Tesi sul tema "Self-Assembly of block copolymers"

Block copolymers are receiving increasing attention in the literature. Reports on amphiphilic block copolymers have now established the basis of their self-assembly behavior: aggregate sizes, morphologies and stability can be explained from the absolute and relative block lengths, the nature of the blocks, the architecture and also solvent selectiveness. In water, self-assembly of amphiphilic block copolymers is assumed to be driven by the hydrophobic. The motivation of this thesis is to study the influence on the self-assembly in water of A b B type block copolymers (with A hydrophilic) of the variation of the hydrophilicity of B from non-soluble (hydrophobic) to totally soluble (hydrophilic). Glucose-modified polybutadiene-block-poly(N-isopropylacrylamide) copolymers were prepared and their self-assembly behavior in water studied. The copolymers formed vesicles with an asymmetric membrane with a glycosylated exterior and poly(N-isopropylacrylamide) on the inside. Above the low critical solution temperature (LCST) of poly(N-isopropylacrylamide), the structure collapsed into micelles with a hydrophobic PNIPAM core and glycosylated exterior. This collapse was found to be reversible. As a result, the structures showed a temperature-dependent interaction with L-lectin proteins and were shown to be able to encapsulate organic molecules. Several families of double hydrophilic block copolymers (DHBC) were prepared. The blocks of these copolymers were biopolymers or polymer chimeras used in aqueous two-phase partition systems. Copolymers based on dextran and poly(ethylene glycol) blocks were able to form aggregates in water. Dex6500-b-PEG5500 copolymer spontaneously formed vesicles with PEG as the “less hydrophilic” barrier and dextran as the solubilizing block. The aggregates were found to be insensitive to the polymer's architecture and concentration (in the dilute range) and only mildly sensitive to temperature. Variation of the block length, yielded different morphologies. A longer PEG chain seemed to promote more curved aggregates following the inverse trend usually observed in amphiphilic block copolymers. A shorter dextran promoted vesicular structures as usually observed for the amphiphilic counterparts. The linking function was shown to have an influence of the morphology but not on the self-assembly capability in itself. The vesicles formed by dex6500-b-PEG5500 showed slow kinetics of clustering in the presence of Con A lectin. In addition both dex6500-b-PEG5500 and its crosslinked derivative were able to encapsulate fluorescent dyes. Two additional dextran-based copolymers were synthesized, dextran-b-poly(vinyl alcohol) and dextran-b-poly(vinyl pyrrolidone). The study of their self-assembly allowed to conclude that aqueous two-phase systems (ATPS) is a valid source of inspiration to conceive DHBCs capable of self-assembling. In the second part the principle was extended to polypeptide systems with the synthesis of a poly(N-hydroxyethylglutamine)-block-poly(ethylene glycol) copolymer. The copolymer that had been previously reported to have emulsifying properties was able to form vesicles by direct dissolution of the solid in water. Last, a series of thermoresponsive copolymers were prepared, dextran-b-PNIPAMm. These polymers formed aggregates below the LCST. Their structure could not be unambiguously elucidated but seemed to correspond to vesicles. Above the LCST, the collapse of the PNIPAM chains induced the formation of stable objects of several hundreds of nanometers in radius that evolved with increasing temperature. The cooling of these solution below LCST restored the initial aggregates. This self-assembly of DHBC outside any stimuli of pH, ionic strength, or temperature has only rarely been described in the literature. This work constituted the first formal attempt to frame the phenomenon. Two reasons were accounted for the self-assembly of such systems: incompatibility of the polymer pairs forming the two blocks (enthalpic) and a considerable solubility difference (enthalpic and entropic). The entropic contribution to the positive Gibbs free energy of mixing is believed to arise from the same loss of conformational entropy that is responsible for “the hydrophobic effect” but driven by a competition for water of the two blocks. In that sense this phenomenon should be described as the “hydrophilic effect”.