SE543509C2 - System and method for gene detection - Google Patents

System and method for gene detection

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Publication number
SE543509C2
SE543509C2 SE1830335A SE1830335A SE543509C2 SE 543509 C2 SE543509 C2 SE 543509C2 SE 1830335 A SE1830335 A SE 1830335A SE 1830335 A SE1830335 A SE 1830335A SE 543509 C2 SE543509 C2 SE 543509C2
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Prior art keywords
port
output
circuit
magnetic sensors
resistor
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SE1830335A
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Swedish (sv)
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SE1830335A1 (en
Inventor
Lanfang Xian
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Shenzhen Dansha Tech Co Ltd
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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

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Pathology (AREA)
  • Investigating Or Analyzing Materials By The Use Of Magnetic Means (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

A system ( 100) for gene detection includes a sensor module (101) including a plurality of magnetic sensors (408) in an arrangement of a matrix (407) and a signal processing chip (103) including a front-end circuit (201) and a signal processing circuit (103). The sensor module (101) is formed on the signal processing chip (103) through sputtering. The signal processing chip (103) includes a front-end circuit (201) configured to transform variation of the reluctivity of the magnetic sensors into a first electrical signal and a signal processing circuit (203) configured to process the first electrical signal and output a second electrical signal representing a detection result of a DNA molecule to be detected. The front-end circuit (201) includes a row address selector (403), a column address selector (405), a pre-amplifier (409) and a biasing circuit (401).

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 syes2ëerææ~n::eï,h .. .5 .J v» ^n<>~~lm> i/Cw w-w-F ~ »vs/i fn + :vwQ-vvw wn-vflxfif» Frll - lxn/Fvšh F fÉ-Å » fxn- if~í.sx~\wxfo._lt.nt, 'msk :.L)_).ö1¿1\; z u. 1.5 1:10: :Lu x u: mixa: \.>L mi; .xwxuvxsvlc \.>: .x .xisuyåjiapwi :Yxn n v'* 1-9 f - *Fwuf .iaflfri al ii* s fal 1f\~ m, *r fl a ~ f 'Alfa ir 'Oral 'f :fx-l and x f! x f <1ou: -. o 1 i i 11 o ~ v va; 1.5 ä, 1 ., pxxi 4.:-, u. Lau Li. -s vu; Lib s: s x: x k; x s 1 nlutaläittf of iiiagnetite sensnrs and cnrnhiiiitng the rnagnetic sensnrs With a biological probe, the inaflnetie sensors being in an ariangenaent of a matrix and included hv a sensor modulef-L disposine tilïhe magnetic sensors nïâiieli are andenmhiiíleal :with the biological probe,_ ' = ' . in a DC magnetic field and an AC magnetic field, and in .j " contact With combined magnetic particles andDNA molecules to be detected, so that the DNA molecules to be detected are matched and hybridized With the biological probef; eleaiiiiigf tïllhe t , " Ümagnetic sensors-aéie-iç-lieii-e-l-eafiieal-so that the DNA molecules to be detected that are not hybridized areremoved; and šganiiidgwthe magnetic particles combined With the DNA molecules to bedetected that are hybridized f above the magnetic sensors so that ascattered magnetic field is formed and the reluctivity of the magnetic sensors Varies under the scattered magnetic fieldf trarisiioirniifig Xfztriatiitii nf the rteltictilwitsf ot" the rnagnetic serisfßts :inte a first eleetriczil signal hv a sif>nal preeessirig chip* processing the first electric-ai signal arid eutpiittitnffl a second electrical signal tentesentitnffi a detection result of a DNA nieieeule tn be detected liv the signed lnrneessing chip.
(D. a.
