Martin A. Cole

Stimuli-responsive interfaces and systems for the control of protein-surface and cell-surface interactions

Real-time control over and reversibility of biomolecule-surface interactions at interfaces is an increasingly important goal for a range of scientific fields and applications. The field of stimuli-responsive, smart or switchable systems has generated much research interest due to its potential to attain unprecedented levels of control over biomolecule adsorption processes and interactions at engineered interfaces, including the control over reversibility of adsorption. Advances in this field are particularly relevant to applications in the areas of biosensing, chromatography, drug delivery and regenerative medicine. The control over biomolecule adsorption and desorption processes at interfaces is often used to control subsequent events such as cell-surface interactions. Considerable research interest has been directed at systems that can be reversibly switched between interacting and non-interacting states and used thus for switching, on and off, bio-interfacial interactions such as protein adsorption. Such switchable coatings often incorporate features such as temporal resolution, spatial resolution and reversibility. Here we review recent literature on switchable coatings that employ stimuli such as light, temperature, electric potential, pH and ionic strength to control protein adsorption/desorption and cell attachment/detachment en route to the development of next-generation smart bio-interfaces.

Stimulus-Responsiveness and Drug Release from Porous Silicon Films ATRP-Grafted with Poly(N-isopropylacrylamide)

In this report, we employ surface-initiated atom transfer radical polymerization (SI-ATRP) to graft a thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAM), of controlled thickness from porous silicon (pSi) films to produce a stimulus-responsive inorganic-organic composite material. The optical properties of this material are studied using interferometric reflectance spectroscopy (IRS) above and below the lower critical solution temperature (LCST) of the PNIPAM graft polymer with regard to variation of pore sizes and thickness of the pSi layer (using discrete samples and pSi gradients) and also the thickness of the PNIPAM coatings. Our investigations of the composites thermal switching properties show that pore size, pSi layer thickness, and PNIPAM coating thickness critically influence the materials thermoresponsiveness. This composite material has considerable potential for a range of applications including temperature sensors and feedback controlled drug release. Indeed, we demonstrate that modulation of the temperature around the LCST significantly alters the rate of release of the fluorescent anticancer drug camptothecin from the pSi-PNIPAM composite films.

Graphene: a multipurpose material for protective coatings

Graphene based materials have attracted great interest in the development of new and advanced protective coatings due to their excellent chemical resistance, impermeability to gases, adsorption capacity, anti-bacterial properties, mechanical strength, lubricity and thermal stability. This review presents current progress and discusses the major challenges and future potential of graphene in the field of protective coatings. This review specifically focuses on the most recent advances in the application of graphene for corrosion resistant coatings, flame retardant coatings, wear/scratch resistant coatings, anti-fouling coatings, pollutant adsorption coatings and anti-septic coatings.

Colloid probe AFM study of thermal collapse and protein interactions of poly(N-isopropylacrylamide) coatings

Graft coatings of poly(N-isopropylacrylamide) (pNIPAM) are of considerable interest for the reversible control of bio-interfacial interactions. In this study, graft coatings were prepared by free radical polymerisation from surface-bound polymerisable groups, on silicon wafers and quartz crystal microbalance (QCM) sensors. QCM with dissipation monitoring showed a gradual, extended phase change as the temperature increased. Colloid probe atomic force microscopy (CP-AFM) revealed a marked change in the compressibility of the coating below and above the lower critical solution temperature (LCST). Force curves showed an approximate 9-fold reduction in thickness between 24 °C and 38 °C, yet the collapsed coating at 38 °C still had a thickness significantly higher than the ellipsometrically determined dry thickness, indicating a residual extent of hydration above the LCST. At all temperatures, interaction force curves showed steric repulsion, though over different distances. There was little hysteresis between approach and retract force curves, which is evidence for almost instantaneous relaxation of the coating upon decompression. CP-AFM using a probe coated with bovine serum albumin (BSA) showed repulsive interactions with little approach/retraction hysteresis below the LCST, indicating lack of adhesion between the pNIPAM coating and the BSA-coated probe. In contrast, above the LCST the force curves on retraction were characteristic of adhesion, while the approach curves were still repulsive, and the adhesion increased in strength as the temperature was increased further beyond the LCST. Thus, QCM-D and CP-AFM data correlated well in showing a gradual nature of the phase transition and a concomitant gradual change in the interaction force with BSA.

Time-of-Flight-Secondary Ion Mass Spectrometry Study of the Temperature Dependence of Protein Adsorption onto Poly(N-isopropylacrylamide) Graft Coatings

Stimuli-responsive materials show considerable promise for applications that require control over biomolecule interactions at solid material interfaces. Graft coatings of poly(N-isopropylacrylamide) (pNIPAM) are of interest for biomedical and biotechnological applications due to their temperature-dependent switching of surface properties between adhesive and nonadhesive states for cells and proteins. The characterization of protein adsorption to these switchable coatings is a formidable task since switching not only influences the affinity for proteins but at the same time induces a significant change in the coating. Here, the highly sensitive analytical technique of time-of-flight-secondary ion mass spectrometry (TOF-SIMS) combined with principal component analysis (PCA) was used for the characterization of protein adsorption onto pNIPAM coatings prepared by free radical polymerization onto surface-bound polymerizable groups. Adsorption of bovine serum albumin and lysozyme onto pNIPAM coatings from phosphate buffered solutions was investigated at temperatures above and below the polymers lower critical solution temperature (LCST). Below the LCST, no adsorbed proteins could be detected even with this ultrasensitive method. Whereas above the LCST, adsorbed protein was detected in amounts corresponding at less than the monolayer. PCA loadings plots showed that adventitious contaminants, which might lead to confounding or misleading spectral changes upon protein exposure, were not observed.

