Search

Nanomaterials designed for drug delivery applications require important properties that include monodispersity, biocompatibility, long circulation time which are dependent on size, shape, composition, surface charge among others. Incorporation of targeting and imaging modalities into such nanomaterials allows for both therapeutic and diagnostic functions. Au nanoparticles (NPs), besides being biocompatible, are known to show remarkable optical properties, widely exploited for both bio-sensing and imaging. Setting in of anisotropy causes a wider frequency response range in terms of plasmonic properties, making them promising candidates for hyperthermia. On the other hand, Fe NPs display superparamagnetic properties that can be used for targeting as well as imaging based on magnetic resonance. Another field of nanomaterials that has garnered interest in recent times is stimuli sensitive hydrogels that swell and collapse in response to temperature and/or pH. These entropically driven volumetric transitions enable release of the cargo as a function of changing stimuli, making them promising candidates for controlled release. Combination of nanomaterials leads to synergistic enhancement of properties stemming from their respective counterparts. Core-shell NPs is one such combination that has been studied in this work. The main focus of this thesis has been to synthesize, characterize and functionalize core-shell NPs with an aim to use these nanomaterials for theranostic (therapeutic and diagnostic combined) applications. In this pursuit, core-shell Fe@Au NPs, anisotropic Au NPs, poly(N-isopropylacrylamide) (pNIPAM) based hydrogels and hybrid NPs formed by combination of metallic NPs and hydrogels have been studied. The physico-chemical properties of these NPs have been mapped using a wide array of characterization techniques. Size measurements have been done using dynamic light scattering (DLS) and scanning transmission electron microscopy S(T)EM. The plasmonic properties of Au have been characterized primarily using UV-Vis spectroscopy while surface properties of the NPs have been tracked using electrophoretic mobility measurements, X-ray photoelectron spectroscopy (XPS) among other techniques. Different hybrid NPs have been loaded with model protein drug Cytochrome-C or L-Dopa, a drug administered for Parkinson’s disease, in order to understand the effects of size, shape, particle number density, drug-carrier interaction, response to stimuli on both loading and release. Release kinetics have been modelled in order to understand the conformational changes in the NPs leading to effective release of the drug. Fe@Au NPs have been shown to have negligible cytotoxic effects on different cell lines, in addition to their remarkable magnetic and optical properties. In order to further modify the optical properties, anisotropic Au NPs have been synthesized to understand their growth mechanisms. Five differently shaped Au NPs have been thereafter functionalized to assess their cytotoxicity on cancer cells and also to understand the role of shape in the release kinetics of a model protein drug. One of the main findings from the thesis work is that incorporation of metallic NPs inside temperature and/or pH sensitive hydrogels enhances drug loading capacities. In addition, the loaded drug is squeezed out at a faster rate from these systems when the hydrogel units collapse above volume phase transition temperature (VPTT). The swellingcollapse properties of the hydrogels have been captured using a robust methodology developed for the determination of VPTT. A predictive reversibility parameter has been defined for the first time taking all the system state points into consideration. Thus, the NPs studied within the scope of this work provide an incremental contribution to the ever expanding search for smart materials for drug delivery applications.

The master thesis has investigated primarily on the synthesis of different polymeric NPs viz PLA (synthesized in house as well as commercial grade), PLGA (commercial) and PCL(synthesized in house, having different functionalities ?COOH, -PEG and their blends) employing flash nano-precipitation technique in a multi inlet vortex mixer (MIVM), previously optimized in the Morbidelli group at ETH. These NPs were characterized using DLS (Dynamic Light Scattering) and Zeta-Sizer to report the variation of the sizes and zeta potentials respectively of the NPs as a function of polymer molecular weight and initial concentration of polymer. The lowest possible sizes of the NPs were then selected for further studies as the overall motivation of the work is to synthesize NCs composed of primary particles and thereafter compare and contrast drug loading, encapsulation efficiencies and release kinetics of a model drug between the two. Ibuprofen (model drug) was loaded into the primary NPs using the MIVM setup, following which drug loading and encapsulation efficiencies were measured using High Performance Liquid Chromatography (HPLC). The release kinetics experiments were performed at 37°C and also studied at room temperature (25°C) and 45°C to evaluate the effect of temperature on release mechanism. The drug-loaded NPs were separated from the free drug in solution at different times using centrifugal filtration. The amount of drug released over time was measured by analyzing these supernatants using HPLC. The MIVM setup is found to produce stable polymeric NPs as small as 50nm and as large as 155nm depending on polymer concentration and nature of polymer. The results indicate that this setup is capable of producing drug loaded NPs with high drug loading efficiencies varying between 75% and 88% differing with polymers. This particular aspect has been established to be both reproducible and valid for a wide range of polymers through subsequent experiments. On the contrary, the release kinetics from almost all the different types of polymeric systems is slow; lasting over several days and moreover, it is not possible to release the entire loaded drug. It is claimed that either the chemical interaction of the polymers with ibuprofen or the location of the drug inside the polymeric NPs is the potential reason for extremely slow release kinetics. It is therefore suggested that further investigation is needed for the same system with another drug, having similar solubility parameters as ibuprofen to confirm the observed behaviour or even a completely different synthesis method for drug loaded polymeric NPs using ibuprofen to substantiate the observed results.