<br>Blockcopolymere erfahren ein stetig wachsendes Interesse, was an der steigenden Anzahl an Publikationen zu diesem Thema erkennbar ist. Zahlreiche Studien zu amphiphilen Blockcopolymeren haben dabei einige grundlegende Erkenntnisse über deren chemisches und physikalisches Verhalten, vor allem über die Selbstorganisation, hervorgebracht. So können die Größe, die verschiedenen Morphologien und auch die Stabilität der gebildeten Aggregate anhand der relativen und absoluten Blocklängen, die chemischen Struktur der Blöcke, der molekularen Architektur und der Eigenschaften des verwendeten Lösungsmittel erklärt werden. Im speziellen Fall des Wassers als Lösungsmittel bist die Selbstorganisation amphiphiler Blockcopolymere durch den hydrophoben Effekt bedingt. Dieser Arbeit liegt das Interesse an der Selbstorganisation in wässrigem Medium von Blockcopolymeren des Typs A-b-B mit A als hydrophilem Block und B als Block mit variierender Hydrophilie bzw. Hydrophpobie von unlöslich bis vollständig löslich zugrunde. Durch Variation dieser Eigenschaften von Block B soll dessen Einfluss auf das Selbstorganisationsverhalten untersucht werden. Dazu wurden mit Glucose modifizierte Polybutadien-block-Poly(N-Isopropylacrylamid)-Copolymere hergestellt und deren Selbstorganisation in Wasser untersucht. Die Copolymere bilden Vesikel mit einer asymmetrischen Membran, wobei im äußeren Bereich glycolysierte Gruppen und im inneren Bereich Poly(N-Isopropylacrylamid) (PNIPAM) vorliegen. Beim Überschreiten der low critical solution temperature (LCST) kollabiert die vesikuläre Struktur unter Bildung von Mizellen mit einem hydrophoben PNIPAM-Mizellinneren und nach außen gerichteten glycolysierten Blöcken. Diese strukturelle Umwandlung ist reversibel. Die Strukturen zeigten außerdem eine temperaturabhängige Wechselwirkung mit L-Lectin-Proteinen und die Möglichkeit zur Einkapselung organischer Moleküle konnte belegt werden. Des weiteren wurden verschiedene Gruppen von Blockcopolymeren mit zwei hydrophilen Blöcken synthetisiert (double hydrophilic block copolymers – DHBC). Die Blöcke dieser Systeme waren entweder Biopolymere oder Polymerchimäre, die in wässrigen Zwei-Phasen-Trennverfahren eingesetzt werden. Polymere, die auf Dextran- und Poly(ethylenglycol)-Blöcken basieren, zeigen Aggregatbildung in wässriger Phase. Dex6500-b-PEG5500 bildet spontan Vesikel mit PEG als „weniger hydrophilem“ Bestandteil und Dextran als löslichem Block. Die Bildung dieser Vesikel zeigte keine Emfpindlichkeit gegenüber einer Veränderung der Polymerarchitektur und der Konzentration, und nur eine geringe Sensitivität gegenüber Temperaturänderungen. Veränderungen der Blocklängen dagegen beeinflussten die Selbstorganisation und führten zu unterschiedlichen Morphologien. Längere PEG-Blöcke bevorzugten dabei die Bildung eher gekrümmter Aggregate, entgegen dem Trend, der gewöhnlicherweise für amphiphile Blockcopolymere beobachtet wird. Die Verkürzung des Dextran-Blocks fördert die Ausbildung vesikulärer Strukturen, was dem Verhalten der amphiphilen Gegenspieler der DHBC-Systeme entspricht. Die funktionelle Gruppe zur Verbindung der beiden Blöcke hat zwar einen Einfluss auf die Morphologie der gebildeten Aggregate, nicht jedoch auf die eigentliche Fähigkeit der Systeme zur Selbstorganisation. Die Dex6500-b-PEG5500-Vesikel wiesen zudem eine langsame Bildungskinetik in Gegenwart von Con-A-Lectin auf. Des Weiteren waren sowohl Dex6500-b-PEG5500 als auch das quervernetzte Derivate dieses Copolymers in der Lage, Fluoreszenzfarbstoffe einzulagern. Um zu zeigen, dass wässrige Zwei-Phasen-Systeme (aqueous two phase systems – ATPS) eine belastbare Grundlage für die Untersuchung und Entwicklung selbstorganisierender DHBC-Systeme sind, wurden weitere Dextran-basierte Copolymere synthetsisiert: Dextran-b-Poly(vinylalokohol) und