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Yang'anirani kayendedwe ka ma nanoparticles a magnetic iron oxide kuti mupereke cytostatics mwachindunji
Wolemba Toropova Y, Korolev D, Istomina M, Shulmeyster G, Petukhov A, Mishanin V, Gorshkov A, Podyacheva E, Gareev K, Bagrov A, Demidov O
Yana Toropova,1 Dmitry Korolev,1 Maria Istomina,1,2 Galina Shulmeyster,1 Alexey Petukhov,1,3 Vladimir Mishanin,1 Andrey Gorshkov,4 Ekaterina Podyacheva,1 Kamil Gareev,2 Alexei Bagrov,5 Oleg Demidov6,71Almazov National Medical Research Center of the Ministry of Health of the Russian Federation, St. Petersburg, 197341, Russian Federation; 2 St. Petersburg Electrotechnical University “LETI”, St. Petersburg, 197376, Russian Federation; 3 Center for Personalized Medicine, Almazov State Medical Research Center, Ministry of Health of the Russian Federation, St. Petersburg, 197341, Russia Federation; 4FSBI “Influenza Research Institute yotchedwa AA Smorodintsev” Ministry of Health of the Russian Federation, St. Petersburg, Russian Federation; 5 Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian Federation; 6 RAS Institute of Cytology, St. Petersburg, 194064, Russian Federation; 7INSERM U1231, Faculty of Medicine and Pharmacy, Bourgogne-Franche Comté University of Dijon, France Kulankhulana: Yana ToropovaAlmazov National Medical Research Centre, Ministry of Health of the Russian Federation, Saint-Petersburg, 197341, Russian Federation Tel +7 981 95264800 4997069 Imelo [email protected] Chiyambi: Njira yabwino yothetsera vuto la poizoni wa cytostatic ndikugwiritsa ntchito maginito nanoparticles (MNP) popereka mankhwala. Cholinga: Kugwiritsa ntchito mawerengedwe kuti mudziwe makhalidwe abwino a maginito omwe amalamulira MNPs mu vivo, ndikuwunika momwe maginito amaperekera MNPs ku zotupa za mbewa mu vitro ndi mu vivo. (MNPs-ICG) imagwiritsidwa ntchito. Kafukufuku wa mphamvu ya kuwala mu vivo adachitika m'mbewa zotupa, zokhala ndi mphamvu ya maginito komanso zopanda pamalo omwe akufuna. Maphunziro awa adachitika pa scaffold ya hydrodynamic yomwe idapangidwa ndi Institute of Experimental Medicine ya Almazov State Medical Research Center ya Unduna wa Zaumoyo ku Russia. Zotsatira zake: Kugwiritsa ntchito maginito a neodymium kunathandizira kusonkhanitsa kwa MNP mosankha. Mphindi imodzi pambuyo popereka MNPs-ICG kwa mbewa zokhala ndi chotupa, MNPs-ICG imasonkhana kwambiri m'chiwindi. Ngati palibe mphamvu yamaginito, izi zikusonyeza njira yake yogwiritsira ntchito kagayidwe kachakudya. Ngakhale kuti kuwonjezeka kwa kuwala kwa chotupacho kunawonedwa pamaso pa mphamvu yamaginito, mphamvu ya kuwala kwa fluorescence m'chiwindi cha nyamayo sinasinthe pakapita nthawi. Kutsiliza: Mtundu uwu wa MNP, kuphatikiza ndi mphamvu yamaginito yowerengedwa, ukhoza kukhala maziko a chitukuko cha kutumiza mankhwala opangidwa ndi maginito ku minofu ya chotupa. Mawu Ofunika: kusanthula kwa fluorescence, indocyanine, nanoparticles ya iron oxide, kupereka kwa magnetron kwa cytostatics, kuyang'anira chotupa.