The signal processing chip tiiafiihincludes a front-end circuit configured to transformVariation 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 niaæincludes 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 æfæïwfurther include; a pre-amplifier configured to amplify theelectrical signal representing variation of the reluctivity of the magnetic sensors so asto produce the first electrical signalT-anë, tåwwßpre-amplifier incii1des adifferential amplifier, a first clipper stabilizing circuit, a second clipper stabilizingcircuit, a third clipper stabilizing circuit, a first resistor and a second resistor;~.__",_fj1he differential amplifier _, ,j _i_r;_ç_l__g:_g§_e§__a positive input port, a negative input port, a first positive output port, a first negative output port, a second positive output portand a second negative output port-;---.mt-l=:e---:§Å3¿ç__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 negativeinput port is connected With the second negative output port through the secondresistor; the input signal of the differential amplifier is an electrical signal output fromthe magnetic sensors and representing variation of the reluctivity of the magneticsensors, and input through the positive input port and the negative input port; theoutput signals of the differential amplifier iracšaaide 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 ifæniawf he connected With theground through the third resistor and the first capacitor; the second negative outputport ælsfrg;_gz_y__fg_e__connected With the ground through the fourth resistor and the second capacitor. i ff' ÄVÄÄ-Ä 'FIA F »+ I Å MW-m kr » -w Åfnwiqnv 2% IfM-ln n ïšnU-f 'fmnk- +§ ~ L-.U-fwwx, xxx! x man: 'u u xxx y x.. xx v x vx..uv s f un: Jb vx ._ x 3, xx xoxkx Z? .~.Q»\~»~«~- A nnh »l »Ä e» www, f: -l vi ~ v* ~~ fri .- nnfl- wa »\A=»\ - vwfw fw» f. v-fv ~» fwovan.. to, WVJ: A: 4 10 ' :Jalvw mn 1:1 n L: ._ 11:14: Lvxuxlwhi :lxLul :u :E31 :vn 'ln l ._ M-V.. f, www f» fri a v--D (riff-avta f! w -mnf if u waif-l ífafïl i fy» f» f~ ~avw v~i] V ÄÃ Ä ÛÄÃVÄà *Äli/ S, \.4'à fV Ä! E, l Ä f K/L ÃL \/! 'i/ ' ÃÃÉÄ/n Ä å. \)\J k 1 In another aspect, the present patent application provides a systenflnethocl for gene detection. The sfißsëeæafnfiaätlzrvaå for gene detection includes f se f wii 1» iår» ~ 47%.- ~ s 4%. -. »v w k» fy» .-,~.~. y ~ v m1- F» v . 1- -šv- “m4 f .VV f! a. a.) m3 =»v i :\:,cc::_u,y v: 1:: 11.5: n.. mv u\ø::.. :u :u M4: uicuuw u). .u c- .L u, Lux: ut: \,, »Lun M Qufiu w: l_,ø.vv\ø..»_n_:xó 1 chemically Qretrealtting a: píuralittw' of rnagnetic serisors and efßnabi-freël--erznibimina: the niagfaetic sensors With a .1 biological probe, the nïasznetic sensors being in an arrangenient of a nïatrix andincluded. hv a sensor :moduler f disrposiiiff tThe magnetic sensors vøhich are afiëfcombined mfith the biological probei a DC magnetic field and an AC magnetic field, and in f _ i contact With combined magnetic particles andDNA molecules to be detected, so that the DNA molecules to be detected are matchedand hybridized With the biological probe.~: cleariirigfig' tllihe magnetic sensorsafe--then--e-É-eaneá--so that the DNA molecules to be detected that are not hybridized areremoVedf-L fixirng tílïhe magnetic particles combined With the DNA molecules to be detected that are hybridized f 2 above the magnetic sensors so that ascattered magnetic field is forrned and the reluctiVity of the magnetic sensors Varies under the scattered magnetic fieldf; trimsforntzitnsf vaifiatior: of the re}1,:c1iíx~'iï>y of the nxagftietis: sensors into a signal r'e§1n'ese1'1tir1<>' a deteettizarl result of a lflšNf-ä :molecule to be detected by a signal processing chip, The sensor module is formed on signal processing chip through sputtering. Thesignal processing chip includes a front-end circuit configured to transforrn Variationof the reluctiVity of the magnetic sensors into a first electrical signal and a signalprocessing circuit configured to process the first electrical signal and output a secondelectrical signal representing a detection result of a DNA molecule to be detected. Thefront-end circuit includes a row address selector and a column address selector coordinated With each other and configured to allow the current to floW into selected 4 magnetic sensors, and a biasing Circuit and a pre-amplifier. The biasing circuitincludes a plurality of diodes individually corresponding to the plurality of magneticSensors; each diode is connected in series With a corresponding magnetic sensor so asto