Detran-b-Poly(vinylpyrrolidon). In einem zweiten Teil dieser Arbeit wurde das zuvor erarbeitete Prinzip auf auf Polypeptidsysteme ausgeweitet. Dazu wurde ein Poly(N-Hydroxyethylglutamin)-block-Poly(ethylenglycol)-Copolymer hergestellt. Dieses Copolymer, dessen emulgierenden Eigenschaften bereits bekannt waren, wies unmittelbar nach Lösung des Feststoffes in Wasser Vesikelbildung auf. In einem dritten Teil der Studie wurden thermoresponsive Copolymere hergestellt und untersucht: Dextran-b-PNIPAMm. Unterhalb der LCST konnte die Bildung von Aggregaten nachgewiesen werden, deren Struktur nicht zweifelsfrei entschlüsselt werden konnte, wobei jedoch zahlreiche Hinweise auf eine vesikuläre Struktur hindeuten. Oberhalb der LCST wurde durch die Kollabierung der PNIPAM-Ketten die Bildung stabiler Strukturen mit Radien von mehreren hundert Nanometern induziert, deren weitere Entwicklung durch eine weitere Temperaturerhöhung gefördert werden konnte. Durch Rückkühlung in den Temperaturebereich unterhalb der LCST konnten die zuvor beobachteten Aggregate reversibel zurückgebildet werden. Das Selbstorganisationsverhalten von DHBC, unabhängig vom Einfluss des pH-Werts, der Ionenstärke oder der Temperatur are bisher nur in sehr geringem Umfang Gegenstand wissenschaftlicher Veröffentlichungen. Diese Arbeit stellt damit den ersten umfassenden Beitrag zur systematischen Erarbeitung dieses Phänomens dar. Es konnten dabei zwei Ursachen für die beobachteten Selbstorganisationseffekte bestimmt werden: die Inkompatibilität der beiden Polymerblöcke (enthalpischer Effekt) und der Unterschied in deren Löslichkeit (enthalpische und entropische Effekte). Der entropische Beitrag zur positiven Gibbs’schen Freien Mischungsenergie wird dem selben Verlust konformativer Entropie zugeordnet, der auch für den hydrophoben Effekt verantwortlich ist, allerdings angetrieben durch einen Wettbewerb der beiden Polymerblöcke um das Wasser. In diesem Sinne kann man das beobachtete Phänomen als „hydrophilen Effekt“ bezeichnen.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 2019<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references.<br>Self-assembly of block copolymers (BCPs) is emerging as a promising route for numerous technological applications to fabricate a variety of nanoscopic structures. The resulting feature sizes range from a few to several hundred nanometers, and are readily tunable by varying the molecular weights of block copolymers. Directed self-assembly of block copolymer is an effective way to pattern periodic arrays of features with long-range order, to generate complex patterns, and to multiplicatively increase the pattern density and resolution that are far beyond the limit of conventional lithography. Despite of the significant progress in the area of directed self-assembly in recent years, critical research problems regarding the dimension scalability toward sub-10-nm regime and large feature sizes on hundreds of nanometers scale as well as the capability of generating complex device-oriented patterns remain challenging. In this thesis, BCP systems, including high-v BCPs that are capable of self-assembling into extreme small and large feature sizes as well as those with more complex block architectures, are identified and studied in order to understand how those materials may be processed and directed selfassembly to bridge the patterning size spectrum between nano- and micro-fabrication. Another focus is placed on the scientific exploration of directed self-assembly of triblock terpolymers and the investigation on the mechanisms that regulate the scaling and geometry of self-assembled patterns. A comprehensive understanding about self-assembly of BCP thin films will enable developing device-oriented geometries, manipulating BCPs phase behavior, and incorporating new functional materials for a wider range of applications. In the meanwhile, optimizing the processing condition of self-assembly of various BCPs is essential to confirm viability of the directed self-assembly of block copolymers process in manufacturing.<br>by Li-Chen Cheng.<br>Ph. D.<br>Ph.D. Massachusetts Institute of Technology, Department of Materials Science and Engineering