Matenda a chotupa ndi chimodzi mwa zifukwa zazikulu zomwe zimayambitsa imfa padziko lonse lapansi. Nthawi yomweyo, kuchuluka kwa matenda ndi imfa za matenda a chotupa kulipobe. 1 Mankhwala a chemotherapy omwe amagwiritsidwa ntchito masiku ano akadali amodzi mwa mankhwala akuluakulu a zotupa zosiyanasiyana. Nthawi yomweyo, kupanga njira zochepetsera poizoni wa cytostatics ndikofunikirabe. Njira yodalirika yothetsera vuto lake la poizoni ndikugwiritsa ntchito zonyamula mankhwala a nano-scale kuti zigwirizane ndi njira zoperekera mankhwala, zomwe zingapereke kuchuluka kwa mankhwala m'thupi la chotupa popanda kuwonjezera kuchuluka kwawo m'ziwalo ndi minofu yathanzi. 2 Njirayi imapangitsa kuti zikhale zotheka kukonza magwiridwe antchito ndi kuyang'ana kwa mankhwala a chemotherapy pa minofu ya chotupa, pomwe kuchepetsa poizoni wawo m'thupi.
Pakati pa tinthu tating'onoting'ono tomwe timaganiziridwa kuti tipereke mankhwala oletsa kutupa, tinthu tating'onoting'ono tomwe timapangidwa ndi maginito (MNPs) ndi tofunika kwambiri chifukwa cha mankhwala awo apadera, zamoyo, komanso maginito, zomwe zimaonetsetsa kuti zimagwira ntchito zosiyanasiyana. Chifukwa chake, tinthu tating'onoting'ono tomwe timapangidwa ndi maginito tingagwiritsidwe ntchito ngati njira yotenthetsera pochiza zotupa ndi hyperthermia (magnetic hyperthermia). Tingagwiritsidwenso ntchito ngati njira zodziwira matenda (magnetic resonance diagnosis). 3-5 Pogwiritsa ntchito makhalidwe amenewa, kuphatikiza kuthekera kwa MNP kusonkhana m'dera linalake, pogwiritsa ntchito mphamvu yamagetsi yakunja, kupereka mankhwala okonzedwa kumatsegula kupangidwa kwa njira ya magnetron yogwira ntchito zambiri kuti ilowetse ma cytostatics kumalo a chotupa. Dongosolo lotere likuphatikizapo MNP ndi maginito kuti azilamulira kayendedwe kawo m'thupi. Pankhaniyi, mphamvu yamagetsi yakunja ndi maginito omwe amaikidwa m'thupi lomwe lili ndi chotupacho angagwiritsidwe ntchito ngati gwero la mphamvu yamagetsi. 6 Njira yoyamba ili ndi zofooka zazikulu, kuphatikizapo kufunika kogwiritsa ntchito zida zapadera zowunikira mankhwala ndi maginito komanso kufunika kophunzitsa ogwira ntchito kuti achite opaleshoni. Kuphatikiza apo, njira iyi ndi yocheperako chifukwa cha mtengo wokwera ndipo ndi yoyenera kokha pa zotupa "zakunja" zomwe zili pafupi ndi pamwamba pa thupi. Njira ina yogwiritsira ntchito ma implants a maginito imakulitsa kuchuluka kwa kugwiritsa ntchito ukadaulo uwu, zomwe zimapangitsa kuti ugwiritsidwe ntchito pa zotupa zomwe zili m'malo osiyanasiyana a thupi. Maginito ndi maginito onse omwe amaphatikizidwa mu stent yamkati angagwiritsidwe ntchito ngati ma implants owononga chotupa m'ziwalo zopanda kanthu kuti zitsimikizire kuti zili bwino. Komabe, malinga ndi kafukufuku wathu wosasindikizidwa, izi sizokwanira kuti zitsimikizire kuti MNP imasungidwa m'magazi.
Kugwira ntchito bwino kwa mankhwala a magnetron kumadalira zinthu zambiri: makhalidwe a chonyamulira maginito chokha, ndi makhalidwe a gwero la mphamvu ya maginito (kuphatikizapo magawo a geometric a maginito okhazikika ndi mphamvu ya mphamvu ya maginito yomwe amapanga). Kupanga ukadaulo wopambana wotsogolera maselo oletsa maginito kuyenera kuphatikizapo kupanga zonyamulira mankhwala zoyenera za nanoscale zamaginito, kuwunika chitetezo chawo, ndikupanga njira yowonera yomwe imalola kutsatira mayendedwe awo m'thupi.