Den voksende elbilsindustrien og den tilknyttede økningen i etterspørselen etter litium-ion-batterier (LIB) har resultert i en betydelig økning i batteriavfall. Nåværende resirkuleringskapasitet strever med å holde tritt med dette økende avfallet, og effektiv litiumgjenvinning forblir en utfordring i kommersielle gjenvinningsanlegg. Denne bacheloroppgaven gir en omfattende oversikt og analyse av eksisterende metoder og hindringer knyttet til litiumgjenvinning fra litium-ion-batteriavfall fra elbiler. Hovedmålene er å vurdere effektiviteten, miljøpåvirkningen og økonomisk gjennomførbarhet av ulike gjenvinningsmetoder, samt å identifisere nøkkelutfordringer og muligheter for forbedring. Gjennomgangen fokuserer på tre hovedteknikker for litiumgjenvinning: pyrometallurgiske, hydrometallurgiske og direkte gjenvinningsprosesser. Funnene indikerer at selv om pyrometallurgiske prosesser er mye brukt, har de høyt energiforbruk og betydelige miljømessige bekymringer. I motsetning til dette viser hydrometallurgiske prosesser større litiumgjenvinningsrater og redusert miljøpåvirkning, men krever omfattende forbehandlingsprosedyrer. Direkte gjenvinningsmetoder, som fortsatt er i utviklingsstadiene, har potensiale til å håndtere ulempene med de andre teknikkene, men sliter med utfordringer knyttet til batteridesign og lavverdig produkt. Denne gjennomgangen understreker behovet for mer bærekraftige og effektive litiumgjenvinningsprosesser og understreker behovet for å takle teknologiske og regulatoriske hindringer for å fremme en sirkulær økonomi i EV-batterisektoren. The burgeoning electric vehicle (EV) industry and the consequent surge in demand for lithium-ion batteries (LIBs) have resulted in a substantial increase in battery waste. Current recycling capacity struggles to keep pace with this mounting waste, and effective lithium recovery remains a challenge in commercial plants. This bachelor thesis provides a comprehensive overview and analysis of existing methods and obstacles associated with lithium recovery from lithium-ion EV battery waste. The primary objectives are to assess the efficiency, environmental impact, and economic feasibility of various recovery methods, as well as to pinpoint key challenges and opportunities for enhancement. The review focuses on three principal lithium recovery techniques: pyrometallurgical, hydrometallurgical, and direct recycling processes. The findings indicate that while pyrometallurgical processes are widely employed, they exhibit high energy consumption and significant environmental concerns. In contrast, hydrometallurgical processes demonstrate greater lithium recovery rates and reduced environmental impact but necessitate extensive pre-treatment procedures. Direct recycling methods, still in developmental stages, hold the potential to address drawbacks of the other techniques but grapple with challenges concerning battery design and low-grade product. This review underscores the imperative for more sustainable and efficient lithium recovery processes and stresses the need to tackle technological and regulatory hurdles to foster a circular economy in the EV battery sector.

Nanomaterialer er materialer med minst én dimensjon i milliarddelen av en meters rekkevidde (10-9 m). Betydelig forskning har blitt utført de siste to tiårene på utvikling og utvikling av magnetiske nanopartikler. Magnetiske partikler gir ekstremt effektive energiinnsamlingssystemer som har potensial til å revolusjonere dagens behandlings- og diagnostiske prosedyrer. Den spesifikke naturen til overflatebelegget er avgjørende siden det kan påvirke viktige IONP-funksjoner som kolloidal stabilitet, toksisitet, magnetisme og merkingseffektivitet. Polymerer brukes ofte som IONP-belegg fordi de kan forbedre kolloidal stabilitet under hydrofile forhold og bevare jernoksidkjernen fra nedbrytning. I denne studien ble kitosan brukt til å belegge IONP-er ved bruk av nanoutfellingsmetode. Dette prosjektet ble delt inn i tre faser. Bare kitosan NPs-syntese, IONPs-syntese og til slutt kitosanbelagt IONPs-syntese. Størrelsen, overflateladningen, molekylær strukturanalyse og magnetiske egenskaper (bare IONP-er) ble karakterisert av disse partiklene. Foreløpig studie ble også gjort ved å syntetisere PLGA NP-er og PLGA-IONP-er. Kitosan-NP-ene ble syntetisert ved nanoutfellingsmetoden og de hydrodynamiske størrelsene ble målt med DLS og lumisizer. De fortynnede prøvestørrelsene var mellom 150-350 nm og konsentrerte prøvestørrelser var mellom 500-1200 nm. Størrelsesfordelingsanalysen observerte minste til største størrelse fra 371 nm til 3920 nm og gjennomsnittlig størrelse var 1271. Zetapotensialene til prøvene varierte mellom (-18 til -40 mV og 25-35 mV avhengig av ikke-løsningsmiddelfjerningsteknikk). Studiet av forskjellige parametere som polymerkonsentrasjon, molekylvekt, omrøringsvarighet og strømningshastighet som kan påvirke kitosan NP-størrelsen ble utført. FT-IR-data ble gjort for å observere de funksjonelle bindingstoppene til NP-ene og bekrefte overflateaktivt