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2009.<br>This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.<br>Cataloged from student submitted PDF version of thesis.<br>Includes bibliographical references.<br>Monolayer patterns of block copolymer (BCP) microdomains have been pursued for applications in below sub-30 nm nanolithography. BCP selfassembly processing is scalable and low cost, and is well-suited for integration with existing semiconductor fabrication techniques. The two critical issues are how to obtain reliable long-range ordering of features with minimum defect densities and how to successfully transfer the patterns into other functional materials. Exceptionally well-ordered and robust nanoscale patterns can be made from poly(styrene-b-dimethylsiloxane) (PS-PDMS) BCPs, which have a very large Flory-Huggins interaction parameter between the blocks compared to other commonly used BCPs. Cylinder- or sphere-forming BCP films were spincoated over silicon substrates patterned with shallow steps using optical lithography or nanoscale posts made by electron-beam lithography, and solvent-annealed to induce ordering. This generates patterns with a correlation length of at least several micrometers. The annealed film was treated with plasma to obtain oxidized PDMS patterns with a lateral dimension of 14 - 18 nm. These can be used as an etch mask or an easily removable template for patterning functional materials. Solvent vapor treatments can tune the pattern dimension and morphology. Different degrees of solvent uptake in BCP films during solvent-annealing can manipulate the interfacial interaction between the two blocks, and a mixed solvent vapor can change the effective volume fraction of each block. The self-assembled patterns can be transferred into various kinds of functional materials.<br>(cont.) For example, arrays of parallel lines were used as a mask to pattern poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) conducting polymer thin films. The resulting PEDOT:PSS nanowire array was used as an chemiresistive-type ethanol-sensing device. Metallic films such as Ti, Pt, Ta, W, and magnetic Co and Ni were structured using a pattern-reversal process. Coercivity enhancements were observed for the fabricated ferromagnetic nanostructures such as wires, rings, and antidots. These functional nanostructures can be utilized for a variety of devices such as high-density and high performance sensor or memory devices.<br>by Yeon Sik Jung.<br>Ph.D.

Biocompatible and biodegradable poly(lactide)-2-methacryloyloxyethyl phosphorylcholine (PLA-PMPC) amphiphilic block copolymers were synthesized by a combination of Ring Opening Polymerization (ROP) and Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization techniques. The PLA-macroRAFT agent was synthesized by the derivatization of PLA-OH with RAFT agent 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPADB) achieving high levels of functionalization and narrow weight distributions (PDI range of 1.02-1.17). PLA-PMPC with varied MPC block lengths were synthesized yielding polymers with a narrow polydispersity PDI = 1.16-1.21. Triblock copolymers PMPC-PLA-PMPC with varying hydrophilic weight ratios were synthesized following an analogous method, the polymerizations were shown to be controlled with PDI’s of 1.24 and 1.36. PLA-PMPC block copolymers with varied compositions were self-assembled using several techniques to target different morphologies. Nanostructures were characterised by DLS and TEM. Block copolymers with a larger PLA block length were shown to generate smaller aggregates i.e. micelles. The morphologies observed for the various block copolymers were consistent amongst different preparative techniques. Vesicle structures were reproducible by the self-assembly of PMPC50-PLA51-PMPC50, however, by preparing nanoparticles by direct dissolution micelles formed. The block copolymers were shown to encapsulate a hydrophobic dye in aqueous media thereby demonstrating its potential drug delivery applications.