Electro-induced protein deposition on low-fouling surfaces

Control over protein adsorption is a key issue for numerous biomedical applications ranging from diagnostic microarrays to tissue-engineered medical devices. Here, we describe a method for creating surfaces that prevent non-specific protein adsorption, which upon application of an external trigger can be transformed into surfaces showing high protein adsorption on demand. Silicon wafers were used as substrate materials upon which thin functional coatings were constructed by the deposition of an allylamine plasma polymer followed by high-density grafting of poly(ethylene oxide) aldehyde, resulting in a low-fouling surface. When the underlying highly doped silicon substrate was used as an electrode, the resulting electrostatic attraction between the electrode and charged proteins in solution induced protein deposition at the low-fouling interface. X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were used to characterize the surface modifications. Controlled protein adsorption experiments were carried out using horseradish peroxidase. The amount of protein deposited at the surface was then investigated by means of a colorimetric assay. It is expected that the concept described here will find use in a variety of biotechnological and biomedical applications, particularly in the area of biochips.

Control over wettability via surface modification of porous gradients

The control over surface wettability is of concern for a number of important applications including chromatography, microfluidics, biomaterials, low-fouling coatings and sensing devices. Here, we report the ability to tailor wettability across a surface using lateral porous silicon (pSi) gradients. Lateral gradients made by anodisation of silicon using an asymmetric electrode configuration showed a lateral distribution of pore sizes, which decreased with increasing distance from the electrode. Pore sizes were characterised using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Pore diameters ranged from micrometres down to less than 10 nanometres. Chemical surface modification of the pSi gradients was employed in order to produce gradients with different wetting or non-wetting properties. Surface modifications were achieved via silanisation of oxidised pSi surfaces introducing functionalities including polyethylene glycol, terminal amine and fluorinated hydrocarbon chains. Surface modifications were characterised using infrared spectroscopy. Sessile drop water contact angle measurements were used to probe the wettability in regions of different pore size across the gradient. For the fluorinated gradients, a comparison of equilibrium and dynamic contact angle measurement was undertaken. The fluorinated surface chemistry produced gradients with wettabilities ranging from hydrophobic to near super-hydrophobic whereas pSi gradients functionalised with polyethylene glycol showed graded hydrophilicity. In all cases investigated here, changes in pore size across the gradient had a significant effect on wettability.

Functionalized three-dimensional (3D) graphene composite for high efficiency removal of mercury

The synthesis of a thiol-functionalized graphene composite with a unique three-dimensional porous structure composed of graphene nanosheets decorated with αFeOOH and porous silica microparticles (diatomaceous earth) is presented. The performance of this material for the removal of mercury ions (Hg2+) from water is evaluated using a batch adsorption and membrane separation approach. An outstanding adsorption performance of >800 mg g−1 (at 400 mg L−1 Hg2+) was demonstrated significantly exceeding currently available benchmark adsorbents. An excellent adsorption performance was confirmed for the efficient (~100%) removal of a low (4 mg L−1) and high (120 mg L−1) concentration of Hg in real water samples using this composite in the form of membranes. The results indicate the versatility of the developed composite to be used in different forms for several water purification scenarios (batch, column, membranes) relevant for both drinking and wastewater treatments. Based on their outstanding performance, low cost, and simple and scalable preparation, the presented 3D graphene composites have a considerable potential for the development of efficient and cost-competitive adsorbents and membranes for environmental applications.

Switchable coatings for biomedical applications

The control over protein adsorption is of major importance for a variety of biomedical applications from diagnostic assays to tissue engineered medical devices. Most research has focused on the prevention of non-specific protein adsorption on solid substrates. Examples for surface modifications that significantly reduce protein adsorption include the grafting of polyacrylamide, poly (ethylene oxide) and polysaccharides. Here, we describe a method for creating surfaces that prevent non-specific protein adsorption, which in addition can be transformed into surfaces showing high protein adsorption on demand. Doped silicon wafers were used as substrate materials. Coatings were constructed by deposition of allylamine plasma polymer. The subsequent grafting of poly (ethylene oxide) aldehyde resulted in a surface with low protein fouling character. When the conductive silicon wafer was used as an electrode, the resulting field induced the adsorption of selected proteins. Surface modifications were analysed by X-ray photoelectron spectroscopy and atomic force microscopy. The controlled adsorption of proteins was investigated using a colorimetric assay to test enzymatic activity. The method described here represents an effective tool for the control over protein adsorption and is expected to find use in a variety of biomedical applications particularly in the area of biochips.