belegg på overflaten. STEM-karakterisering observerte polydisperse prøver og største partikkel var mellom 1-2 µm. Deretter ble IONP-er syntetisert ved co-presipiteringsmetode. De hydrodynamiske størrelsene og zetapotensialene var 176 ± 4 nm og -32 ± 0,3 mV. Størrelsesfordelingsanalysen observerte minste til største hydrodynamiske størrelse fra 24 nm til 39 nm og gjennomsnittlig størrelse var 39 nm. TEM-karakteristikkene observerte 10 ± 3 nm tørket partikkelstørrelse. FT-IR-data ble gjort for å observere de funksjonelle bindingstoppene til IONP-ene og VSM-data beviste superparamagnetisme-egenskapen. Kitosanbelagte IONP-er ble syntetisert ved nanoutfellingsmetode. En sammenligningsstudie ble gjort for å bekrefte at nanoutfellingsmetoden er bedre enn blandingsprosessen ved å observere deres hydrodynamiske størrelser og STEM-egenskaper. De hydrodynamiske størrelsene var mellom 900-1500 nm og zetapotensialet var mellom 25-30 mV. Zeta-potensialet kan tyde på at overflaten til NP-ene var belagt med kitosan. Størrelsesfordelingsanalysen observerte minste til største hydrodynamiske størrelse fra 58 nm til 261 nm og gjennomsnittlig størrelse var 91 nm. Overflatekarakterisering ble gjort ved å analysere det isoelektriske punktet og FT-IR-data. JMP-designet for studier av forskjellige parametere (polymerkonsentrasjon, IONPs-konsentrasjon, strømningshastighet og metanolvolum) ble utført ved bruk av screeningdesign. R2 var 0,22 som indikerte dårlig tilpasning for dette datasettet. Noe liten størrelsesoptimalisering ble gjort senere for å begrense de optimale parameterne for å syntetisere små NP-størrelser for biomedisinsk bruk. Nanomaterials are materials with at least one dimension in the billionth of a meter range (10-9 m). Significant research has been undertaken over the last two decades on the development and engineering of magnetic nanoparticles. Magnetic particles provide extremely efficient energy harvesting systems that have the potential to revolutionize current treatment and diagnostic procedures. The specific nature of the surface coating is crucial since it can impact important IONP features such as colloidal stability, toxicity, magnetism, and labeling efficiency. Polymers are commonly employed as IONP coatings because they can improve colloidal stability in hydrophilic circumstances and preserve the iron oxide core from degradation. In this study, chitosan was used for coating IONPs using nanoprecipitation method. This project was divided into three phases. Bare chitosan NPs synthesis, IONPs synthesis and lastly chitosan coated IONPs synthesis. The size, surface charge, molecular structure analysis and magnetic properties (IONPs only) were characterized of those particles. Preliminary study was also done by synthesizing PLGA NPs and PLGA-IONPs. The chitosan NPs were synthesized by nanoprecipitation method and the hydrodynamic sizes were measured by DLS and lumisizer. The diluted sample sizes were between 150-350 nm and concentrated sample sizes were between 500-1200 nm. The size distribution analysis observed smallest to largest size from 371 nm to 3920 nm and mean size was 1271. The zeta potentials of the samples ranged between (-18 to -40 mV and 25-35 mV depending on non-solvent removal technique). The study of different parameters like polymer concentration, molecular weight, stirring duration and flow rate that can influence the chitosan NP size was performed. FT-IR data was done to observe the functional bond peaks of the NPs and confirm the surfactant coating on the surface. STEM characterization observed polydisperse samples and largest particle was sized between 1-2 µm. Then IONPs were synthesized by co-precipitation method. The hydrodynamic sizes and zeta potentials were 176 ± 4 nm and -32 ± 0.3 mV. The size distribution analysis observed smallest to largest hydrodynamic size from 24 nm to 39 nm and mean size was 39 nm. The TEM characteristics observed 10 ± 3 nm dried particle size. FT-IR data was done to observe the functional bond peaks of the IONPs and VSM data proved the superparamagnetism property. Chitosan coated IONPs were synthesized by nanoprecipitation method. A comparison study was done to confirm nanoprecipitation method is better than mixing process by observing their hydrodynamic sizes and STEM characteristics. The hydrodynamic sizes were between 900-1500 nm and zeta potential were between 25-30 mV. The zeta potential could suggest the surface of the NPs were coated with chitosan. The size distribution analysis observed smallest to largest hydrodynamic size from 58 nm to 261 nm and mean size was 91 nm. Surface characterization was done by analyzing the isoelectric point and FT-IR data. The JMP design for study of different parameters (polymer concentration, IONPs concentration, flow rate and methanol volume) was performed using screening design. R2 was 0.22 which indicated a poor fit for this data set. Some small size optimization was done later to narrow down the optimum parameters to synthesize small NP sizes for biomedical application.