Mu kafukufukuyu, tinawerengera mwa masamu makhalidwe abwino kwambiri a mphamvu ya maginito kuti tiwongolere chonyamulira mankhwala cha nano-scale m'thupi. Kuthekera kosunga MNP kudzera mu khoma la mitsempha yamagazi mothandizidwa ndi mphamvu ya maginito yomwe imagwiritsidwa ntchito yokhala ndi makhalidwe awa a makompyuta kunaphunziridwanso m'mitsempha yamagazi ya makoswe okhaokha. Kuphatikiza apo, tinapanga ma conjugates a MNPs ndi ma fluorescent agents ndikupanga njira yowonetsera mawonekedwe awo m'thupi. Pansi pa mikhalidwe ya m'thupi, m'makoswe a mtundu wa chotupa, mphamvu yosonkhanitsa ya MNPs m'maselo a chotupa ikaperekedwa m'thupi mothandizidwa ndi mphamvu ya mphamvu ya maginito inaphunziridwa.
Mu kafukufuku wa in vitro, tinagwiritsa ntchito MNP yotchulidwa, ndipo mu kafukufuku wa in vivo, tinagwiritsa ntchito MNP yokutidwa ndi lactic acid polyester (polylactic acid, PLA) yokhala ndi fluorescent agent (indolecyanine; ICG). MNP-ICG ikuphatikizidwa mu Nkhaniyi, gwiritsani ntchito (MNP-PLA-EDA-ICG).
Kapangidwe ndi kapangidwe ka thupi ndi mankhwala a MNP zafotokozedwa mwatsatanetsatane kwina.
Pofuna kupanga MNPs-ICG, ma conjugates a PLA-ICG adapangidwa koyamba. Chisakanizo cha ufa cha racemic cha PLA-D ndi PLA-L chokhala ndi kulemera kwa molekyulu ya 60 kDa chinagwiritsidwa ntchito.
Popeza PLA ndi ICG zonse ndi ma asidi, kuti apange ma conjugates a PLA-ICG, choyamba muyenera kupanga amino-terminated spacer pa PLA, yomwe imathandiza ICG chemisorb kupita ku spacer. Spacer idapangidwa pogwiritsa ntchito ethylene diamine (EDA), njira ya carbodiimide ndi water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC). PLA-EDA spacer imapangidwa motere. Onjezani molar excess ya EDA ka 20-fold ndi molar excess ya EDAC ka 20-fold ku 2 mL ya 0.1 g/mL PLA chloroform solution. Kupanga kunachitika mu chubu choyesera cha polypropylene cha 15 mL pa shaker pa liwiro la mphindi 300-1 kwa maola awiri. Kupanga kukuwonetsedwa mu Chithunzi 1. Bwerezani kupanga ndi ma reagents ochulukirapo ka 200 kuti muwongolere kupanga kuphatikizika.
Kumapeto kwa kupanga, yankholo linayikidwa mu centrifuge pa liwiro la 3000 min-1 kwa mphindi 5 kuti lichotse zinthu zochulukirapo za polyethylene. Kenako, 2 mL ya yankho la 0.5 mg/mL ICG mu dimethyl sulfoxide (DMSO) inawonjezedwa ku yankho la 2 mL. Choyambitsa chimakhazikika pa liwiro loyambitsa la 300 min-1 kwa maola awiri. Chithunzi cha schematic cha conjugate yomwe yapezeka chikuwonetsedwa mu Chithunzi 2.