prevent 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 a secondresistor; the differential amplifier includes a positive input port, a negative input port,a first positive output port, a first negative output port, a second positive output portand a second negative output port. The first clipper stabilizing circuit is connectedWith the first positive 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 the positiveinput port and the negative input port. The positive input port is connected With thefirst negative output port through the first resistor. The negative input port isconnected With the second negative output port through the second resistor. The inputsignal of the differential amplifier is an electrical signal output from the plurality ofmagnetic sensors and representing variation of the reluctivity of the magnetic sensors,and input through the positive input port and the negative input port; and the outputsignals of the differential amplifier include a first output signal output from the firstpositive 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 first capacitor and a second capacitor; the positive input port ifærriaxf be connected to the ground through the third resistor and the first capacitor; the second negative output port 'ne connected With the ground through the fourth resistor and the second capacitor. ih tfet aiitittiei* asraeizt the :present tiateht anraiieatitiri nttitfities a: stfsterii ter izeriedeteetien. "tiie stfsteiti fnr :fehe detection includes a sensor hteduíe iiieiudiiit: a hhttaiitxf ef matftietie seiisers iii ah attahffemeht nt" at matrix; and :i siflnaii nroeessiiis: Chin tfieiíifitfttiíeti te ttzitisføttii wtriz-ttioti et* tiie rehietitaittf ef the iítiztgiietit: sensers iiitn :t tirst eteetriieat sißiiizti. tiretress the .tirst eteetrittat siizriai artrit tiutteiaiti a: second. eieattrieaii sigriat represeniting tteteetiitih .restthi et' a: DNA, rrieietttite te be fíetietf-teti. The siznaft titneessitiß' ehiiß irieiiities tt tretitæerid eireiiit etihfifttitetí te tiatisthtin ifttriatitiit of the reiuetitfittf efthe rnttïtnetie sensets ittte a. first eieetrieai sinnet and a: siizriai *tireeessiiriffi eitetiit eeiifietirett te iimeess the first eieetrieai sigiiai and eiitnuit a seeehd eieettiettisitfiiai reiireseiitiiit: :i tteteetittii result ef :i DNA ineieeiiie te he tteteeted. The tifont~ end eiitfuit iiieiiides :i rmtf :tdtiress seieeter and eehizrhn :idtitess seieettii' eeerttiiíinted. with ezten titther :ttuí etmtitziareti te nätets) the tfiurrent, te .tittar iritn selected niiufhetie setisers. 'the titiht-erid Circuit tiirthei' iirieittties tt nre-ziriiniifiet eehtïfiured te tttnïaiiftf the eieetrieai siizhai renresetitinv ifttriatieit of the *rehtetitfittf ef the tnafirietie seiisttrs se :is to htedtiee the first eiectiieai sitzhai. "Pite iiieætiniiiitiei' eniiiiiiises a diffeieiitiai aiiitiiifiet, :i first eiinriei' staiiiiiziitt: eitettit tt seeend eiiiitiei' stahiiiziiië eiitttiit a third charter stnhiiiziiíit: eircuit, :t first resistei" :iiiti :i seeøtití resiatør, Tile tiiffereiíitiziiittmfititiei" itrattuti-es :t tfitisitiwe irinut htrrt. i:ies':iit,i\-=e ihnttt hett. :i 'first tmsitiitfte titithtit port. a .tirst tiet-witive titrtratat htirt. :t seeehd tfitisitiitae nutriut, nnrt :and :t seenriti riegmtiitfe tiitttiiit hett. 'the first eiiritßet sttthiiiiziiii: eirsziiit is etihtieetefi “With the tirst 'tiesititfefititiitit iinit and the first iietfatii/e ntittiitt iinit; the seeehd eiiniiei' stahiiizinfi eiretiit iseeiiiteeted tvith the seeehd hesitive eiithut hett and the seenhd hefatitfe output nnit'the third eiiitgfiei" stahiiiziiiff eiitsuit is; eeiiiietfited tvith the nesitixfe ihnut hett and the rietizttive i rirïitit nnrt; the eesiitive irirïrtit, nert is ttniiheaf-ttizà tafith: the tittat, negativt: eittmtt rïrtirt tthrtitiilïti the tirst, resistnr* tihe rieizatittfte itrhtit port is etituieeteti. with the. second. hevtttitfe tiiittiirt nert tïhrfiiiati the seeenti resister; the iirinut sinnet nt tlhe tíiffeteiitiai ziriiniifiei” is en eieetriszai sigfrizii tititritit frun: tïhe rhaniietie seustirs :the retiteseritiits: vatiatieii ef the reiuetivitv nt" the matzhetie sehsfits. and iniitit thrøti-:Iii tiie hesitii/e iiihiit imtt and the he-'fative iiihut hett: the outnut sifnais; ef the tiiffereiíitizii ztmtehtiei' 6 inehide a first iiiltnilt siffrrai tiiittiitt tiisrn the first 'tiosititfe oiittiitt nort :md a second outnutt stina! rititnut front the second tiositixte outnnt nort.