Liten gjennomsnittlig diameter sammen med smal partikkelstørrelsesfordeling er nødvendig for å gi en tilfredsstillende magnetisk metningsytelse av jernoksid nanopartikler for diagnostiske anvendelser. Bruken av polyvinylpyrrolidon (PVP) som et beleggmiddel har tidligere blitt rapportert av andre studier for å kontrollere partikkelstørrelsen, for å oppnå svært monodisperse partikler og for å redusere agglomerasjoner av jernoksid nanopartikler syntetisert ved samutfellingsmetoden. For så vidt er det imidlertid ingen rapporter som undersøker samspillet mellom faktorer som masse, molekylvekt, konsentrasjon, pH og zeta-potensial til PVP på overflaten av jernoksid nanopartikler med den hensikt å kontrollere størrelsen. Derfor rapporterer denne oppgaven optimalisering av kolloidal stabilitet ved bruk av ulike masser av jernoksid nanopartikler og ulike molekylvekter og konsentrasjoner av PVP for effektivt belegg, etterfulgt av silanisering. Størrelsen på PVP-belegget av jernoksid nanopartikler ser ut til å være betydelig avhengig av interaksjonen mellom de eksperimentelle faktorene med hydrodynamiske størrelser fra 177 til 1915 nm, mens zeta-potensialverdiene varierer fra 6 til 20 mV. Overflateladningen til zeta-potensialet ser ut til å være positiv og strukturell identifiseringsanalyse indikerer at det ikke er noen PVP-molekylkjeder tilstede i dispersjonen. Imidlertid avslører pH-studien at PVP er enten delvis eller svakt adsorbert, eller alternativt ingen PVP adsorbert på overflaten av jernoksid nanopartikler. Tilstedeværelsen av PVP ser heller ikke ut til å påvirke silaniseringsprosessen i betydelig grad. Resultatene viser at tilstedeværelsen av PVP ikke forbedrer den kolloidale stabiliteten og er potensielt ikke en utmerket kandidat for biomedisinske applikasjoner. Small average diameter along with narrow particle size distribution is required to provide a satisfactory magnetic saturation performance of iron oxide nanoparticles (IONPs) for diagnostic applications. The use of polyvinylpyrrolidone (PVP) as a coating agent has previously been reported by other studies to control the particle size, to obtain highly monodisperse particles, and to reduce agglomerations of IONPs synthesized by the co-precipitation method. To this extent, however, there are no reports examining the interplay between factors such as mass, molecular weight, concentration, pH, and zeta potential of PVP on the surface of IONPs with the intention of controlling the size. Thereby, this thesis reports the optimization of colloidal stability using various masses of IONPs and various molecular weights and concentrations of PVP for efficient coating, followed by silanization. The size of PVP coating of IONPs appears to be significantly dependent on the interaction between the experimental factors with hydrodynamic sizes ranging from 177 to 1915 nm, whereas the zeta potential values vary from 6 to 20 mV. The surface charge of the zeta potential appears to be positive and structural identification analysis indicates that there are no PVP molecule chains present in the dispersion. However, the pH study reveals that PVP is either partially or weakly adsorbed, or alternatively no PVP adsorbed on the surface of IONPs. The presence of PVP also does not appear to affect the silanization process significantly. The results show that the presence of PVP does not improve the colloidal stability and is potentially not an excellent candidate for biomedical applications.

De siste tiårene har det vært en kraftig økning i omfanget av forskning på nanopartikler av jernoksid, på grunn av dets anvendelse i flere potensielle applikasjoner innenfor ulike fagfelt, som blant annet biomedisin, vannbehandling og katalyse. En av de mange overlegne egenskapene er høy magnetisme, hvilket kombinert med funksjonalisering av nanopartiklene med polymere som kan binde biomolekyler, åpner opp for muligheten av rask og målrettet ekstrahering av biomolekyler ved magnetisk separasjon. Et eksempel på en slik polymer er poly(akrylsyre) (PAA) som ved belegning sørger for frie karboksylgrupper på overflaten av nanopartiklene. Flere grupper har tidligere rapportert PAA-belegning av jernoksid nanopartikler som er syntetisert ved samutfelling, men det finnes få studier hvor jernoksid nanopartikler syntetisert ved termisk nedbryting er benyttet til dette formålet. I denne avhandlingen ble det studert flere metoder for å syntetisere jernoksid nanopartikler ved termisk nedbrytning. Et utvalg av disse ble enten overført fra organisk til vandig fase eller belagt med PAA for å skaffe frie karboksylgrupper på overflaten av nanopartiklene. Karakterisering av de funksjonaliserte jernoksid nanopartiklene viste at PAA-belegning gav størst mengde av karboksylgrupper på overflaten sammenlignet med karboksylfunksjonalisering ved faseoverføring. Likevel viste demonstrasjonen av anvendelse av jernoksid nanopartiklene til ekstraksjon av nukleinsyre, at prestasjonen var uavhengig av antall karboksylgrupper. Sammenlignet med PAA-belagte jernoksid nanopartikler syntetisert ved samutfelling, utviste to av de foreslåtte karboksylfunksjonaliserte jernoksid nanopartiklene prestasjon på samme nivå. Alle de funksjonaliserte jernoksid nanopartiklene utviste superparamagnetiske egenskaper ved romtemperatur, hvor den mest lovende metoden ga magnetisk metning på 76 emu/g. For videre arbeid foreslås det å se videre på hvordan størrelse og mengde av karboksylgrupper på kubiske jernoksid nanopartikler kan optimaliseres for å tilpasses spesifikke applikasjoner innenfor diagnostikk. Investigation and research of iron oxide nanoparticles (IONPs) have experienced rapid growth over the last decades due to their vast potential applications within multiple fields, such as biomedicine, water treatment and catalysis. One of the many superior properties is the great magnetism exhibited, which, combined with functionalizing the nanoparticles with polymers that can bind biomolecules, enables the possibility of rapidly extracting targeted biomolecules using magnetic separation. An example of such a polymer is poly(acrylic acid) (PAA) which by coating provides free carboxyl groups on the surface of the nanoparticles. Multiple groups have previously reported PAA-coating of IONPs synthesized by coprecipitation, but there are few studies on using IONPs synthesized by thermal decomposition for this purpose. In this thesis, several methods for synthesizing IONPs by thermal decomposition were looked into. A selection of the obtained nanoparticles was either transferred from organic to aqueous phase or coated with PAA to provide free carboxylic groups on the surface of the nanoparticles. Characterizing the functionalized IONPs showed that PAA-coating gave the highest amount of carboxylic group on the surface compared to carboxyl-functionalization by phase transfer. Still, the demonstration of using the IONPs in nucleic acid extraction showed good performance regardless of the number of carboxyl groups. Compared to PAA-coated IONPs synthesized by coprecipitation, two of the proposed carboxyl-functionalized IONPs showed the same level of performance. All the functionalized IONPs exhibited superparamagnetic properties at room temperature, and the most promising method gave saturation magnetization at 76 emu/g. For further studies, it is proposed to look into how the size and carboxylic content on cubic-shaped IONPs can be optimized to fit specific applications in diagnostics.