Mu 200 mg MNP, tinawonjezera 4 mL PLA-EDA-ICG conjugate. Gwiritsani ntchito LS-220 shaker (LOIP, Russia) kuti musonkhezere suspension kwa mphindi 30 pafupipafupi kwa mphindi 300-1. Kenako, idatsukidwa ndi isopropanol katatu ndikuyikidwa mu magnetic separation. Gwiritsani ntchito UZD-2 Ultrasonic Disperser (FSUE NII TVCH, Russia) kuti muwonjezere IPA ku suspension kwa mphindi 5-10 pansi pa ultrasound action mosalekeza. Pambuyo pa kutsuka kwachitatu kwa IPA, precipitate idatsukidwa ndi madzi osungunuka ndikuyiyikanso mu physiological saline pamlingo wa 2 mg/mL.
Zipangizo za ZetaSizer Ultra (Malvern Instruments, UK) zinagwiritsidwa ntchito pophunzira kukula kwa MNP yomwe yapezeka mu yankho lamadzi. Maikolosikopu ya ma electron otumizira (TEM) yokhala ndi JEM-1400 STEM field emission cathode (JEOL, Japan) inagwiritsidwa ntchito pophunzira mawonekedwe ndi kukula kwa MNP.
Mu phunziroli, timagwiritsa ntchito maginito okhazikika a cylindrical (N35 grade; okhala ndi nickel protective coating) ndi kukula kotsatiraku (kutalika kwa mzere wautali × m'mimba mwake wa silinda): 0.5×2 mm, 2×2 mm, 3×2 mm ndi 5×2 mm.
Kafukufuku wa in vitro wa kayendedwe ka MNP mu dongosolo la chitsanzo adachitika pa scaffold ya hydrodynamic yomwe idapangidwa ndi Institute of Experimental Medicine ya Almazov State Medical Research Center ya Russian Ministry of Health. Kuchuluka kwa madzi ozungulira (madzi osungunuka kapena yankho la Krebs-Henseleit) ndi 225 mL. Maginito a cylindrical okhala ndi maginito a axially amagwiritsidwa ntchito ngati maginito okhazikika. Ikani maginito pa chogwirira 1.5 mm kutali ndi khoma lamkati la chubu chapakati chagalasi, ndipo kumapeto kwake kuyang'ana mbali ya chubu (choyima). Kuthamanga kwa madzi mu kuzungulira kotsekedwa ndi 60 L/h (kofanana ndi liwiro la mzere wa 0.225 m/s). Njira ya Krebs-Henseleit imagwiritsidwa ntchito ngati madzi ozungulira chifukwa ndi analog ya plasma. Mphamvu ya dynamic viscosity coefficient ya plasma ndi 1.1–1.3 mPa∙s. 9 Kuchuluka kwa MNP komwe kumamatiridwa mu mphamvu ya maginito kumatsimikiziridwa ndi spectrophotometry kuchokera ku kuchuluka kwa chitsulo mumadzi ozungulira pambuyo pa kuyesa.
Kuphatikiza apo, maphunziro oyesera achitika patebulo labwino kwambiri la makina amadzimadzi kuti adziwe momwe mitsempha yamagazi imayendera. Zigawo zazikulu za hydrodynamic support zikuwonetsedwa pa Chithunzi 3. Zigawo zazikulu za hydrodynamic stent ndi kuzungulira kotsekedwa komwe kumatsanzira gawo lodutsa la dongosolo la mitsempha yamagazi ndi thanki yosungiramo zinthu. Kuyenda kwa madzi a chitsanzocho motsatira mzere wa gawo la mitsempha yamagazi kumaperekedwa ndi pampu ya peristaltic. Pa nthawi yoyesera, sungani nthunzi ndi kutentha komwe kukufunika, ndikuyang'anira magawo a dongosolo (kutentha, kuthamanga, kuchuluka kwa madzi, ndi pH).
Chithunzi 3 Chithunzi cha block cha momwe amagwiritsidwira ntchito pophunzira momwe khoma la mtsempha wa carotid limalowera. 1-thanki yosungiramo zinthu, 2-peristaltic pump, 3-njira yolowera suspension yokhala ndi MNP mu loop, 4-flow meter, 5-pressure sensor mu loop, 6-heat exchanger, 7-chamber yokhala ndi chidebe, 8-gwero la mphamvu ya maginito, 9-baluni yokhala ndi ma hydrocarbons.
