Making silicone rubber highly resistant to bacterial attachment using thiol-ene grafting

Biomedical devices are indispensable in modern medicine yet offer surfaces that promote bacterial attachment and biofilm formation, resulting in acute and chronic healthcare-associated infections. We have developed a simple method to graft acrylates to silicone rubber, polydimethylsiloxane (PDMS), a commonly used device material that is often colonized by bacteria. We demonstrate a novel method whereby nontoxic bacteria attachment-resistant polymers can be readily grafted from and grafted to the surface using thiol-ene chemistry, substantially reducing bacterial colonization. With use of this approach, bacterial biofilm coverage can be reduced by 99% compared with standard PDMS in an in vitro assay. This grafting approach offers significant advantages over commonly used physisorbed coatings, especially in areas of high shear or mechanical stress. Furthermore, the approach is versatile such that the grafted material properties can be tailored for the desired final application

Electrochemically stimulating developments in bioelectronic medicine

Cellular homeostasis is in part controlled by biological generated electrical activity. By interfacing biology with electronic devices this electrical activity can be modulated to actuate cellular behaviour. There are current limitations in merging electronics with biology sufficiently well to target and sense specific electrically active components of cells. By addressing this limitation, researchers give rise to new capabilities for facilitating the twoway transduction signalling mechanisms between the electronic and cellular components. This is required to allow significant advancement of bioelectronic technology which offers new ways of treating and diagnosing diseases. Most of the progress that has been achieved to date in developing bioelectronic therapeutics stimulate neural communication, which ultimately orchestrates organ function back to a healthy state. Some devices used in therapeutics include cochlear and retinal implants and vagus nerve stimulators. However, all cells can be effected by electrical inputs which gives rise to the opportunity to broaden the use of bioelectronic medicine for treating disease. Electronic actuation of non-excitable cells has been shown to lead to ‘programmed’ cell behaviour via application of electronic input which alter key biological processes. A neglected form of cellular electrical communication which has not yet been considered when developing bioelectronics therapeutics is faradaic currents. These are generated during redox reactions. A precedent of electrochemical technology being used to modulate these reactions thereby controlling cell behaviour has already been set. In this mini review we highlight the current state of the art of electronic routes to modulating cell behaviour and identify new ways in which electrochemistry could be used to contribute to the new field of bioelectronic medicine

Versatile routes to functional RAFT chain transfer agents through the Passerini multicomponent reaction

The widespread adoption of RAFT polymerization stems partly from the ease and utility of installing a functional chain transfer agent onto the ends of the generated polymer chains. In parallel, the Passerini multicomponent reaction offers great versatility in converting a wide range of easily accessible building blocks to functional materials. In this work, we have combined the two approaches such that a single, commonly available, RAFT agent is used in Passerini reactions to generate a variety of multifunctional RAFT chain transfer agents containing ester linkages. Reactions to generate the multifunctional RAFT agents took place under mild conditions and in good yields. The resulting Passerini-RAFT agents were able to exert control over radical polymerization to generate materials of well-defined molecular weights and dispersity. Furthermore, the presence in these polymer cores of ester and amide functionality through the Passerini chemistries, provided regions in the materials which are inherently biodegradable, facilitating any subsequent biomedical applications. The work overall thus demonstrates a versatile and facile synthetic route to multi functional RAFT chain transfer agents and biodegradable polymers

Multivariate ToF-SIMS image analysis of polymer microarrays and protein adsorption

The complexity of hyperspectral time of flight secondary ion mass spectrometry (ToF-SIMS) datasets makes their subsequent analysis and interpretation challenging, and is often an impasse to the identification of trends and differences within large sample-sets. The application of multivariate data analysis has become a routine method to successfully deconvolute and analyze objectively these datasets. The advent of high-resolution large area ToF-SIMS imaging capability has enlarged further the data handling challenges. In this work, a modified multivariate curve resolution image analysis of a polymer microarray containing 70 different poly(meth)acrylate type spots (over a 9.2 × 9.2 mm area) is presented. This analysis distinguished key differences within the polymer library such as the differentiation between acrylate and methacrylate polymers and variance specific to side groups. Partial least squares (PLS) regression analysis was performed to identify correlations between the ToF-SIMS surface chemistry and the protein adsorption. PLS analysis identified a number of chemical moieties correlating with high or low protein adsorption, including ions derived from the polymer backbone and polyethylene glycol side-groups. The retrospective validation of the findings from the PLS analysis was also performed using the secondary ion images for those ions found to significantly contribute to high or low protein adsorption