Covid-19 pandemien har demonstrert nødvendigheten av billige, robuste og sensitive biosensorer. Gull-nanopartikler av anisotrope former har unike optiske egenskaper, og har derfor potensiale til å radikalt forbedre dagens biosensor teknologi. For å fremstille slike partikler står «Seed mediated growth» frem som en anerkjent og effektiv metode. Dessverre har de fremstilte partiklene CTAB på overflaten, noe som gir utfordringer med stabilitet i anvendelser. Nanopartiklene må derfor funksjonaliseres videre. Bedre forståelse av hvordan overflate-funksjonalisering endrer egenskapene til gull nanopartikler, og utvikling av robuste og effektive metoder for overflate-funksjonalisering er derfor viktig for fremskritt i biosensor teknologi. Hovedmålet i denne masteroppgaven er å bidra til forståelsen av overflate funksjonalisering av CTAB-belagte Gull-Nanopartikler, og spesielt undersøke om funksjonaliseringen avhenger av formen til partiklene. Først ble fire gull-nanopartikler prøver fremstilt og karakterisert ved å bruke «CTAB-mediated seeded growth synthesis route». I tillegg ble en citrate-belagt fire gull-nanopartikler prøve fremstil ved Turkeivch metode. Deretter ble karakterisering av konsentrasjon med metodene MP-AES, Zetaview og UV-vis studert. Ulike måleenheter for konsentrasjons kan være en forbedret måte å tilpasse overflate funksjonaliserings protokoller til nye nanopartikkel prøver. MP-AES viste et maksimalt standard avvik på 0.01 mg/ml, og oppløsningen var begrenset av polydisersitet og inhomogene dispersjoner i prøvene. UV-Vis kunne brukes til å måle konsentrasjon når nanopartiklene hadde lik størrelse og overflatekjemi. Hydrodynamisk diameter er et praktisk verktøy for å overvåke hvordan overflatekjemien endrer seg. En robust protokoll for reproduserbare målinger av anisotrope gull nanopartikler var derfor av interesse. To stavformede nanopartikkel prøver ble derfor målt ved ulike fortynninger og deteksjonsvinkler, og studien konkluderte med surfaktant stabiliserte nanopartikler bør måles med lavest mulig fortynningsfaktor for mest mulig reproduserbare målinger. En to trinns protokoll for PEG and MUA overfalte funksjonalisering ble optimalisert ved å bruke stavformede gull nanopartikler. Målet var å erstatte CTABen på overflaten med PEG. Den høyeste effektiviteten ble funnet ved bruk av 2.56 mg/ml PEG og 20 mM MUA. Denne protokollen ble anvendt på de fem gull nanopartiklene. Det ble ikke påvist noen avhengighet til form. Oppgaven diskuterer om det er mulig å ta bedre vare på de optiske «LSPR»-egenskapene til prøvene, eller om uhomogen overflate funksjonalisering, økt størrelse og polydispersitet gjør dette umulig. Videre studier av stabilitet, reaktiviteten til karboksylgruppene og sonikerings metoder ble foreslått. Til slutt ble biotin bundet til de funksjonaliserte gull nanopartiklene, og testet i et modell biosensor system med streptavidin. Runde gullnanopartikler viste ingen tegn til aggregering ved økende mengder streptavidin. Til forskjell viste stavformede nanopartikler et maksimalt rødskift på 13 nm i den longitudinale «LSPR-peak»-en ved 75 nM streptavidin. Dette indikerer at modell biosensor systemet kan bli et verdifullt verktøy for testing av refraktiv indeks sensitivitet for karboksyl funksjonaliserte gull nanopartikler. Resultatene i studien tilsa at forbedring av partiklenes stabilitet i buffer bør være hovedfokuset i videre utvikling. Dette bør inneholde forskning på bindingsstyrken av PEG og MUA til gull-nanopartiklene.

