Kev ntsuam xyuas DNA methylation ua ke nrog cov xov tooj smartphones rau kev tshuaj xyuas ntxov ntawm cov qog thiab kuaj ntshav leukemia nrog qhov tseeb ntawm 90.0%!

Kev kuaj pom ntxov ntxov ntawm kev mob qog noj ntshav raws li cov kua dej biopsy yog ib qho kev taw qhia tshiab ntawm kev kuaj mob qog noj ntshav thiab kuaj pom los ntawm US National Cancer Institute nyob rau xyoo tas los no, nrog rau lub hom phiaj ntawm kev kuaj mob qog noj ntshav thaum ntxov lossis txawm tias muaj kab mob precancerous. Nws tau dav siv los ua ib qho tshiab biomarker rau kev kuaj mob ntxov ntawm ntau yam malignancies, nrog rau mob ntsws cancer, qog nqaij hlav hauv plab, gliomas thiab gynecological qog.

Qhov tshwm sim ntawm cov platforms los txheeb xyuas cov toj roob hauv pes methylation (Methylscape) biomarkers muaj peev xwm txhim kho kev kuaj mob qog noj ntshav thaum ntxov, muab cov neeg mob nyob rau theem kho tau ntxov tshaj plaws.

Tsis ntev los no, cov kws tshawb fawb tau tsim ib qho yooj yim thiab ncaj qha kev soj ntsuam platform rau methylation toj roob hauv pes nrhiav kom tau raws li cysteamine decorated kub nanoparticles (Cyst/AuNPs) ua ke nrog ib tug smartphone-based biosensor uas ua rau kom sai sai ntawm cov qog nqaij hlav. Kev tshuaj xyuas ntxov rau tus kab mob leukemia tuaj yeem ua tiav hauv 15 feeb tom qab DNA rho tawm los ntawm cov ntshav kuaj, nrog qhov tseeb ntawm 90.0%. Cov npe kab lus yog kev tshawb nrhiav sai ntawm cov qog nqaij hlav DNA hauv tib neeg cov ntshav uas siv cysteamine-capped AuNPs thiab lub tshuab kev kawm-tau siv smartphone.

Daim duab 1. Ib qho yooj yim thiab ceev lub platform rau kev kuaj mob qog noj ntshav ntawm Cyst/AuNPs cov khoom tuaj yeem ua tiav hauv ob kauj ruam yooj yim.

Qhov no yog qhia nyob rau hauv daim duab 1. Ua ntej, ib tug aqueous tov yog siv los yaj cov DNA fragments. Cyst/AuNPs tau muab ntxiv rau cov tshuaj tov. Ib txwm thiab malignant DNA muaj cov khoom sib txawv methylation, ua rau DNA tawg nrog cov qauv sib txawv ntawm tus kheej. Ib txwm DNA aggregates xoob thiab nws thiaj li sib sau ua ke Cyst / AuNPs, uas ua rau cov xim liab-hloov ntawm Cyst / AuNPs, yog li ntawd qhov kev hloov ntawm cov xim ntawm liab mus rau ntshav tuaj yeem pom ntawm qhov muag liab qab. Hauv qhov sib piv, qhov tshwj xeeb methylation profile ntawm qog noj ntshav DNA ua rau tsim cov pawg loj ntawm DNA tawg.

Cov duab ntawm 96-zoo daim hlau raug coj los siv lub koob yees duab smartphone. Cancer DNA tau ntsuas los ntawm lub xov tooj smartphone uas muaj kev kawm tshuab piv rau spectroscopy-based txoj kev.

Kev kuaj mob qog noj ntshav hauv cov ntshav tiag tiag

Txhawm rau txuas ntxiv kev siv hluav taws xob ntawm lub platform kev hnov ​​​​qab, cov neeg tshawb xyuas tau siv lub sensor uas ua tiav qhov sib txawv ntawm qhov qub thiab qog nqaij hlav DNA hauv cov ntshav kuaj. Cov qauv methylation ntawm CpG qhov chaw epigenetically tswj cov noob qhia. Nyob rau hauv yuav luag txhua hom mob qog noj ntshav, kev hloov pauv hauv DNA methylation thiab yog li hauv kev qhia ntawm cov noob uas txhawb cov qog nqaij hlav qog nqaij hlav tau pom los hloov.