Il drug delivery attira molto interesse a causa della necessità di migliorare efficienza e selettività delle terapie farmacologiche. Capsule polimeriche per i farmaci sono una strategia promettente per prolungarne i tempi di circolazione, migliorarne il trasporto nel sangue, e modularne nel tempo il rilascio. In questo ambito, l’organizzazione spontanea dei copolimeri a blocchi (CB) in nanoparticelle (NP) compartimentalizzate in ambiente acquoso è uno strumento potente per la fabbricazione di sistemi per il drug delivery. In questa tesi vengono investigati la sintesi e l’autoassemblaggio (AS) controllati di una serie di CB anfifilici contenenti blocchi idrofilici biocompatibili e biomimetici. Nel Cap. 3 viene presentato un quadro completo del comportamento di AS di PS-b-PDMA in H2O da DMF. E’ stato preparato un set di campioni con pesi molecolari compresi fra 10 kDa e 57 kDa e fPDMA comprese fra 0.06 e 0.75, e le NP sono state caratterizzate con DLS, TEM, CEM, CET, SEM e AFM. Viene proposta una mappa morfologica, dove le morfologie dominanti sono state correlate con la caratteristiche chimiche dei CB. In particolare, quando fPDMA < 0.15, è stata osservata la formazione di particelle porose con diametri fino ad alcuni micron che assumono una fase spugnosa, stabile alla liofilizzazione. Nel Cap. 4, una serie di CB biocompatibili e biodegradabili di PEO-b-PLA sono stati sintetizzati tramite ROP controllata di lattide catalizzata da DBU. Il focus di ricerca era sull’effetto del solvente non selettivo sull’AS: NP ottenute da ACT, DX, THF e DMF sono state analizzate con DLS, CEM e CET. Dimensioni e PDI aumentavano nell’ordine ACT < DX < THF ~ DMF. Le NP sono state classificate in tre cluster: micelle (piccolo raggio, basso PDI), polimersomi (medio raggio, medio PDI), e micelle composte (grande raggio, grande PDI). Mentre ACT e DX portano alla formazione preferenziale di micelle, il THF permette di accedere a uno spazio morfologico molto più ampio. Infine, la DMF favorisce fenomeni di aggregazione di secondo ordine. Nel Cap. 5 vengono valutati la sintesi controllata, la funzionalizzazione terminale e la formazione di di- e triblocchi di polimeri a base di PEtOx biocompatibile tramite una combinazione di ROP e RAFT. Un blocco di PEtOx25 è stato sintetizzato con successo tramite CROP di 2-etil-2-ossazolina con buon controllo; è stato poi usato come macroCTA per la polimerizzazione sequenziale di Sty e t-BA per ottenere il copolimero a tre blocchi PEtOx-b-PS-b-PtBA. Vengono presentati risultati preliminari sul SA in etanolo come solvente selettivo per i blocchi di PEtOx e PtBA, ma non PS. Nel Cap. 6 è stato studiato l’effetto morfogenico di ACT, DX e DMF sul SA di PS-b-PDMA e PEO-b-PLA usando il rotore molecolare AzeNaph-1 come sonda di viscosità per il monitoraggio in situ dell’aggregazione dei CB. L’evoluzione della viscosità in funzione del contenuto di H2O in PS-b-PDMA è simile sia in DMF che DX: all’aggiunta di H2O, le catene di PS collassano rapidamente, formando core prevalentemente vetrosi. Coerentemente, il DLS mostra poca variazione di dimensioni delle NP fra i due solventi. Anche PEO-b-PLA forma domini vetrosi in DMF/H2O, ma non in ACT o DX. Al contrario, la viscosità locale del core è molto minore in ACT e DX che in DMF su tutto il range di frazione di H2O, ed è dipendente dal tempo. Questa aumentata mobilità molecolare promuove la differenziazione delle NP formate. Infine, nel Cap. 7 viene esplorato l’AS indotto da polimerizzazione di CB anfifilici basati su glicopolimeri. Tre campioni di PAGA con DP = 25, 50 e 75 sono stati polimerizzati in H2O/MeOH tramite RAFT, con ottimo controllo. L’ottimizzazione delle condizioni di reazioni ha permesso di usare PAGA25 e PAGA50 come stabilizzanti e macroCTA per l’estensione di catena con BA in H2O/MeOH. Il controllo sulla polimerizzazione è stato basso, ma sono state ottenute NP sferiche, stabili e monodisperse.