Biosensorer er i dag uerstattelige verktøy i svært mange biomedisinske felt, inkludert klinisk diagnostikk. Flere virus, som blandt annet humant immunsvikt virus (Hiv), hepatitt B-virus (HBV) og morbillivirus (meslingevirus), kan identifiseres ved bruk av biosensor-teknologi. Utbruddet av koronaviruset (COVID-19) er et utmerket eksempel på hvordan tidlig påvisning av en virusinfeksjon er avgjørende for å forhindre spredning av sykdommen. Dagens biosensorer begrenses av både sensitiviten og selektiviteten på biomolekylet som skal detekteres, i tillegg til at selve deteksjonen ofte er en tidskrevende prosess. Å lage biosensorer ved bruk nanoteknologi, kan bidra til å øke kvaliteten på biosensorer betraktelig. Magneto-plasmoniske nanopartikler (NP) er partikler bestående av et magnetisk og et plasmonisk materiale fusjonert sammen til én nanopartikkel. Grunnet deres to-delte natur, har disse partiklene både en lokal overflate plasmon resonansfrekvens (LSPR) og superparamagnetisk oppførsel. I løpet av dette arbeidet har anisotrope magneto-plasmoniske partikler blitt syntetisert gjennom heterogen vekst av gull på forskjellige typer jern-holdige NP kjerner. Ved å variere egenskapene til kjernene og reaksjonsbetingelsene for syntesen, ble egenskapene til de resulterende partiklene justert til å være optimale til bruk i biosensor-teknologi. Det ble funnet at det å bruke cetyltrimetylammoniumbromid dekte jern-oksid (IO-CTAB) NP kjerner, i en vekstløsning med lavt sølvnitratinnhold kombinert med en høy pH, resulterte i de anisotrope magneto-plasmoniske NP som var mest egnet til bruk i biosensing. Today, biosensors are ubiquitous in a wide range of biomedical applications, including clinical diagnostics. Several viruses, including the human immunodeficiency virus (HIV), hepatitis B virus and the measles virus, have already been successfully detected using biosensing technology. The outbreak of coronavirus disease (COVID-19), is an excellent example on how early detection of infection is crucial in preventing the spread of a virus. However, the applications of many of today's biosensors are restricted due to the sensor's level of sensitivity and selectivity to the target molecule, as well as being time-consuming processes. Nanomaterial-based biosensors can be a good alternative in order to overcome these challenges. Magneto-plasmonic nanoparticles (NPs) are particles composed of one magnetic and one plasmonic material combined together into a single nanoparticle through solid-solid interfaces. Due to their dual nature, these particles exhibit both a local surface plasmon resonance (LSPR) and superparamagnetic behavior. In this work, anisotropic magneto-plasmonic particles have been synthesized by seed-mediated growth of gold on different iron-containing NPs. By varying the properties of the seed and the reaction conditions of the synthesis, the physico-chemical properties of the resulting particles were tuned to be optimal for use in biosensing applications. It was found that the cetyltrimethylammonium bromide capped iron oxide (IO-CTAB) NP seeds, used in a growth solution with a low silver nitrate content combined with a high pH, resulted in the anisotropic magneto-plasmonic NPs most suitable for biosensing applications.

Iron Oxide Nanoparticles (IONPs) have been extensively used in different applications including biomedicine, hydrology, and catalysis. This is because IONPs have excellent physico-chemical properties like superparamagnetism. These IONPs can be encapsulated into various polymers using different techniques like emulsion-diffusion, salting out, and nanoprecipitation whereby increasing their applicability in various fields. Many researchers have investigated the encapsulation of hydrophobic moieties into polymers by the using the technique of nanoprecipitation but very few research papers have been published where hydrophilic moieties are encapsulated into polymers by the above-mentioned technique. The aim of this project was to encapsulate the hydrophilic moieties i.e., IONPs into different polymers by using nanoprecipitation. In this master thesis, firstly IONPs and bare polymeric NPs of PLGA were synthesized using the technique of co-precipitation and nanoprecipitation, respectively in section 4.1. Secondly, IONPs were then encapsulated by PLGA NPs using the technique of nanoprecipitation. This encapsulation process was optimized via different methodology which are briefly discussed in section 4.2. Thirdly, the study of different parameters like polymer amount, amount of IONPs, Aqueous/Organic ratio and injection rate that can influence the PLGA encapsulated IONPs size was performed using a statistical software i.e., JMP in section 4.3. Finally, in the last section 4.4, bare PLGA NPs and PLGA encapsulated IONPs were loading with a hydrophobic drug i.e., coumarin. The IONPs were characterized using High Resolution Transmission Electron Microscopy (HRTEM), PLGA encapsulated IONPs were characterized using Dynamic Light Scattering (DLS) and drug loading efficiency was estimated using Ultra Violet Visible Spectroscopy (UV-Vis). The IONPs synthesized by co-precipitation method had polydisperse population with an average diameter of 15 ± 2 nm. The hydrodynamic size of PLGA NPs before encapsulation with the IONPs was in the range of 80-110 nm. After encapsulation of the IONPs with PLGA NPs, the hydrodynamic size was obtained in the range from 400-800 nm. The process of encapsulation of IONPs with PLGA NPs was successfully optimized using different methodologies. The JMP design for study of different parameters was performed using screening design. In screening design, backward selection of the least significant variable in the data set is done. Because the least significant variable has the maximum effect on the data set. In the first JMP design, Fe/Polymer ratio and molecular weight of polymer were the least significant variables. In the second JMP study, molecular weight, and amount of IONPs were found to be the least significant variables. In the last study, coumarin was loaded in PLGA NPs and PLGA encapsulated IONPs. The drug loading efficiency for bare PLGA NPs was found to be around 92 % and for PLGA encapsulated IONPs it was around 90 % when highest amount of drug was used. Hence, in this project, successful encapsulation of IONPs (hydrophilic moieties) and drug loading of coumarin in PLGA encapsulated IONPs was achieved by the technique of nanoprecipitation which has not been reported in the literature until date.

