Thomas H. Epps

Self-assembly of block copolymer thin films

Block copolymers self-assemble on nanometer length scales, making them ideal for emerging nanotechnologies. Many applications (e.g., templating, membranes) require the use of block copolymers in thin film geometries (∼100 nm thickness), where self-assembly is strongly influenced by surface energetics. In this review, we discuss the roles of surface and interfacial effects on self-assembly, with a specific focus on confinement, substrate surface modification, and thermal and solvent annealing conditions. Finally, we comment on novel techniques for manipulating and characterizing thin films, motivating the use of gradient and high-throughput methods for gaining a comprehensive picture of self-assembly to enable advanced nanotechnologies.

Stimuli-responsive copolymer solution and surface assemblies for biomedical applications

Stimuli-responsive polymeric materials is one of the fastest growing fields of the 21st century, with the annual number of papers published more than quadrupling in the last ten years. The responsiveness of polymer solution assemblies and surfaces to biological stimuli (e.g. pH, reduction-oxidation, enzymes, glucose) and externally applied triggers (e.g. temperature, light, solvent quality) shows particular promise for various biomedical applications including drug delivery, tissue engineering, medical diagnostics, and bioseparations. Furthermore, the integration of copolymer architectures into stimuli-responsive materials design enables exquisite control over the locations of responsive sites within self-assembled nanostructures. The combination of new synthesis techniques and well-defined copolymer self-assembly has facilitated substantial developments in stimuli-responsive materials in recent years. In this tutorial review, we discuss several methods that have been employed to synthesize self-assembling and stimuli-responsive copolymers for biomedical applications, and we identify common themes in the response mechanisms among the targeted stimuli. Additionally, we highlight parallels between the chemistries used for generating solution assemblies and those employed for creating copolymer surfaces.

Stimuli responsive materials

Dramatic developments in the burgeoning field of polymer science are enabling new materials designs, synthetic methods, functional architectures, and applications. Today’s polymers are finding utility in broad areas, ranging from everyday commodity plastics to emerging, specialized, and high-tech materials. Moreover, it is apparent that the continued development of polymeric systems will be facilitated by ever-increasing understanding of advanced polymer synthesis and characterization techniques. This enhanced toolbox and knowledge-base will foster the facile design of next-generation precision materials with predictable and changeable properties. The present themed issue focuses on recent developments in the design of polymers that change properties in response to a single stimulus or multiple stimuli. These so-called ‘smart’ or stimuliresponsive polymers represent a growing cadre of materials that support various applications (e.g., controlled release agents, responsive coatings, and adaptive shape memory materials). Stimuli-responsive materials have benefited from significant advances in polymer science in recent years, and this themed issue highlights several of the fascinating developments that could have a major impact on the implementation of new smart materials. To fully address the field of stimuli responsive polymers, first we must understand the breadth of available stimuli that can induce a desired response, then we must design the polymer functionalities and systems that enable such a response; finally, we must develop methods to characterize the macromolecular changes as a result of that response. As demonstrated in this issue, many of the interesting properties of responsive materials arise from a transition in solubility or conformation of a macromolecule in the presence of a solvent. In this manner, transitions at the molecular level can be amplified to result in a change in nanoscale structure and/or materials properties. Gibson and O’Reilly (DOI: 10.1039/C3CS60035A) overview these transitions in the specific area of thermoresponsive polymers with particular attention to the effect of nanoscale geometry on the resulting change in chain conformation following a temperature change. Sumerlin and co-workers (DOI: 10.1039/ C3CS35499G) also highlight temperatureresponsive polymers with particular emphasis on design parameters that facilitate tuning of the specific transition temperatures. Light-responsive materials have received significant attention, as discussed by Gohy and Zhao (DOI: 10.1039/ C3CS35469E) in a review focused on reversible and irreversible transitions of photoresponsive copolymer micelles. Further, many systems can be designed a Institute for Technical and Macromolecular Chemistry, University of Hamburg, Bundesstrasse 45, D-20146 Hamburg, Germany. E-mail: theato@chemie.uni-hamburg.de b George & Josephine Butler Polymer Research Laboratory, Department of Chemistry, University of Florida, Gainesville, FL 32611, USA. E-mail: sumerlin@chem.ufl.edu c Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK. E-mail: Rachel.OReilly@warwick.ac.uk d Department of Chemical & Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, DE 19716, USA. E-mail: thepps@udel.edu

Generating Thickness Gradients of Thin Polymer Films via Flow Coating

Thickness is a governing factor in the behavior of films and coatings. To enable the high-throughput analysis of this parameter in polymer systems, we detail the design and operation of a “flow coater” device for fabricating continuous libraries of polymer film thickness over tailored ranges. Focusing on the production of model polystyrene film libraries, we thoroughly outline the performance of flow coating by varying critical factors including device geometry, device motion, and polymer solution parameters.