<br>Drug delivery is a trending topic in current research due to the need to improve therapeutic efficiency and selectivity. Polymeric encapsulants for drugs are a promising strategy to prolong circulation times, enhance hydrophobic drug transport through the blood stream, and modulate drug release over time. In this field, amphiphilic block copolymers’ (BCs) spontaneous organization in compartimentalized nanoparticles (NPs) in water is a powerful tool for the fabrication of drug delivery systems. In this Doctoral thesis, the controlled synthesis and self-assembly (S-A) of a series of amphiphilic BCs containing biocompatible, stealthy hydrophilic blocks were investigated. Controlled polymerization techniques were employed to prepare copolymers with narrow molecular weight distributions. In Chapter 3, a complete picture of the previously unreported S-A behaviour of PS-b-PDMA in water from DMF is drawn. A comprehensive sample set spanning molecular weights from 10 kDa to 57 kDa and hydrophilic volume fractions fPDMA from 0.06 to 0.75 was prepared by sequential RAFT, and NPs were characterized by DLS, TEM, CEM, CET, SEM, and AFM. A morphology map is proposed, where predominant morphologies were correlated with BC chemical characteristics. In particular, stable hollow particles with diameters up to several microns when fPDMA drops below 0.15 are formed. Micron-large porous particles exhibiting a sponge phase which can withstand lyophilisation were observed. In Chapter 4, a series of biocompatible and biodegradable PEO-b-PLA BCs were synthesized by controlled ROP of lactide catalyzed by non-toxic DBU. The research focus was on the effect of the non-selective solvent on S-A: NPs obtained from ACT, DX, THF, DMF were analyzed by DLS, CEM and CET. Both size and PDI increased in the order ACT < DX < THF ~ DMF. NPs were classified into three clusters, labeled micelles (small size, low PDI), polymersomes (medium size, medium-low PDI) and large compound micelles (large size, large PDI). While ACT and DX yielded mostly micelles, THF allowed to access a much broader morphological space. Finally, DMF favoured second-order aggregation phenomena. In Chapter 5, controlled synthesis, chain-end functionalization and di- and triblock formation of biocompatible PEtOx-based polymers by a combination of ROP and RAFT techniques were evaluated. Biocompatible PEtOx25 blocks were successfully synthesized by CROP of 2-ethyl-2-oxazoline with good control. PEtOx25 was used as a macroCTA for the sequential polymerization of a Sty and tBA to yield a PEtOx25-b-PS50-b-PtBA25 triblock copolymer. Preliminary results on S-A in ethanol as a selective solvent for both PEtOx and PtBA, but not for PS, are presented. In Chapter 6, the morphogenic effect of ACT, DX and DMF on PS-b-PDMA and PEO-b-PLA S-A was studied using molecular rotor AzeNaph-1 as a local viscosity probe for the in situ monitoring of BC aggregation. Evolution of viscosity as a function of water content in PS-b-PDMA was similar both in DMF and DX: upon the addition of H2O, PS chains rapidly collapsed in NP cores, which were largely glassy. Consistently, DLS shows little variation on particle size between the two solvents. PEO113-b-PLAx also formed glassy domains in DMF/H2O, but not in ACT or DX. Contrarily, local core viscosity was much lower in ACT and DX than in DMF over the whole H2O fraction range, and was time-dependent. This increased chain mobility promoted the differentiation of NP formation. Finally, in Chapter 7, polymerization-induced S-A of glycopolymer-based amphiphilic BCs was investigated. Three PAGA samples with DP = 25, 50 and 75 were polymerized in H2O/methanol mixture by RAFT, with remarkable control. Optimization of reaction conditions allowed the use of PAGA25 and PAGA50 as stabilizers and macroCTAs for chain-extension with n-butylacrylate (BA) in methanol/H2O environment. Control on the polymerization was poor, but stable and monodisperse spherical NPs were obtained.