aspect, the present patent application provides a system for gene detection. The system for gene detection includes a sensor module including a4 plurality of magnetic sensors in an arrangement of a matrix; and a signalprocessing chip configured to transform variation of the reluctivity of the magneticsensors into a first electrical signal, process the first electrical signal and output asecond electrical signal representing a detection result of a DNA molecule to bedetected. The signal processing chip includes a front-end circuit configured totransforrn Variation of the reluctivity of the magnetic sensors into a first electricalsignal and a signal processing circuit configured to process the first electricalsignal and output a second electrical signal representing a detection result of aDNA molecule to be detected. The front-end circuit includes a row addressselector and a column address selector coordinated with each other and configuredto allow the current to flow into selected magnetic sensors. The front-end circuitfurther includes a pre-amplifier configured to amplify the electrical signalrepresenting variation of the reluctivity of the magnetic sensors so as to producethe first electrical signal. The pre-amplifier comprises a differential amplifier, afirst clipper stabilizing circuit, a second clipper stabilizing circuit, a third clipperstabilizing circuit, a first resistor and a second resistor. The differential amplifierincludes 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 negativeoutput port. The first clipper stabilizing circuit is connected with the first positiveoutput port and the first negative output port; the second clipper stabilizing circuitis connected with the second positive output port and the second negative outputport; the third clipper stabilizing circuit is connected with the positive input portand 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 signalof the differential amplifier is an electrical signal output from the magnetic sensorsand representing variation of the reluctivity of the magnetic sensors, and inputthrough the positive input port and the negative input port; the output signals ofthe differential amplifier include 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 may be connected Withthe ground through the third resistor and the first capacitor; the second negativeoutput port may be connected With the ground through the fourth resistor and the second capacitor.
In yet 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 signal processing chip includes a front-end circuit configured totransform variation of the reluctivity of the magnetic sensors into a first electricalsignal and a signal processing circuit configured to process the first electricalsignal and output a second electrical signal representing a detection result of aDNA molecule to be detected. The front-end circuit includes a row addressselector and a column address selector coordinated With each other and configuredto allow the current to floW into selected magnetic sensors, and a biasing circuitand a pre-amplifier. The biasing circuit includes a plurality of diodes individuallycorresponding to the plurality of magnetic sensors; each diode is connected inseries With a corresponding magnetic sensor so as to prevent the current fromfloWing into unselected magnetic sensors. The pre-amplifier includes 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 includes a positive input port, a negative input port, a first positive outputport, a first negative output port, a second positive output port and a secondnegative output port. The first clipper stabilizing circuit is connected With the firstpositive output port and the first negative output port. The second clipperstabilizing circuit is connected With the second positive output port and the secondnegative output port. The third clipper stabilizing circuit is connected With thepositive input port and the negative input port. The positive input port is connectedWith the first negative output port through the first resistor. The negative input portis connected With the second negative output port through the second resistor. The input signal of the differential amplifier is an electrical signal output from the6 plurality of magnetic sensors and representing Variation of the reluctivity of themagnetic sensors, and input through the positive input port and the negative inputport; and the output signals of the differential amplif1er include a first output signaloutput from the first positive output port and a second output signal output from the second positive output port.
The pre-amplif1er may further include a third resistor, a fourth resistor, a firstcapacitor and a second capacitor; the positive input port may be connected to theground through the third resistor and the first capacitor; the second negative outputport may be connected With the ground through the fourth resistor and the second capacitor.
Brief Description of the Drawings FIG. 1 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-amplif1er of the system for gene detection as depicted in FIG. 1.
FIG. 7 is a flowchart illustrating a method for gene detection executed by thesystem as 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 patentapplication are described in detail, although it will be apparent to those skilled inthe relevant art that some features that are not particularly important to anunderstanding 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 genedetection disclosed in the present patent application is not limited to the preciseembodiments described below and that various changes and modifications thereofmay be effected by one skilled in the art without departing from the spirit or scopeof the protection. For example, elements and/or features of different illustrativeembodiments may be combined 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 of magnetic sensors 408 in an arrangement of a matrix. Each magnetic sensor 408 8 is formed by stacking layers of magnetic materials 408a, and the reluctivity ofeach magnetic sensor varies with the spin alignment of the electrons of two layersof magnetic materials 408a. When disposed in an extemal magnetic field, thereluctivity of the stacked magnetic materials 408a varies with the intensity of the extemal 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 ina DC magnetic field and an AC magnetic field and in sufficient contact with thecombined multiple magnetic particles and DNA molecules to be detected, so thatthe DNA molecules to be detected are matched and hybridized with the biologicalprobe. The multiple magnetic sensors 408 are then cleaned, and the DNAmolecules to be detected that are not hybridized are removed. The magneticparticles combined with the DNA molecules that are hybridized are relativelyfixed above the magnetic sensors 408, so that a scattered magnetic field can beformed. 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). Thesignal processing circuit 203 is configured to process the electrical signal andoutput a second 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 column address selector 405 includes multiple column switches. The multiple row9 switches and the multiple column switches are coordinated with each other,connected with 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 diodeis connected in series with a corresponding magnetic sensor 408 so as to preventthe current from flowing into unselected magnetic sensors 408. The configurationof the multiple 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 408can share the same biasing circuit 401 and the same pre-amplifier 409, whichreduces power consumption and system noise. At the same time, the noise of themagnetic sensors 408 is at the same order of magnitude as the smallest detectionsignal and the noise of the magnetic sensors 408 is determined by its own materialand structure, 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 asto produce the first electrical signal and the pre-amplifier 409 includes adifferential amplifier 501, a first clipper stabilizing circuit 503, a second clipperstabilizing circuit 505, a third clipper stabilizing circuit 507, a first resistor 509, asecond resistor 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, a first 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.AC signal) output from the multiple magnetic sensors 408, representing Variationof the reluctivity of the multiple magnetic sensors 408, and input into thedifferential amplifier 501 through the positive input port and the negative inputport. The output signal Vs of the differential amplifier 501 includes a first outputsignal Va and a second output signal Vb. The first output signal Va is output fromthe first positive output port. The second output signal Vb is output from thesecond positive output port. In this embodiment, the first output signal Va is an AC signal and the second output 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 505is connected With the second positive output port and the second negative outputport. The third clipper stabilizing circuit 507 is connected With the positive inputport and the 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 preventedDC current from flowing into a feedback loop and reduced the requirement for thedrive capability of the output port. The input impedance of the pre-amplifier 409is very high, so the input current is very small, Which further suppress the 1/f noise.The pre-amplifier 409 realizes AC coupling and DC coupling While remaining low noise.11 FIG. 7 is a flowchart illustrating a method for gene detection executed by thesystem as depicted in FIG. 1. The method includes the following steps: Step 601: magnetizing multiple magnetic particles With a DC magnetic field andan AC magnetic field; the DC magnetic field and the AC magnetic field can be established through an electrif1ed 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 aroundthe combined 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 611: cleaning the magnetic sensors first and remoVing the DNA molecules tobe detected that are not hybridized since the direct match of the DNA moleculesto be detected and the biological probe Will cause hybridization, and then relativelyfixing 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 12 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-amplif1erand clipper stabilizing circuits are used, which leads to high input impedance,small input 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 ofthe gene detection is improved. (3) Because all magnetic sensors share a biasingcircuit and a pre-amplif1er and the biasing circuit includes multiple diodes, thepower consumption 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 particularreferences to a number of embodiments thereof it should be noted that variousother changes or modif1cations may be made without departing from the scope of the present invention. 13