Chipinda chokhala ndi chidebecho chili ndi zidebe zitatu: chidebe chachikulu chakunja ndi zidebe ziwiri zazing'ono, zomwe manja a dera lapakati amadutsa. Cannula imayikidwa mu chidebe chaching'ono, chidebecho chimamangiriridwa pa chidebe chaching'ono, ndipo nsonga ya cannula imamangidwa mwamphamvu ndi waya woonda. Malo pakati pa chidebe chachikulu ndi chidebe chaching'ono amadzazidwa ndi madzi osungunuka, ndipo kutentha kumakhalabe kosalekeza chifukwa cholumikizidwa ndi chosinthira kutentha. Malo omwe ali mu chidebe chaching'ono amadzazidwa ndi yankho la Krebs-Henseleit kuti maselo amitsempha yamagazi azikhala olimba. Tankiyo imadzazidwanso ndi yankho la Krebs-Henseleit. Dongosolo loperekera mpweya (carbon) limagwiritsidwa ntchito kutenthetsa yankho mu chidebe chaching'ono mu thanki yosungiramo ndi chipinda chomwe chili ndi chidebecho (Chithunzi 4).
Chithunzi 4 Chipinda chomwe chidebecho chimayikidwa. 1-Kannula yochepetsera mitsempha yamagazi, 2-Chipinda chakunja, 3-Chipinda chaching'ono. Muvi umasonyeza komwe madzi a chitsanzocho akupita.
Kuti adziwe kuchuluka kwa madzi m'mitsempha yamagazi, mtsempha wa carotid wa makoswe unagwiritsidwa ntchito.
Kulowetsedwa kwa MNP suspension (0.5mL) mu dongosololi kuli ndi makhalidwe awa: voliyumu yonse yamkati mwa thanki ndi chitoliro cholumikizira mu kuzungulira ndi 20mL, ndipo voliyumu yamkati ya chipinda chilichonse ndi 120mL. Gwero lakunja la maginito ndi maginito okhazikika okhala ndi kukula kokhazikika kwa 2×3 mm. Imayikidwa pamwamba pa chipinda chimodzi chaching'ono, 1 cm kutali ndi chidebe, ndipo mbali imodzi ikuyang'ana khoma la chidebe. Kutentha kumasungidwa pa 37°C. Mphamvu ya pampu yozungulira imayikidwa pa 50%, yomwe ikugwirizana ndi liwiro la 17 cm/s. Monga chowongolera, zitsanzo zinatengedwa mu selo yopanda maginito okhazikika.
Ola limodzi pambuyo popereka kuchuluka kwa MNP, chitsanzo chamadzimadzi chinatengedwa kuchokera mchipindamo. Kuchuluka kwa tinthu tating'onoting'ono kunayesedwa ndi spectrophotometer pogwiritsa ntchito Unico 2802S UV-Vis spectrophotometer (United Products & Instruments, USA). Poganizira kuchuluka kwa kuyamwa kwa MNP suspension, muyeso unachitidwa pa 450 nm.
Malinga ndi malangizo a Rus-LASA-FELASA, nyama zonse zimaleredwa ndi kukwezedwa m'malo enaake opanda tizilombo toyambitsa matenda. Kafukufukuyu akutsatira malamulo onse oyenera okhudza makhalidwe abwino okhudzana ndi kuyesa ndi kufufuza nyama, ndipo wavomerezedwa ndi Almazov National Medical Research Center (IACUC). Nyamazo zimamwa madzi nthawi zonse komanso zimadyetsedwa nthawi zonse.