Jern oxyhydroxide har blitt utfelt i en løsning sammen med fluorid i en Mixed-Suspension-Mixed-Product-Removal(MSMPR) Reaktor ved forskjellige temperaturer, oppholdstider og sulfat konsentrasjoner. Temperaturnivåene benyttet var 25°C og 60°C, oppholdstid nivåene var 30 min og 45 min, mens sulfat konsentrasjonene var 0, 10 and 20 g/L. Virkningen disse parameterne hadde på utfellingen og fluorid adsorptionen ble studert. Hvor krystallinsk utfellingen var, ble redusert med synkende temperaturer og økende sulfat konsentrasjoner. Utfellingen uten sulfat var 70-80 % akaganeite, mens utfellingen når sulfat konsentrasjonen var 20 g/L bestod kun av noen prosent akaganeite, mens det hadde en høy andel schwermannite. Konsentrasjonen til fluorid i strømmen in til reaktoren var 100 mg/L. andelen som var igjen i filtratet varierte mellom 1.59 mg/L med en temperatur på 60°C, oppholdstid på 30 min Og ikke noe sulfat, til 33.43 mg/L med en temperatur på 25°C, oppholdstid på 45 min og 20 g/L sulfat. Hoved effekten til temperaturen og sulfat konsentrasjonen hadde en betydelig effekt, det samme hadde interaksjonene mellom dem Iron oxyhydroxides have been precipitated in the presence of fluoride using a Mixed-Suspension-Mixed-Product-Removal(MSMPR) Reactor at different temperatures, residence times and concentrations of sulphate. The levels of temperature used were 25°C and 60°C, the levels of residence time were 30 min and 45 min, while the sulphate concentrations were 0, 10 and 20 g/L. The effect these parameters had on the precipitate and fluoride adsorption were studied. The crystallinity of the precipitate decreased with decreasing temperature and increasing sulphate concentration. The precipitates without sulphate were 70-80 % akaganeite, while at a sulphate concentration of 20 g/L, the precipitate were only a few per cent akaganeite, while it had a high percentage of schwertmannite. The concentration of fluoride in the flows entering the reactor where 100 mg/L. The amount left in the filtrate varied between 1.59 mg/L at a temperature of 60°C, residence time of 30 min and no sulphate, to 33.43 mg/L at a temperature of 25°C, residence time of 45 min and 20 g/L of sulphate. It was determined that the main effect of temperature and sulphate concentration were significant, and that they had a significant interaction.

Carbon nanotubes has been a hot topic in the last 30 years as "the future material of manufacturing and electronic compounds". Besides this, the world is under high distress trying to abate the climatic effects of greenhouse gases such as carbon dioxide. Bergen carbon solutions AS is a startup company developing CNFs from carbon dioxide by molten electrocatalysis to add value to the economy using CO2 as a resource. However, the applicability of this magnificent material is restricted to the carbonaceous and transition metal impurities in the end product. Such impurities has proved to be a challenge to eliminate ever since tubular nanomaterials were discovered. In spite of this, several methods from scientific literature have been compared and evaluated to propose the most suitable cleansing technique for the company for an efficient and low cost upscaling of their carbon manufacturing. The result of Goaks method are superior to others. However, adapting a multistep method which also applies magnetic separation and Fenton chemistry is also a promising low cost alternative to achieve the highly applicable, ECO-C1 grade purity at a large scale.

Studiet av anisotrope gullnanopartikler (AuNPs) og deres vekst er et område av stor interesse på grunn av deres bemerkelsesverdige biokompatible og plasmoniske egenskaper. Disse egenskapene er sterkt avhengig av størrelse og form, noe som gjør det nødvendig å forstå veksten og justere metoden for å få kontroll over formene og egenskapene til AuNPs. Dette arbeidet fokuserer på «seed-mediated», sølvassistert vekst av AuNPs og utvidelse av kunnskapen innhentet av Raghunathan et al. og i prosjektoppgaven min. En eksperimentell tilnærming for å forstå veksten ble brukt, og effekten av reduserende middel, oljesyre (OA), pH og ioner var i hovedfokus. Effekten av varierende mengder OA ble utforsket med et alternativt reduksjonsmiddel, Tannic Acid (TA), i en «screeningsdesign» bestående av 13 eksperimenter. pH og mengde sølvnitrat ble også variert. Matematiske modeller ble laget basert på de resulterende lengdene og sideforholdene til partiklene, og det ble funnet at syntesene sjelden ga AuNPs ved pH 1,5. En høyere pH-verdi (11) og en høyere mengde OA (200 uL) ble studert. For å utforske virkningene av pH nærmere, ble effekten av ionene som ble tilsatt for å endre pH undersøkt ved å tilsette den samme mengden ioner på forskjellige tidspunkt i syntesen. Dette ble gjort med 0, 20 og 200 uL OA. Det ble sett at mengden OA hadde en dominerende effekt på systemet, mens tiden for tilsetning av ioner hadde liten eller ingen effekt på sluttproduktet. Karakterisering av AuNPs ble hovedsakelig gjort ved bruk av UV-Vis og S(T)EM. Utbytte ble studert ved hjelp av MP-AES for noen av syntesevariantene. Utbyttet ble funnet å være 12.2, 25.3 og 94.9 % for henholdsvis syntese uten sølv, med sølv og med sølv og 20 uL OA. Dette pekte mot den doble rollen til OA som «co-surfactant» og reduserende middel. Til slutt ble arbeidet avrundet med en diskusjon rundt mulige vekstmekanismer. The study of anisotropic gold nanoparticles (AuNPs) and their growth is an area of great interest due to their remarkable biocompatible and plasmonic properties. These properties are highly size- and shape-dependent, making it necessary to understand the growth and to tune the method to gain control over the shapes and properties of the AuNPs. This work focuses on the seed-mediated, silver-assisted growth and expanding the knowledge obtained by Raghunathan et al. and the knowledge gained in my project leading up to this work. An experimental approach to understand the growth was used, exploring the effects of the reducing agent, Oleic Acid (OA), pH and ions as the main topics. The effects of varying amounts of OA were explored with an alternative reducing agent, Tannic Acid (TA), in a screening design consisting of 13 experiments. The pH and amount of AgNO_3 were also varied. Mathematical models were made based on the fit from the resulting lengths and aspect ratios, and it was found that the syntheses rarely yielded AuNPs at pH 1.5. A higher pH (11) and a higher amount of OA (200 uL) were studied. Further, to decouple the effects of pH, the effect of the ions added to change the pH were investigated by adding the same amount of ions at different times in the synthesis. This was done with 0, 20 and 200 uL OA. It was seen that the amount of OA had a dominating effect on the system, while the time of adding ions had little to no effect on the final product. Characterization of the final AuNPs was mainly done by UV-Vis and S(T)EM. A yield study was conducted using microwave plasma atomic emission spectrometry for some of the syntheses variations. The yield was found to be 12.2, 25.3 and 94.9 % for syntheses without silver, with silver and with silver and 20 uL OA, respectively. This pointed towards the dual role of OA as co-surfactant and reducing agent. Finally, the work was rounded off by a discussion around possible growth mechanisms.