The nroanrnhfier inay ftirtliet' inehltie a thírti resistoiy a 'fourtir resistoi; a 'first ttztnztei tor atiti a sectonri caitna-ztitioit* the ifitisitittftä irinnt, ntirt irrziy he connected ttfith tiie tïroitiirí thioiatzti the third. resistoi' :Anti the first -ztztnftcittirt the stä-:ttrtiti nenatifat? statestit titirt nian' he cniiriectefš *faith the tiroiniti titrotieh the ttitnth resistor aiiti the second canaeitor. in vet another aspect; the nresent natent annheation nrovities a svstern ter eene cieteetioiït. The svsteni tor ttetectitiiíi níieittties sensor rnodnle including a tïfiitrztiitsf of nriasftietic serisors i n an zitrrzitrißzerrtertrti of niatrixt and a sinnai nroeessintl: ehin. 'the sinnet tiroeessiiie chin ineiutíes a tionïæerití cirenit coritietiretí to trzinsforrn *Jariatiori of the rehtetitffitïf of the tiiaerietie sensorn into a first eiectrieai siffriai :and a startat nrocessiin: eircuit eonfietired to iriroeess the first eteetricaš sienai and outnutt a second eieetrieai signaš renresentiiit: a cteteetion resuftt of a DÜNÄA rnoiecuie to he detected. The tront~en<í circuit iiíieitities a row' atttiress selector anti a cohiniii atttiress sekä-Liter eoertíiriztteti. xtfith :etch otihei' :iiiti eoiitir-*Ltreti to aííriiw' the citrrent to tittat' iiitti seteeteri niasftïiet,ie Sensors, :iiirí a hiatsintz :institutet and a nre-zirnniifitär. The hiasitnrfl citretiit ineiutíes a tiiuraiittw' of ftioties iridixfititiaitsf corresnoiitiirie to the titurnítiti/ of rnaigrietie sensors; eaeh diode is connected in series tvith a eorresnoiiàiiit: matznetic sensor' so to nrevent the current froin fiowtfinfi into tinseíeeteci iriafinetic serisors.
The nrtæanítißiifier iiísttttties a tiifferential arnnhfiei; a first eiinrier* stahiíizine citeuit, a seeoiiti eiinner staifitiiziiriti' circtiit. a ttiitfti eiinnei' stahttiziiria eircitit., a first, resistor atïid. a second resistor: the riitterentizti arnigàaïijíïter inttftudes tïsositiive irintit ifrotft. at 1:iet>'at,i\fe inrint eort, a first rtiositisfe outinn nort a first riesïatitfe tiiltnilt finit. a second nositiwfe oiltnut :sort and a second riesïatitflfe tiiltniit nort. "the first eiinner stahiiiziiiß' cirenit is; connected *Jtfith the first nositixfe onttint non: and the first negative tnttnttt nort. 'fhe second tfiintner' stahiiiziinf eirtfuit is etinneeted wtfith the second nositiflre ottttntit tion. strid the seetmd twefiatšve eutettt hett. The third ehnher stahiíizšttg Circuit is eehtxeetecí»Xfíth the ttesítšve šnnttt hett and the hetfative šnntit hett, The teesitiïte innut hett iscflhheeted :with the first ttefiative tättthut hett threufiftï the fitst register. The nefiativetunnt tætatt is centítetfited æt-fíth the secctnd negative eutptxt :tera through the second iesister. The inçmt signal Of the diífíiäiftätttitztl atneiiíïezt is at: eåeatttical signed ttutgfitxt íïterh the gcwïuraiithy etfnttasffttetic sen stuff; attd. tftïqfit.'täsehtiítta “æfatitttiítzn utïftte tfešjutïtíxfit“sf att'the htaftttetit: settaers, :md intmt thtettsïh the nesítiwfe iheut hett and the tteftattiïfe itïhutetfrt: and the euthut sisïneís; fstftltte fíifferetttittt ettxtgfiíitfíet' include a tfhfst euthut síftnaíftutettt frenï the tïrst hesitíwe tattthttt hett anti e seeonà ettthut stan-at fftttnttt frem the setfenå hesíttwfe etttpttt hart.