Kafukufukuyu adachitika pa mbewa 10 za amuna za masabata 12 zomwe zidapatsidwa mankhwala oletsa kutupa (NOD.Cg-Prkdcscid Il2rgtm1Wjl/Szj, Jackson Laboratory, USA) 10, zolemera 22 g ± 10%. Popeza chitetezo cha mbewa zofooka chachepetsedwa, mbewa zofooka za mbewa za mzere uwu zimalola kuikidwa kwa maselo ndi minofu ya anthu popanda kukanidwa kuikidwa kwa ena. Zinyama zochokera m'mabokosi osiyanasiyana zidapatsidwa mwachisawawa ku gulu loyesera, ndipo zidaleredwa limodzi kapena kuyikidwa mwadongosolo ku mabedi a magulu ena kuti zitsimikizire kuti zikupezeka mofanana ndi tizilombo toyambitsa matenda.
Mzere wa maselo a khansa ya anthu a HeLa umagwiritsidwa ntchito kukhazikitsa chitsanzo cha xenograft. Maselowa adalimidwa mu DMEM yokhala ndi glutamine (PanEco, Russia), yowonjezerapo 10% fetal bovine serum (Hyclone, USA), 100 CFU/mL penicillin, ndi 100 μg/mL streptomycin. Mzere wa maselowo unaperekedwa mokoma mtima ndi Gene Expression Regulation Laboratory ya Institute of Cell Research ya Russian Academy of Sciences. Asanapereke jekeseni, maselo a HeLa adachotsedwa mu pulasitiki yolimidwa ndi yankho la 1:1 trypsin:Versene (Biolot, Russia). Pambuyo potsuka, maselowo adayimitsidwa m'malo okwana maselo 5×106 pa 200 μL, ndikuchepetsedwa ndi basement membrane matrix (LDEV-FREE, MATRIGEL® CORNING®) (1:1, pa ayezi). Kuyimitsidwa kwa maselo kokonzedwako kunabayidwa pansi pa khungu la ntchafu ya mbewa. Gwiritsani ntchito ma caliper amagetsi kuti muwone kukula kwa chotupa masiku atatu aliwonse.
Chotupacho chitafika pa 500 mm3, maginito okhazikika adayikidwa mu minofu ya nyama yoyesera pafupi ndi chotupacho. Mu gulu loyesera (MNPs-ICG + tumor-M), 0.1 mL ya MNP suspension idabayidwa ndikuwonetsedwa ku mphamvu ya maginito. Nyama zonse zomwe sizinachiritsidwe zidagwiritsidwa ntchito ngati zowongolera (kumbuyo). Kuphatikiza apo, nyama zomwe zidabayidwa ndi 0.1 mL ya MNP koma sizinayikidwe ndi maginito (MNPs-ICG + tumor-BM) zidagwiritsidwa ntchito.
Kuwonetsa kuwala kwa zitsanzo za in vivo ndi in vitro kunachitika pa IVIS Lumina LT series III bioimager (PerkinElmer Inc., USA). Pakuwonetsa mu vitro, voliyumu ya 1 mL ya synthetic PLA-EDA-ICG ndi MNP-PLA-EDA-ICG conjugate idawonjezedwa ku zitsime za mbale. Poganizira za mawonekedwe a kuwala kwa utoto wa ICG, fyuluta yabwino kwambiri yogwiritsidwa ntchito kudziwa mphamvu yowala ya chitsanzocho imasankhidwa: kutalika kwakukulu kwa kutalika kwa kuwala ndi 745 nm, ndipo kutalika kwa kutalika kwa kuwala ndi 815 nm. Pulogalamu ya Living Image 4.5.5 (PerkinElmer Inc.) idagwiritsidwa ntchito poyesa kuchuluka kwa mphamvu ya kuwala kwa zitsime zomwe zili ndi conjugate.
Kuchuluka kwa kuwala ndi kuchuluka kwa conjugate ya MNP-PLA-EDA-ICG kunayesedwa mu mbewa za mtundu wa chotupa cha m'thupi, popanda kukhalapo ndi kugwiritsa ntchito mphamvu ya maginito pamalo omwe akufuna. Mbewa zinapatsidwa mankhwala oletsa ululu ndi isoflurane, kenako 0.1 mL ya conjugate ya MNP-PLA-EDA-ICG inabayidwa kudzera m'mitsempha ya mchira. Mbewa zomwe sizinalandire chithandizo zinagwiritsidwa ntchito ngati chowongolera choipa kuti zipeze maziko a kuwala. Mukapereka conjugate kudzera m'mitsempha, ikani nyamayo pamalo otentha (37°C) m'chipinda cha IVIS Lumina LT series III fluorescence imager (PerkinElmer Inc.) pamene mukupuma ndi 2% isoflurane anaesthetization. Gwiritsani ntchito fyuluta yomangidwa mkati ya ICG (745–815 nm) kuti muzindikire chizindikiro mphindi imodzi ndi mphindi 15 mutayambitsa MNP.