Raws li tus qauv rau lwm cov qog nqaij hlav uas cuam tshuam nrog DNA methylation, cov kws tshawb fawb tau siv cov ntshav kuaj los ntawm cov neeg mob leukemia thiab kev tswj xyuas kev noj qab haus huv los tshawb xyuas qhov ua tau zoo ntawm thaj chaw methylation hauv kev sib txawv ntawm cov qog nqaij hlav leukaemic. Qhov no methylation toj roob hauv pes biomarker tsis tsuas yog ua tau zoo dua cov txheej txheem kuaj ntshav leukemia tam sim no, tab sis kuj qhia tau tias muaj peev xwm txuas mus rau kev tshawb pom ntxov ntawm ntau hom qog nqaij hlav siv qhov kev ntsuam xyuas yooj yim thiab ncaj nraim.

DNA los ntawm cov ntshav kuaj los ntawm 31 cov neeg mob leukemia thiab 12 tus neeg noj qab haus huv raug tshuaj xyuas. Raws li pom nyob rau hauv lub thawv zaj duab xis hauv daim duab 2a, cov txheeb ze absorbance ntawm cov qog nqaij hlav qog nqaij hlav (ΔA650/525) yog qis dua DNA los ntawm cov qauv ib txwm. Qhov no feem ntau yog vim kev txhim kho hydrophobicity ua rau ntom ntom ntawm cov qog nqaij hlav DNA, uas tiv thaiv kev sib sau ntawm Cyst / AuNPs. Yog li ntawd, cov nanoparticles no tau tawg tag nrho nyob rau hauv txheej txheej ntawm cov qog nqaij hlav cancer, uas ua rau muaj qhov sib txawv ntawm Cyst / AuNPs adsorbed ntawm ib txwm thiab mob qog noj ntshav DNA aggregates. ROC curves tau tsim los ntawm qhov sib txawv ntawm qhov pib ntawm qhov tsawg kawg nkaus ntawm ΔA650/525 mus rau qhov siab tshaj plaws.

Daim duab 2.(a) Cov txheeb ze absorbance qhov tseem ceeb ntawm cyst/AuNPs cov kev daws teeb meem uas qhia pom muaj qhov qub (xiav) thiab mob qog noj ntshav (liab) dna nyob rau hauv cov xwm txheej zoo

(DA650/525) ntawm lub thawv thawv; (b) ROC tsom xam thiab kev ntsuam xyuas ntawm kev kuaj mob. (c) Tsis meej pem matrix rau kev kuaj mob ntawm ib txwm thiab cov neeg mob qog noj ntshav. (d) rhiab heev, tshwj xeeb, tus nqi kwv yees zoo (PPV), tus nqi tsis zoo (NPV) thiab qhov tseeb ntawm txoj kev tsim.

Raws li pom nyob rau hauv daim duab 2b, cheeb tsam nyob rau hauv lub ROC nkhaus (AUC = 0.9274) tau rau lub tsim sensor pom muaj siab rhiab heev thiab tshwj xeeb. Raws li tuaj yeem pom los ntawm cov phiaj xwm lub thawv, qhov qis tshaj plaws uas sawv cev rau pawg DNA ib txwm tsis zoo sib cais los ntawm qhov siab tshaj plaws uas sawv cev rau pawg neeg mob qog noj ntshav DNA; Yog li ntawd, logistic regression tau siv los sib txawv ntawm cov pab pawg ib txwm muaj thiab mob qog noj ntshav. Muab cov txheej txheem ntawm kev ywj pheej, nws kwv yees qhov tshwm sim ntawm qhov tshwm sim, xws li mob qog noj ntshav lossis ib pab pawg. Qhov sib txawv ntawm qhov sib txawv ntawm 0 thiab 1. Qhov tshwm sim yog li qhov tshwm sim. Peb txiav txim siab qhov tshwm sim ntawm kev txheeb xyuas mob qog noj ntshav (P) raws li ΔA650/525 raws li hauv qab no.