The htts-zttnnh'ñer .miw tïtrther inchaàe a. tthftà ttïsístot", :z íettrttt tesister. a. ñfstceheeittßt että a seeettfí eahzuzíter' the hesíttwte input hett tnzw he catnneszteti tt: the*Iteuttfš tlhrfflxah the third tesíster että the first szeheeiteï: the seetshd tlefiatšve etlthut hett mzw *se eenneeteci with the :Hound through the fourth resistor and the second eegfieeíttät. ~ t -tkš-C-t v 4% -f f» w» '” . ~ t- -t -,-,~ ufšfift. kt' i -šwl tf-.t- . ~+« v. /1- fiffklš á ”v t + - VM*\,-x,¿;:>-.\:n.::ß ut u-Jufßhm/v), ß unvt- W :nu u, vtvtx: tva: rat 1, »5 ß 'vy f, - ~.:+u::,3:_t;,:,t.- vu. .tax- v.-tf-1-š~¥§!¿. ä'i-\>f\{'”ftf.-tf t-š~t'ífïåtn--tf -ffi Uf»-Lmnsašth t-txf ttvæ. t u. u utv .c x\_/ :Lxcafšth t-txf t tv). t sftfhut/t: . vu. u.- xuø wmumr. ~ -vi 'ft â-f f. -f tf» ~-f IIJL .LI För L (JJMIQ (J. v). ._ hä? šh-i f«-~ .-« 1 -flf-"i å; 'u 'l f -tå -mfkhá v t w wšt~ftï .-~ ii 1- ~+ tf,utxfnxmvçtx-'wa EJAUL/ »n \,t\«u\=::.1,\.« t u.) Qvx-Ã. f.) afutx: -I.:4«u::,3:_t)_:_t.- »tf uhßøJufh uuø :UJVQ »JL i ut. few Vt» ~ t-Efv f-v kk -1 Û. íÅ m» i>~-»I-.~ 1-~ h -1 t- ~« ~1 - - tf ~ f -tf\,&I^ EJCrÄICAI-L ß-J.I\/ \JI1J.{/l(l .\)_ICC\W\~'L$), ^ l- ß . k. ~' t. k. f - x v nu .tfn w . 2. U L-x- u -x- fix/mr. :t.t Lust J' ~---,-§“§f-.« Å in m t W m fi» ~~. -f 'tf-d «~ltf f» tf» ftff. . .yä 5"! JM v.\å\/._ tiuvm). Lu -u vx) t-.uv vvtJJutJJvxå Luufç . w. Qvllß in uußvt L 1 1 b), ut y '. .~.l “v ' 1 1141; ~ l» -f 51* f' f f» v år" .m.. vtx-»Lu .Ö c-.uv 'kzunzc-mnfdf :_ nazurß. vw. w i, “all-m + i s åflfvuw' sl få ff- .n--Ä -1- iwkf 1"» »NI f så 'l-s ss -1_ ff; ,\i- (få -" Å» v i-l»1.: :\:.\x.. m: »J 1, 1.1.. 41.4, vvuu; »Lu-Lv “nu .uuc- u.) :amam \a.,¿ autx: u:\ø:: .xvu-u, .c vil .\.\1\:.::ß u, a v . -y w, ~ . ma. J mIJJÅJEKA š-(ï-f i. E44 -&\/). ^ Ä-sffinff »w fun :If naeH-w, YEYXT S. ifs x i»J» \,«'\«} ll l L ÛÅ). \~_( (l Ä. L Yi ' f . :i \:xw ~ + ha 14119,, :ÅA x “k fï-f» 'Ån- ni vwn »_ cv w u n; 'vv-u vv s: .u iaibm .i V: 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 of thesystem and method for gene detection disclosed in the present patent application aredescribed in detail, although it will be apparent to those skilled in the relevant art thatsome 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 an embodiment 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 ofmagnetic materials 408a. When disposed in an extemal magnetic field, the reluctivityof 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 the figures).The combined magnetic sensors 408 and biological probe are disposed in a DCmagnetic field and an AC magnetic field and in sufficient contact With the combinedmultiple magnetic particles and DNA molecules to be detected, so that the DNAmolecules to be detected are matched and hybridized With the biological probe. Themultiple 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). 11 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 addressselector 405 includes multiple column switches. The multiple row switches and themultiple column switches are coordinated with each other, connected with an extemalpower supply VDD, and configured to allow the current to flow into selected magnetic sensors 408.
The biasing circuit 40l includes multiple diodes. The multiple diodes are individuallycorresponding to the multiple magnetic sensors 408 and each diode is connected inseries with a corresponding magnetic sensor 408 so as to prevent the current fromflowing into unselected magnetic sensors 408. The configuration of the multiplediodes helps to improve the accuracy of the system for gene detection l00 and reduce power consumption.