Kuti aone kuchuluka kwa conjugate mu chotupacho, dera la peritoneal la nyamayo linaphimbidwa ndi pepala, zomwe zinathandiza kuchotsa kuwala kowala komwe kumakhudzana ndi kuchuluka kwa tinthu m'chiwindi. Pambuyo pophunzira za kufalikira kwa MNP-PLA-EDA-ICG, nyamazo zinaphedwa mwachibadwa mwa kupatsidwa mankhwala oletsa ululu a isoflurane kuti alekanitse madera a chotupa ndikuwunika kuchuluka kwa kuwala kwa kuwala. Gwiritsani ntchito pulogalamu ya Living Image 4.5.5 (PerkinElmer Inc.) kuti mugwiritse ntchito kusanthula kwa chizindikiro kuchokera kudera losankhidwa. Miyeso itatu inatengedwa pa nyama iliyonse (n = 9).
Mu kafukufukuyu, sitinawerenge kuchuluka kwa ICG yomwe yayenda bwino pa MNPs-ICG. Kuphatikiza apo, sitinayerekezere momwe nanoparticles imagwirira ntchito pogwiritsa ntchito maginito okhazikika amitundu yosiyanasiyana amagwirira ntchito. Kuphatikiza apo, sitinayang'ane momwe mphamvu ya maginito imakhudzira kusungidwa kwa nanoparticles m'maselo a chotupa kwa nthawi yayitali.
Ma nanoparticles ndi ochulukirapo, ndi kukula kwapakati pa 195.4 nm. Kuphatikiza apo, kuyimitsidwako kunali ndi ma agglomerates okhala ndi kukula kwapakati pa 1176.0 nm (Chithunzi 5A). Pambuyo pake, gawolo linasefedwa kudzera mu fyuluta ya centrifugal. Mphamvu ya zeta ya tinthu tating'onoting'ono ndi -15.69 mV (Chithunzi 5B).
Chithunzi 5 Makhalidwe enieni a kuyimitsidwa: (A) kugawa kwa tinthu tating'onoting'ono; (B) kugawa kwa tinthu tating'onoting'ono pa zeta potential; (C) Chithunzi cha TEM cha tinthu tating'onoting'ono tating'onoting'ono.
Kukula kwa tinthu tating'onoting'ono kwenikweni ndi 200 nm (Chithunzi 5C), chopangidwa ndi MNP imodzi yokhala ndi kukula kwa 20 nm, ndi chipolopolo cha PLA-EDA-ICG cholumikizidwa ndi organic chokhala ndi kuchuluka kochepa kwa ma electron. Kupangidwa kwa ma agglomerate mu mayankho amadzi kumatha kufotokozedwa ndi modulus yotsika ya mphamvu ya electromotive ya nanoparticles imodzi.
Pa maginito okhazikika, pamene maginito akhazikika mu voliyumu V, mawu ofunikira amagawidwa m'magulu awiri, omwe ndi voliyumu ndi pamwamba:
Pankhani ya chitsanzo chokhala ndi maginito osasintha, kuchuluka kwa mphamvu yamagetsi ndi zero. Kenako, mawonekedwe a vekitala yopangira maginito adzakhala motere:
Gwiritsani ntchito pulogalamu ya MATLAB (MathWorks, Inc., USA) powerengera manambala, nambala ya layisensi ya maphunziro ya ETU "LETI" 40502181.