Claims (4)

What is claimed is:
1. A method for gene detection comprising: chemically pretreating a plurality of magnetic sensors and combining the magneticsensors With a biological probe, the magnetic sensors being in an arrangement ofa matrix and comprised by a sensor module; disposing the magnetic sensors, Which are combined With the biological probe, ina DC magnetic field and an AC magnetic field, and in contact With combinedmagnetic particles and DNA molecules to be detected, so that the DNA moleculesto be detected are matched and hybridized With the biological probe; cleaning the magnetic sensors so that the DNA molecules to be detected that arenot hybridized are removed; fixing the magnetic particles combined With the DNA molecules to be detectedthat are hybridized above the magnetic sensors so that a scattered magnetic fieldis formed and the reluctiVity of the magnetic sensors Varies under the scatteredmagnetic field; transforrning Variation of the reluctivity of the magnetic sensors into a signalrepresenting a detection result of a DNA molecule to be detected by a signalprocessing chip; Wherein: the signal processing chip comprises a front-end circuit configured to transformVariation of the reluctivity of the magnetic sensors into a first electrical signal anda signal processing circuit configured to process the first electrical signal andoutput a second electrical signal representing a detection result of a DNA moleculeto be detected; the front-end circuit comprises a row address selector and a column addressselector coordinated With each other and configured to allow the current to floWinto selected magnetic sensors, and a biasing circuit and a pre-amplifier; the pre-amplifier comprises a differential amplifier, a first clipper stabilizingcircuit, a second clipper stabilizing circuit, a third clipper stabilizing circuit, a first resistor and a second resistor; 14 the differential amplifier comprises a positive input port, a negative input port, afirst positive output port, a first negative output port, a second positive output portand a second negative output port; the first clipper stabilizing circuit is connected With the first positive output portand the 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 throughthe second resistor; the input signal of the differential amplifier is an electrical signal output from themagnetic sensors and representing variation of the reluctivity of the magneticsensors, and input through the positive input port and the negative input port; andthe 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.
2. The method for gene detection of claim 3, 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.
3. The method for gene detection of claim 1, Wherein the sensor module is formed on a signal processing chip through sputtering.
4. The method for gene detection of claim l, Wherein the biasing circuit comprises a plurality of diodes individually corresponding to the plurality of magnetic sensors, each diode being connected in series With a corresponding magnetic sensor so as to prevent the current from flowing into unselected magnetic sensors. 16
SE2130016A 2018-11-15 2018-11-15 Method for gene detection SE2130016A1 (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5776672A (en) * 1990-09-28 1998-07-07 Kabushiki Kaisha Toshiba Gene detection method

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5776672A (en) * 1990-09-28 1998-07-07 Kabushiki Kaisha Toshiba Gene detection method

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Ferreira, H.A. et al. (2003) Biodetection using magnetically labeled biomolecules and arrays of spin valve sensors (invited). Journal of Applied Physics 93(10): 7281-7286. *
Wang, H. (2013) Magnetic sensors for diagnostic medicine: CMOS-based magnetic particle detectors for medical diagnosis applications. IEEE Microwave Magazine, 14(5): 110-130 *

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