Electrochemical Diffusion Study in Poly(Ethylene Glycol) Dimethacrylate-Based Hydrogels.

Hydrogels are of great importance for functionalizing sensors and microfluidics, and poly(ethylene glycol) dimethacrylate (PEG-DMA) is often used as a viscosifier for printable hydrogel precursor inks. In this study, 1-10 kDa PEG-DMA based hydrogels were characterized by gravimetric and electrochemical methods to investigate the diffusivity of small molecules and proteins. Swelling ratios (SRs) of 14.43-9.24, as well as mesh sizes ξ of 3.58-6.91 nm were calculated, and it was found that the SR correlates with the molar concentration of PEG-DMA in the ink (MCI) (SR = 0.1127 × MCI + 8.3256, R2 = 0.9692) and ξ correlates with the molecular weight (Mw) (ξ = 0.3382 × Mw + 3.638, R2 = 0.9451). To investigate the sensing properties, methylene blue (MB) and MB-conjugated proteins were measured on electrochemical sensors with and without hydrogel coating. It was found that on sensors with 10 kDa PEG-DMA hydrogel modification, the DPV peak currents were reduced to 92 % for MB, 73 % for MB-BSA, and 23 % for MB-IgG. To investigate the diffusion properties of MB(-conjugates) in hydrogels with 1-10 kDa PEG-DMA, diffusivity was calculated from the current equation. It was found that diffusivity increases with increasing ξ. Finally, the release of MB-BSA was detected after drying the MB-BSA-containing hydrogel, which is a promising result for the development of hydrogel-based reagent reservoirs for biosensing.

Development and Characterization of Passivation Methods for Microneedle-based Biosensors.

Microneedles (MN) are short, sharp structures that have the ability to painlessly pierce the stratum corneum, the outermost layer of the skin, and interface with the dermal interstitial fluid that lies beneath. Because the interstitial fluid is rich in biomarkers, microneedle-based biosensors have the potential to be used in a wide range of diagnostic applications. To act as an electrochemical sensor, the tip or the body of the MN must be functionalized, while the substrate areas are generally passivated to block any unwanted background interference that may occur outside of the skin. This work presents four different passivation techniques, based on the application of SiO2, polymethyl methacrylate (PMMA), an adhesive film, and varnish to the substrate areas. Optical, SEM and electrochemical measurements were performed to quantitatively assess the performance of each film. The data shows that whilst manual application of varnish provided the highest level of electrical isolation, the spin-coating of a 5 µm thick layer of PMMA is likely to provide the best combination of performance and manufacturability. Clinical Relevance- Substrate passivation techniques will improve the performance of microneedle-based non-invasive continuous monitoring systems.

Influence of Grafted Block Copolymer Structure on Thermoresponsiveness of Superparamagnetic Core-Shell Nanoparticles.

The morphology and topology of thermoresponsive polymers have a strong impact on their responsive properties. Grafting onto spherical particles has been shown to reduce responsiveness and transition temperatures; grafting of block copolymers has shown that switchable or retained wettability of a surface or particle during desolvation of one block can take place. Here, doubly thermoresponsive block copolymers were grafted onto spherical, monodisperse, and superparamagnetic iron oxide nanoparticles to investigate the effect of thermal desolvation on spherical brushes of block copolymers. By inverting the block order, the influence of core proximity on the responsive properties of the individual blocks could be studied as well as their relative influence on the nanoparticle colloidal stability. The inner block was shown to experience a stronger reduction in transition temperature and transition enthalpy compared to the outer block. Still, the outer block also experiences a significant reduction in responsiveness due to the restricted environment in the nanoparticle shell compared to that of the free polymer state. The demonstrated pronounced distance dependence importantly implies the possibility, but also the necessity, to radially tailor polymer hydration transitions for applications such as drug delivery, hyperthermia, and biotechnological separation for which thermally responsive nanoparticles are being developed.

The Role of Chain Molecular Weight and Hofmeister Series Ions in Thermal Aggregation of Poly(2-Isopropyl-2-Oxazoline) Grafted Nanoparticles.

Thermoresponsive nanoparticles are promising smart materials for many applications. However, a rational design for applications requires a deeper understanding and experimental verification of the various parameters that influence the thermoresponsiveness of the spherical polymer brushes that define most of such nanomaterials. Therefore, we investigate superparamagnetic iron oxide nanoparticles (SPION) grafted with poly(2-isopropyl-2-oxazoline) (6⁻33 kg mol-1) by temperature-cycled dynamic light scattering and differential scanning calorimetry. The grafting of dense spherical polymer brushes leads to lower aggregation temperatures and transition enthalpies when compared with the free polymer. The transition enthalpy and temperature depend on the polymer shell size and structure. The addition of kosmotropic salts decreases the aggregation temperature following the Hofmeister series.

Crosslinking of floating colloidal monolayers.

ABSTRACT: Crosslinked colloidal monolayers are promising as templates, lithographic masks, filtration membranes, or membranes for controlled release rates in drug delivery. We demonstrate assembly of monodisperse micron-sized polystyrene (PS) beads at an air/water interface, which are transformed into crystalline monolayers using addition of surface-active agents. Vapor annealing methods with solvents (toluene and xylene) and crosslinking agents (divinylbenzene) were investigated regarding their ability to crosslink these floating monolayers directly at the interface, generating crosslinked membranes with crystal size up to 44 cm2, domain size up to 1.9 mm2, and nano-sized pores (100-300 nm). The demonstrated fabrication method emphasizes short fabrication time using a simple setup.