Nanomaterials have gained a lot of attention in the past few decades as potential candidates for biomedical applications. Currently, research with different nanomaterials is being carried out for enhancing existing in-vivo imaging techniques, wound dressing, tissue engineering, heat induced treatment and targeted drug delivery, where polymeric and inorganic nanoparticles have shown wide potential. These materials have not only been engineered individually for specific applications, but also combined for producing hybrid systems in order to address multiple areas at once.(1) Two materials that have specifically caught attention are hydrogels and iron oxide nanoparticles (IONPs). The high-water affinity of hydrogels makes them flexible and soft emulating properties of living tissues. They also exhibit good biocompatibility and biodegradability, thus proving to be interesting materials for usage in field of biomedicine.(2) These materials can also be engineered to incorporate multiple stimuli-responsive properties that are sensitive to light, heat, pH, radiation, and electrical signals. Thus, multi-responsive hydrogels have previously been utilized and have shown potential as targeted drug delivery devices, with low toxicity and undesired side effects as compared to conventional techniques. Parallelly, IONPs have also gained wide importance in therapeutics and theranostics over the past two decades due to the possibility of controllable synthesis, thereby producing extremely small (< 20 nm) particles, having different morphology, high monodispersity, and unique superparamagnetic properties.(3, 4) By utilizing their superparamagnetic characteristic, heat can be generated from IONPs on exposure to alternating magnetic fields (AMF), at radio frequency region.(5) This has opened up a field of treatment, called hyperthermia, whereby the heat produced from IONPs can be used for cell apoptosis (killing).(6) However, unwanted, and uncontrolled production of heat can also affect healthy cells and tissues leading to side effects. Utilizing hydrogels to surface engineer IONPs, for producing hybrid structures could be the next potential solution for mitigating the above stated problem. Henceforth, heat produced from IONPs could be localized or controlled with hydrogel coating and could be utilized to trigger release of bioactive agents from these hybrid structures, thus, making treatments more target specific with less side effects. The stimuli-responsive contribution from hydrogels could also be engineered, making these hybrid systems even more efficient. In this work, controlled and reproducible synthesis of monodisperse IONPs (16 ± 2 nm) (in organic media) was done using thermal decomposition method. The synthesized IONPs were phase transferred from organic to aqueous media using sodium citrate, in order to make the IONPs dispersible in water, which forms the steppingstone for biomedical application. Sodium citrate electrostatically stabilized the IONPs in water, which was seen from negative zeta potential values, measured using Dynamic Light Scattering (DLS). The stability of these particles was also tested at elevated temperatures (45 ºC and 60 ºC), prolonged storage periods (2 months) and different pH conditions ranging from acidic to alkaline (pH 3 to 8) before being used further. Heat generation of these particles were also studied at optimized AMF condition (587 kHz, 12 mT). These particles showed significantly low specific absorption rates (SAR) (1.76 W/g) as compared to conventional magnetite NPs, which was also in accordance with the concept of achieving controlled heating. Parallelly, a hydrogel, (poly- (N-isopropyl acrylamide-acrylic acid)) was tailored with thermal and pH responsive properties. These systems showed collapse efficiencies ~ 97 % at 45 ºC and also reduction in hydrodynamic size (~ 63 nm) was seen at acidic pH=3.5 condition. Two systems; phase transferred IONPs and NGs, were characterized individually and used in conjunction to synthesize hybrid NGs with potential of being utilized as drug delivery devices. Hybrid NGs were synthesized using three different techniques, with the idea of producing hybrid systems with different physico-chemical properties which could open up new opportunities as novel drug-delivery systems. With difference in synthesis techniques, the hybrid systems showed different thermo-responsive properties which was analyzed by studying the collapses of these systems at elevated temperatures (45 ºC). The systems were superparamagnetic and also pH responsive, which showed retention of magnetic properties from IONPs and pH responsive properties from NGs polymeric structures when combined together. Henceforth, successful synthesis of hybrid systems with thermal, pH and magneto-responsive properties were shown in this study. The hybrid systems were then loaded with a model protein, Cytochrome C (cyt C), and the effect of thermal and pH responsive properties of hybrid systems on release of cyt C was studied under condition – 40 ºC and pH (3.5). The release of cyt C was tracked using UV-Vis spectroscopy (UV-vis) for ~ 20 hours and the release profiles obtained were fitted with common mathematical models and analyzed. Hybrid NGs synthesized via in situ technique showed slowest release rates for the first two hours (0.08 hour-1) as compared to other hybrid systems, showing potential as slower or sustained release systems. Lastly, to understand how magneto-responsive properties of these hybrid systems effected release of cyt C, release studies were done under AMF condition for 10 hours. A major challenge faced during this study, was unwanted production of background heat from water due to formation of eddy currents. Henceforth, optimizations were tried, to mitigate the background heat signal. Real-time monitoring of the temperature within the systems were performed for the entire duration of the study. No noticeable changes in release profile of cyt C was seen on exposure to AMF condition. This was because the release signal of cyt C due to controlled heat produced from hybrid systems were masked by background heating effects.