uas b=5.3533,w1=-6.965. Rau cov qauv kev faib tawm, qhov tshwm sim tsawg dua 0.5 qhia qhov piv txwv ib txwm, thaum qhov tshwm sim ntawm 0.5 lossis siab dua qhia tias tus qauv mob qog noj ntshav. Daim duab 2c qhia txog qhov tsis meej pem matrix tsim los ntawm kev tawm-nws-ib leeg hla-validation, uas tau siv los ua kom muaj kev ruaj ntseg ntawm txoj kev faib tawm. Daim duab 2d qhia txog qhov kev ntsuam xyuas kev ntsuam xyuas ntawm txoj kev, suav nrog rhiab heev, qhov tshwj xeeb, tus nqi kwv yees zoo (PPV) thiab tus nqi tsis zoo (NPV).

Smartphone-based biosensors

Txhawm rau ua kom yooj yim rau kev sim ua piv txwv yam tsis tas siv spectrophotometers, cov kws tshawb fawb tau siv cov kev txawj ntse (AI) los txhais cov xim ntawm cov tshuaj thiab qhov txawv ntawm cov tib neeg uas muaj mob qog noj ntshav. Muab qhov no, lub zeem muag hauv computer tau siv los txhais cov xim ntawm cov tshuaj Cyst / AuNPs rau hauv ib txwm DNA (ntsuab) lossis qog nqaij hlav DNA (liab) siv cov duab ntawm 96-zoo daim hlau coj los ntawm lub koob yees duab xov tooj ntawm tes. Artificial txawj ntse tuaj yeem txo cov nqi thiab txhim kho kev nkag mus rau hauv kev txhais cov xim ntawm nanoparticle kev daws teeb meem, thiab tsis tas siv cov khoom siv kho qhov muag kho qhov muag smartphone. Thaum kawg, ob lub tshuab kev kawm, suav nrog Random Forest (RF) thiab Support Vector Machine (SVM) tau raug cob qhia los tsim cov qauv. ob qho tib si RF thiab SVM qauv raug cais cov qauv raws li qhov zoo thiab qhov tsis zoo nrog qhov tseeb ntawm 90.0%. Qhov no qhia tias kev siv cov kev txawj ntse hauv xov tooj ntawm tes-based biosensing yog qhov ua tau.

Daim duab 3.(a) Lub hom phiaj ntawm cov kev daws teeb meem tau sau tseg thaum lub sij hawm npaj cov qauv rau cov kauj ruam tau txais cov duab. (b) Cov duab piv txwv coj thaum lub sij hawm tau cov duab. (c) Xim siv ntawm cyst/AuNPs tov nyob rau hauv txhua lub qhov dej ntawm 96-zoo phaj muab rho tawm los ntawm daim duab (b).

Siv Cyst/AuNPs, cov kws tshawb fawb tau ua tiav ib qho yooj yim sensing platform rau methylation toj roob hauv pes nrhiav kom tau thiab ib tug sensor muaj peev xwm ntawm qhov txawv DNA ib txwm los ntawm cov qog nqaij hlav DNA thaum siv cov ntshav tiag tiag rau kev kuaj mob leukemia. Lub sensor tsim tau pom tias DNA rho tawm los ntawm cov ntshav kuaj tau sai thiab raug nqi kuaj xyuas me me ntawm cov qog nqaij hlav DNA (3nM) hauv cov neeg mob leukemia hauv 15 feeb, thiab pom qhov tseeb ntawm 95.3%. Txhawm rau kom yooj yim rau kev sim ua piv txwv ntxiv los ntawm kev tshem tawm qhov xav tau ntawm lub spectrophotometer, kev kawm tshuab tau siv los txhais cov xim ntawm cov tshuaj thiab kev sib txawv ntawm cov tib neeg thiab cov qog nqaij hlav uas siv cov duab hauv xov tooj, thiab qhov tseeb kuj tuaj yeem ua tiav ntawm 90.0%.

Reference: DOI: 10.1039/d2ra05725e