Monga momwe zasonyezedwera pa Chithunzi 7 Chithunzi 8 Chithunzi 9 Chithunzi-10, mphamvu ya maginito yamphamvu kwambiri imapangidwa ndi maginito yolunjika ku axial kuchokera kumapeto kwa silinda. Utali wothandiza wa ntchito ndi wofanana ndi geometry ya maginito. Mu maginito ozungulira okhala ndi silinda yomwe kutalika kwake kuli kwakukulu kuposa m'mimba mwake, mphamvu ya maginito yamphamvu kwambiri imawonekera mu axial-radial direction (ya gawo lofanana); chifukwa chake, ma silinda awiri okhala ndi aspect ratio yayikulu (m'mimba mwake ndi kutalika) MNP adsorption ndiye yothandiza kwambiri.
Chithunzi 7 Gawo la mphamvu ya maginito yolowetsa mphamvu Bz motsatira mzere wa Oz wa maginito; kukula koyenera kwa maginito: mzere wakuda 0.5×2mm, mzere wabuluu 2×2mm, mzere wobiriwira 3×2mm, mzere wofiira 5×2mm.
Chithunzi 8 Gawo la maginito loyambitsa Br lili molunjika ku mzere wa maginito Oz; kukula koyenera kwa maginito: mzere wakuda 0.5×2mm, mzere wabuluu 2×2mm, mzere wobiriwira 3×2mm, mzere wofiira 5×2mm.
Chithunzi 9 Gawo la Bz la mphamvu ya maginito pa mtunda wa r kuchokera kumapeto kwa mzere wa maginito (z=0); kukula koyenera kwa maginito: mzere wakuda 0.5×2mm, mzere wabuluu 2×2mm, mzere wobiriwira 3×2mm, mzere wofiira 5×2mm.
Chithunzi 10 Gawo la maginito lolowera mbali imodzi; kukula kwa maginito wamba: mzere wakuda 0.5×2mm, mzere wabuluu 2×2mm, mzere wobiriwira 3×2mm, mzere wofiira 5×2mm.
Ma hydrodynamic models apadera angagwiritsidwe ntchito pophunzira njira yoperekera MNP ku minofu ya chotupa, kuyika tinthu tating'onoting'ono m'dera lomwe likufunidwa, ndikuzindikira momwe tinthu tating'onoting'ono timagwirira ntchito pansi pa mikhalidwe ya hydrodynamic mu dongosolo la magazi. Maginito okhazikika angagwiritsidwe ntchito ngati maginito akunja. Ngati tinyalanyaza kuyanjana kwa magnetostatic pakati pa tinthu tating'onoting'ono ndipo sitiganizira chitsanzo cha magnetic fluid, ndikokwanira kuyerekeza kuyanjana pakati pa maginito ndi tinthu tating'onoting'ono tomwe tili ndi dipole-dipole approximation.
Pamene m ndi mphindi ya maginito ya maginito, r ndi vekitala yozungulira ya malo omwe nanoparticle ili, ndipo k ndi chinthu cha dongosolo. Mu dipole approximation, gawo la maginito lili ndi mawonekedwe ofanana (Chithunzi 11).
Mu mphamvu ya maginito yofanana, tinthu tating'onoting'ono timangozungulira motsatira mizere ya mphamvu. Mu mphamvu ya maginito yosakhala yofanana, mphamvu imagwira ntchito pa iyo:
Kodi chochokera ku malangizo operekedwa l chili kuti? Kuphatikiza apo, mphamvuyo imakoka tinthu tating'onoting'ono m'malo osafanana kwambiri a munda, ndiko kuti, kupindika ndi kuchuluka kwa mizere ya mphamvu kumawonjezeka.
Chifukwa chake, ndikofunikira kugwiritsa ntchito maginito amphamvu mokwanira (kapena unyolo wa maginito) wokhala ndi anisotropy yodziwikiratu m'dera lomwe tinthu timeneti tili.
Gome 1 likuwonetsa kuthekera kwa maginito amodzi ngati gwero lokwanira la maginito kuti ligwire ndikusunga MNP mu bedi la mitsempha ya munda wogwiritsidwa ntchito.