Aggregation of thermoresponsive core-shell nanoparticles: Influence of particle concentration, dispersant molecular weight and grafting.

Thermoresponsive core-shell nanoparticles represent an interesting class of materials with a triggered solubility transition. However, depending on the system, their aggregation behavior above the lower critical solution temperature (LCST) is ambiguous and obviously linked to a multitude of parameters. The induced aggregation of a set of well characterized poly(N-isopropylacrylamide)-nitrodopamine grafted superparamagnetic iron oxide nanoparticles is investigated with respect to the PNIPAM molecular weight (5-30kDa) and concentration using differential scanning calorimetry and temperature-cycled dynamic light scattering measurements. PNIPAM molecular weight clearly influences the thermoresponsiveness of the material, including LCST, colloidal aggregation and deaggregation as well as transition enthalpy. Furthermore, a strong impact of topology (grafted vs. free polymer chain) on the thermoresponsiveness is observed. Cluster size above the LCST depends on concentration and PNIPAM molecular weight. This makes it reasonable to conduct aggregation experiments under constant (high) particle molar concentration for comparative studies. Similarly, low particle molar concentration is used to elucidate individual particle shell properties by avoiding masking inter-particle effects.

Controlled aggregation and cell uptake of thermoresponsive polyoxazoline-grafted superparamagnetic iron oxide nanoparticles.

Hydrophilic polymer-coated iron oxide nanoparticles are potential materials for a plethora of applications in the biotechnological field. Typical such polymers, e.g. dextran or poly(ethylene glycol), lack the ability to tailor the biological response to an environmental trigger, while common responsive polymers such as poly(N-isopropylacrylamide) or poly(acrylic acid) are not suitable for biomedical applications. We present the synthesis and characterization of superparamagnetic iron oxide nanoparticles with thermoresponsive polyoxazoline brushes grafted at unprecedented density using nitrodopamine anchor chemistry. Reversible aggregation/deaggregation is observed in water and biological medium, confirming control over the colloidal stability. Thermal switching of the solubility could only be achieved by global heating of the sample, while local magnetothermal heating did not produce a sufficiently strong temperature gradient through the brush. Varying the polymer composition allows for tuning of the lower critical solution temperature (LCST) as well as the average nanoparticle cluster size obtained upon heating. The LCST of polyoxazolines and the thermal colloidal stability are shown to be greatly affected by ion concentration, by polymer grafting density and also by the presence of serum protein; this shows that transition temperatures of free polymers in water can be very misleading for the design of polymer-coated nanomaterials for biomedical applications. Finally, the thermoresponsive SPION are shown to be non-cytotoxic and with a low cell uptake scaling with the hydration of the polymer brush, which is tuned by the polymer composition. Thus, we demonstrate that pozylated nanoparticles provide the advantages of PEG- and PNIPAM-grafted nanoparticles, but provide a tunable and more easily functionalizable platform for further development.

Triggered Release from Thermoresponsive Polymersomes with Superparamagnetic Membranes.

Magnetic polymersomes were prepared by self-assembly of the amphiphilic block copolymer poly(isoprene-b-N-isopropylacrylamide) with monodisperse hydrophobic superparamagnetic iron oxide nanoparticles (SPION). The specifically designed thermoresponsive block copolymer allowed for efficient incorporation of the hydrophobic nanoparticles in the membrane core and encapsulation of the water soluble dye calcein in the lumen of the vesicles. Magnetic heating of the embedded SPIONs led to increased bilayer permeability through dehydration of the thermoresponsive PNIPAM block. The entrapped calcein could therefore be released in controlled doses solely through exposure to pulses of an alternating magnetic field. This hybrid SPION-polymersome system demonstrates a possible direction for release applications that merges rational polymersome design with addressed external magnetic field-triggered release through embedded nanomaterials.

Synthesis and Magneto-Thermal Actuation of Iron Oxide Core-PNIPAM Shell Nanoparticles.

Superparamagnetic nanoparticles have been proposed for many applications in biotechnology and medicine. In this paper, it is demonstrated how the excellent colloidal stability and magnetic properties of monodisperse and individually densely grafted iron oxide nanoparticles can be used to manipulate reversibly the solubility of nanoparticles with a poly(N-isopropylacrylamide)nitrodopamine shell. "Grafting-to" and "grafting-from" methods for synthesis of an irreversibly anchored brush shell to monodisperse, oleic acid coated iron oxide cores are compared. Thereafter, it is shown that local heating by magnetic fields as well as global thermal heating can be used to efficiently and reversibly aggregate, magnetically extract nanoparticles from solution and spontaneously redisperse them. The coupling of magnetic and thermally responsive properties points to novel uses as smart materials, for example, in integrated devices for molecular separation and extraction.

Melt-grafting for the synthesis of core-shell nanoparticles with ultra-high dispersant density.

Superparamagnetic iron oxide nanoparticles (NPs) are used in a rapidly expanding number of applications in e.g. the biomedical field, for which brushes of biocompatible polymers such as poly(ethylene glycol) (PEG) have to be densely grafted to the core. Grafting of such shells to monodisperse iron oxide NPs has remained a challenge mainly due to the conflicting requirements to replace the ligand shell of as-synthesized NPs with irreversibly bound PEG dispersants. We introduce a general two-step method to graft PEG dispersants from a melt to iron oxide NPs first functionalized with nitrodopamine (NDA). This method yields uniquely dense spherical PEG-brushes (∼3 chains per nm(2) of PEG(5 kDa)) compared to existing methods, and remarkably colloidally stable NPs also under challenging conditions.