Because one magnetic sensor 408 is selected at a time, all magnetic sensors 408 canshare the same biasing circuit 40l 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 and thenoise of the magnetic sensors 408 is deterrnined by its own material and structure, andtherefore 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 electrical signalrepresenting Variation of the reluctivity of the magnetic sensors 408 so as to producethe first electrical signal and the pre-amplifier 409 includes a differential amplifier 50l, a first clipper stabilizing circuit 503, a second clipper stabilizing circuit 505, a 12 third clipper stabilizing circuit 507, a first resistor 509, a second resistor 511, a thirdresistor 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 second output signal Vb is a DC signal.
The first clipper stabilizing circuit 503 is connected With the first positive output portand 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 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 negative outputport through the second resistor 511. In addition, the positive input port is connectedto the ground through the third resistor 510 and the first capacitor 513 and the second negative output port is connected to the ground through the fourth resistor 512 and 13 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 clipper stabilizingcircuit 505 and the third clipper stabilizing circuit 507 loWers 1/f noise. The firstcapacitor 513 and the second capacitor 515 have effectively prevented DC currentfrom flowing into a feedback loop and reduced the requirement for the drive capabilityof the output port. The input impedance of the pre-amplifier 409 is Very high, so theinput 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.
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 the combined magnetic sensors and biological probe as described in the step 605, and establishing a signal baseline; 14 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 to bedetected that are not hybridized since the direct match of the DNA molecules to bedetected and the biological probe will cause hybridization, and then relatively fixingthe 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 a firstelectrical 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 electrical signalrepresenting 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, the systemand the method provided by the present patent application have the followingadvantages. (1) The signal processing chip 103 is formed on the sensor module 101through sputtering, which contributes to good yield, high sensitivity, low parasiticcapacitance, good scalability, smaller size of the system and stronger anti-interferencecapability (especially the capability of resisting electromagnetic interference). (2) Allmagnetic sensors share a biasing circuit and a pre-amplifier and clipper stabilizingcircuits are used, which leads to high input impedance, small input current, and furthersuppressed 1/f noise, so that the noise of the signal processing chip 103 is lower thanthat of the sensor module and the sensitivity of the gene detection is improved. (3) Because all magnetic sensors share a biasing circuit and a pre-amplifier and the biasing circuit includes multiple diodes, the power consumption of the system forgene 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 Various otherchanges or modifications may be made Without departing from the scope of the present invention. 16

Claims (8)

What is claimed is:
1. A method for gene detection comprising: chemically pretreating a plurality of magnetic sensors (408) and combining themagnetic sensors (408) With a biological probe, the magnetic sensors (408) being inan arrangement of a matrix (407) and comprised by a sensor module (101);disposing the magnetic sensors (408), Which are combined With the biological probe,in a DC magnetic field and an AC magnetic field, and in contact With combinedmagnetic particles and DNA molecules to be detected, so that the DNA molecules tobe detected are matched and hybridized With the biological probe; cleaning the magnetic sensors (408) so that the DNA molecules to be detected thatare not hybridized are removed; and fixing the magnetic particles combined With the DNA molecules to be detected thatare hybridized above the magnetic sensors (408) so that a scattered magnetic field isformed and the reluctivity of the magnetic sensors (408) Varies under the scatteredmagnetic field; transforrning Variation of the reluctivity of the magnetic sensors (408)into a first electrical signal by a signal processing chip (103); processing the first electrical signal and outputting a second electrical signalrepresenting a detection result of a DNA molecule to be detected by the signalprocessing chip (103); Wherein: the signal processing chip (103) comprises a front-end circuit (201) configured totransforrn Variation of the reluctivity of the magnetic sensors (408) into a firstelectrical signal and a signal processing circuit (203) configured to process the firstelectrical signal and output a second electrical signal representing a detection resultof a DNA molecule to be detected; the front-end circuit (201) comprises a row address selector (403) and a columnaddress selector (405) coordinated With each other and configured to allow the current to flow into selected magnetic sensors (408); the front-end Circuit (201) further comprises a pre-amplifier (409) configured toamplify the electrical signal representing variation of the reluctivity of the magneticsensors (408) so as to produce the first electrical signal; the pre-amplifier (201) comprises a differential amplifier (501), a first clipperstabilizing circuit (503), a second clipper stabilizing circuit (505), a third clipperstabilizing circuit (507), a first resistor (509) and a second resistor (511); the differential amplifier (501) comprises a positive input port, a negative input port,a first positive output port, a first negative output port, a second positive output portand a second negative output port; the first clipper stabilizing circuit (503) is connected With the first positive output portand the first negative output port; the second clipper stabilizing circuit (505) is connected With the second positiveoutput 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 the firstresistor (5 09); the negative input port is connected With the second negative output port through thesecond resistor (511); the input signal of the differential amplifier (501) is an electrical signal output fromthe magnetic sensors (408) and representing variation of the reluctivity of themagnetic sensors (408), and input through the positive input port and the negativeinput port; and the output signals of the differential amplifier (501) comprise a first output signaloutput from 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 1, Wherein the pre-amplifier (201) furthercomprises a third resistor (510), a fourth resistor (512), a first capacitor (513) and a 16 second capacitor (515); the positive input port is connected With the ground throughthe third resistor (510) and the first capacitor (513); the second negative output portis connected With the ground through the fourth resistor (512) and the secondcapacitor (515).