Systematic Study on the Effect of Solvent Removal Rate on the Morphology of Solvent Vapor Annealed ABA Triblock Copolymer Thin Films

Nanoscale self-assembly of block copolymer thin films has garnered significant research interest for nanotemplate design and membrane applications. To fulfill these roles, control of thin film morphology and orientation is critical. Solvent vapor annealing (SVA) treatments can be used to kinetically trap morphologies in thin films not achievable by traditional thermal treatments, but many variables affect the outcome of SVA, including solvent choice, total solvent concentration/swollen film thickness, and solvent removal rate. In this work, we systematically examined the effect of solvent removal rate on the final thin film morphology of a cylinder-forming ABA triblock copolymer. By kinetically trapping the film morphologies at key points during the solvent removal process and then using successive ultraviolet ozone (UVO) etching steps followed by atomic force microscopy (AFM) imaging to examine the through-film morphologies of the films, we determined that the mechanism for cylinder reorientation from substrate-parallel to substrate-perpendicular involved the propagation of changes at the free surface through the film toward the substrate as a front. The degree of reorientation increased with successively slower solvent removal rates. Furthermore, the AFM/UVO etching scheme permitted facile real-space analysis of the thin film internal structure in comparison to cross-sectional transmission electron microscopy.

Gradient Solvent Vapor Annealing of Block Copolymer Thin Films Using a Microfluidic Mixing Device

Solvent vapor annealing (SVA) with solvent mixtures is a promising approach for controlling block copolymer thin film self-assembly. In this work, we present the design and fabrication of a solvent-resistant microfluidic mixing device to produce discrete SVA gradients in solvent composition and/or total solvent concentration. Using this device, we identified solvent composition dependent morphology transformations in poly(styrene-b-isoprene-b-styrene) films. This device enables faster and more robust exploration of SVA parameter space, providing insight into self-assembly phenomena.

A simple approach to characterizing block copolymer assemblies: graphene oxide supports for high contrast multi-technique imaging.

Block copolymers are well-known to self-assemble into a range of 3-dimensional morphologies. However, due to their nanoscale dimensions, resolving their exact structure can be a challenge. Transmission electron microscopy (TEM) is a powerful technique for achieving this, but for polymeric assemblies chemical fixing/staining techniques are usually required to increase image contrast and protect specimens from electron beam damage. Graphene oxide (GO) is a robust, water-dispersable, and nearly electron transparent membrane: an ideal support for TEM. We show that when using GO supports no stains are required to acquire high contrast TEM images and that the specimens remain stable under the electron beam for long periods, allowing sample analysis by a range of electron microscopy techniques. GO supports are also used for further characterization of assemblies by atomic force microscopy. The simplicity of sample preparation and analysis, as well as the potential for significantly increased contrast background, make GO supports an attractive alternative for the analysis of block copolymer assemblies.

Generation of Monolayer Gradients in Surface Energy and Surface Chemistry for Block Copolymer Thin Film Studies

We utilize a vapor deposition setup and cross-diffusion of functionalized chlorosilanes under dynamic vacuum to generate a nearly linear gradient in surface energy and composition on a silicon substrate. The gradient can be tuned by manipulating chlorosilane reservoir sizes and positions, and the gradient profile is independent of time as long as maximum coverage of the substrate is achieved. Our method is readily amenable to the creation of gradients on other substrate surfaces, due to the use of vapor deposition, and with other functionalities, due to our use of functionalized chlorosilanes. Our gradients were characterized using contact angle measurements and X-ray photoelectron spectroscopy. From these measurements, we were able to correlate composition, contact angle, and surface energy. We generated a nearly linear gradient with a range in mole fraction of one component from 0.15 to 0.85 (34 to 40 mJ/m(2) in surface energy) to demonstrate its utility in a block copolymer thin film morphology study. Examination of the copolymer thin film surface morphology with optical and atomic force microscopy revealed the expected morphological transitions across the gradient.

PEG-polypeptide block copolymers as pH-responsive endosome-solubilizing drug nanocarriers.

Herein we report the potential of click chemistry-modified polypeptide-based block copolymers for the facile fabrication of pH-sensitive nanoscale drug delivery systems. PEG–polypeptide copolymers with pendant amine chains were synthesized by combining N-carboxyanhydride-based ring-opening polymerization with post-functionalization using azide–alkyne cycloaddition. The synthesized block copolymers contain a polypeptide block with amine-functional side groups and were found to self-assemble into stable polymersomes and disassemble in a pH-responsive manner under a range of biologically relevant conditions. The self-assembly of these block copolymers yields nanometer-scale vesicular structures that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin at physiological pH but that fall apart spontaneously at endosomal pH levels after cellular uptake. When drug-encapsulated copolymer assemblies were delivered systemically, significant levels of tumor accumulation were achieved, with efficacy against the triple-negative breast cancer cell line, MDA-MB-468, and suppression of tumor growth in an in vivo mouse model.

Interfacial Manipulations: Controlling Nanoscale Assembly in Bulk, Thin Film, and Solution Block Copolymer Systems

Nanostructured soft materials from self-assembled block copolymers (BCP)s and polymer blends can enable the reliable, high-throughput, and cost-effective generation of nanoscale structural motifs for many emerging technologies. Our research group has studied the phase behavior of BCPs in bulk, thin film, and solution environments with a particular focus on using interfacial manipulations to control self-assembly and to access a vast array of nanoscale morphologies and orientations. These interfacial manipulations can be synthetic alterations that are directly incorporated into the BCP chain to modify polymer-polymer interactions, post-polymerization and non-synthetic modifications that affect block interactions, or changes to the polymer specimens external surroundings to control self-assembly in a confining environment. Herein, we describe methods that we have employed to manipulate BCP self-assembly for various application targets, and we discuss the key effects of such manipulations on the resulting nanoscale morphologies.