3. A method for gene detection comprising: chemically pretreating a plurality of magnetic sensors (408) and combining themagnetic sensors (408) With a biological probe, the magnetic sensors (408) being inan arrangement of a matrix (407) and comprised by a sensor module (101);disposing the magnetic sensors (408), Which are combined With the biological probe,in a DC magnetic field and an AC magnetic field, and in contact With combinedmagnetic particles and DNA molecules to be detected, so that the DNA molecules tobe detected are matched and hybridized With the biological probe; cleaning the magnetic sensors (408) so that the DNA molecules to be detected thatare not hybridized are removed; fixing the magnetic particles combined With the DNA molecules to be detected thatare hybridized above the magnetic sensors (408) so that a scattered magnetic field isformed and the reluctivity of the magnetic sensors (408) varies under the scatteredmagnetic field; transforrning variation of the reluctivity of the magnetic sensors (408) into a signalrepresenting a detection result of a DNA molecule to be detected by a signalprocessing chip (103); Wherein: the sensor module (101) is formed on a signal processing chip (103) throughsputtering; the signal processing chip (103) comprises a front-end circuit (201) configured totransforrn variation of the reluctivity of the magnetic sensors (408) into a firstelectrical signal and a signal processing circuit (203) configured to process the firstelectrical signal and output a second electrical signal representing a detection result of a DNA molecule to be detected; 17 the front-end circuit (201) comprises a row address selector (403) and a columnaddress selector (405) coordinated With each other and configured to allow the currentto floW into selected magnetic sensors (408), a biasing circuit (401) and a pre-amplifier (409); the biasing circuit (401) comprises a plurality of diodes individually corresponding tothe plurality of magnetic sensors (408), each diode being connected in series With acorresponding magnetic sensor (408) so as to prevent the current from flowing intounselected magnetic sensors (408); the pre-amplifier (201) comprises a differential amplifier (501), a first clipperstabilizing circuit (503), a second clipper stabilizing circuit (505), a third clipperstabilizing circuit (507), a first resistor (509) and a second resistor (511); the differential amplifier (501) comprises a positive input port, a negative input port,a first positive output port, a first negative output port, a second positive output portand a second negative output port; the first clipper stabilizing circuit (503) is connected With the first positive output portand the first negative output port; the second clipper stabilizing circuit (505) is connected With the second positiveoutput 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 the firstresistor (5 09); the negative input port is connected With the second negative output port through thesecond resistor (511); the input signal of the differential amplifier (501) is an electrical signal output fromthe magnetic sensors (408) and representing variation of the reluctivity of themagnetic sensors (408), and input through the positive input port and the negative input port; and 18 the output signals of the differential amplifier (501) comprise a first output signaloutput from the first positive output port and a second output signal output from the second positive output port.
4. The method for gene detection of claim 3, Wherein the pre-amplifier (201) furthercomprises a third resistor (510), a fourth resistor (512), a first capacitor (513) and asecond capacitor (515); the positive input port is connected to the ground through thethird resistor (510) and the first capacitor (513); the second negative output port isconnected With the ground through the fourth resistor (512) and the second capacitor(5 15).
5. A system (100) for gene detection comprising: a sensor module (101) comprising a plurality of magnetic sensors (408) in anarrangement of a matrix (407); and a signal processing chip (103) configured to transforrn variation of the reluctivity ofthe magnetic sensors (408) into a first electrical signal, process the first electricalsignal and output a second electrical signal representing a detection result of a DNAmolecule to be detected; Wherein: the signal processing chip (103) comprises a front-end circuit (201) configured totransforrn variation of the reluctivity of the magnetic sensors into a first electricalsignal and a signal processing circuit (203) configured to process the first electricalsignal and output a second electrical signal representing a detection result of a DNAmolecule to be detected; the front-end circuit (201) comprises a row address selector (403) and a columnaddress selector (405) coordinated With each other and configured to allow the currentto floW into selected magnetic sensors (408); the front-end circuit (201) further comprises a pre-amplifier (409) configured toamplify the electrical signal representing variation of the reluctivity of the magnetic sensors (408) so as to produce the first electrical signal; 19 the pre-amp1ifier (201) comprises a differential amp1ifier (501), a first c1ipperstabi1izing Circuit (503), a second c1ipper stabi1izing circuit (505), a third c1ipperstabilizing circuit (507), a first resistor (509) and a second resistor (511); the differential amp1ifier (501) comprises a positive input port, a negative input port,a first positive output port, a first negative output port, a second positive output portand a second negative output port; the first c1ipper stabilizing circuit (503) is connected With the first positive output portand the first negative output port; the second c1ipper stabilizing circuit (505) is connected With the second positiveoutput port and the second negative output port; the third c1ipper stabi1izing 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 the firstresistor (5 09); the negative input port is connected With the second negative output port through thesecond resistor (511); the input signa1 of the differentia1 amp1ifier (501) is an e1ectrica1 signa1 output fromthe magnetic sensors (408) and representing variation of the re1uctivity of themagnetic sensors (408), and input through the positive input port and the negativeinput port; and the output signa1s of the differentia1 amp1ifier (501) comprise a first output signa1output from the first positive output port and a second output signa1 output from the second positive output port.
6. The system (100) for gene detection of c1aim 5, Wherein the pre-amplifier (201)further comprises a third resistor (510), a fourth resistor (512), a first capacitor (513)and a second capacitor (515); the positive input port is connected With the ground through the third resistor (510) and the first capacitor (513); the second negative output port is connected With the ground through the fourth resistor (512) and thesecond capacitor (515).
7. A system (100) for gene detection comprising: a sensor module (101) comprising a p1ura1ity of magnetic sensors (408) in anarrangement of a matrix (407); and a signal processing chip (103); Wherein: the signa1 processing chip (103) comprises a front-end circuit (201) configured totransforrn variation of the re1uctivity of the magnetic sensors into a first e1ectrica1signa1 and a signa1 processing circuit (203) configured to process the first e1ectrica1signa1 and output a second e1ectrica1 signa1 representing a detection resu1t of a DNAmo1ecu1e to be detected; the front-end circuit (201) comprises a row address se1ector (403) and a co1umnaddress se1ector (405) coordinated With each other and configured to a11oW the currentto floW into se1ected magnetic sensors (408), a biasing circuit (401) and a pre-amp1ifier (409); the biasing circuit (401) comprises a p1ura1ity of diodes individua11y corresponding tothe p1ura1ity of magnetic sensors (408), each diode being connected in series With acorresponding magnetic sensor (408) so as to prevent the current from floWing intounse1ected magnetic sensors (408); the pre-amp1ifier (201) comprises a differentia1 amplifier (501), a first c1ipperstabilizing circuit (503), a second c1ipper stabi1izing circuit (505), a third c1ipperstabilizing circuit (507), a first resistor (509) and a second resistor (511); the differentia1 amp1ifier (501) comprises a positive input port, a negative input port,a first positive output port, a first negative output port, a second positive output portand a second negative output port; the first c1ipper stabilizing circuit (503) is connected With the first positive output portand the first negative output port; 21 the second c1ipper stabi1izing circuit (505) is connected With the second positiveoutput port and the second negative output port; the third c1ipper stabi1izing 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 the firstresistor (5 09); the negative input port is connected With the second negative output port through thesecond resistor (511); the input signal of the differential amp1ifier (501) is an e1ectrica1 signa1 output fromthe magnetic sensors (408) and representing variation of the re1uctivity of themagnetic sensors (408), and input through the positive input port and the negativeinput port; and the output signa1s of the differentia1 amp1ifier (501) comprise a first output signa1output from the first positive output port and a second output signa1 output from the second positive output port.
8. The system (100) for gene detection of c1aim 7, Wherein the pre-amp1ifier (201)further comprises a third resistor (510), a fourth resistor (512), a first capacitor (513)and a second capacitor (515); the positive input port is connected to the groundthrough the third resistor (510) and the first capacitor (513); the second negativeoutput port is connected With the ground through the fourth resistor (512) and thesecond capacitor (515). 22
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