Tryptic digestion coupled with ambient DESI and LESA mass spectrometry enables identification of skeletal muscle proteins in mixtures and distinguishes between beef, pork, horse, chicken and turkey meat

The use of ambient desorption electrospray ionization (DESI-MS) mass spectrometry and liquid extraction surface analysis mass spectrometry (LESA-MS) is explored for the first time to analyse skeletal muscle proteins obtained from mixture of standard proteins and raw meat. Single proteins and mixtures of up to five proteins (myoglobin, troponin C, actin, BSA, tropomyosin) were deposited onto a polymer surface, followed by in-situ tryptic digestion and comparative analysis using DESI-MS and LESA-MS using tandem electrospray MS. Peptide peaks specific to individual proteins were readily distinguishable with good signal-to-noise ratio in the five-component mixture. LESA-MS gave a more stable analysis and greater sensitivity compared with DESI-MS. Meat tryptic digests were subjected to peptidomics analysis by DESI-MS and LESA-MS. Bovine, horse, pig, chicken and turkey muscle digests were clearly discriminated using multivariate data analysis (MVA) of the peptidomic datasets. The most abundant skeletal muscle proteins were identified and correctly classified according to the species following MS/MS analysis. The study shows, for the first time, that ambient ionization techniques such as DESI-MS and LESA-MS have great potential for species-specific analysis and differentiation of skeletal muscle proteins by direct surface desorption

High‐Throughput Miniaturized Screening of Nanoparticle Formation via Inkjet Printing

This is the peer reviewed version of the following article:Ioanna D. Styliari, et al, ‘High‐Throughput Miniaturized Screening of Nanoparticle Formation via Inkjet Printing’, Macromolecular Materials and Engineering, (2018), which has been published in final form at https://doi.org/10.1002/mame.201800146. Under embargo until 27 May 2019. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.The self‐assembly of specific polymers into well‐defined nanoparticles (NPs) is of great interest to the pharmaceutical industry as the resultant materials can act as drug delivery vehicles. In this work, a high‐throughput method to screen the ability of polymers to self‐assemble into NPs using a picoliter inkjet printer is presented. By dispensing polymer solutions in dimethyl sulfoxide (DMSO) from the printer into the wells of a 96‐well plate, containing water as an antisolvent, 50 suspensions are screened for nanoparticle formation rapidly using only nanoliters to microliters. A variety of polymer classes are used and in situ characterization of the submicroliter nanosuspensions shows that the particle size distributions match those of nanoparticles made from bulk suspensions. Dispensing organic polymer solutions into well plates via the printer is thus shown to be a reproducible and fast method for screening nanoparticle formation which uses two to three orders of magnitude less material than conventional techniques. Finally, a pilot study for a high‐throughput pipeline of nanoparticle production, physical property characterization, and cytocompatibility demonstrates the feasibility of the printing approach for screening of nanodrug delivery formulations. Nanoparticles are produced in the well plates, characterized for size and evaluated for effects on metabolic activity of lung cancer cells.Peer reviewe

Improved Constraints on the Preferential Heating and Acceleration of Oxygen Ions in the Extended Solar Corona

We present a detailed analysis of oxygen ion velocity distributions in the extended solar corona, based on observations made with the Ultraviolet Coronagraph Spectrometer (UVCS) on the SOHO spacecraft. Polar coronal holes at solar minimum are known to exhibit broad line widths and unusual intensity ratios of the O VI 1032, 1037 emission line doublet. The traditional interpretation of these features has been that oxygen ions have a strong temperature anisotropy, with the temperature perpendicular to the magnetic field being much larger than the temperature parallel to the field. However, recent work by Raouafi and Solanki suggested that it may be possible to model the observations using an isotropic velocity distribution. In this paper we analyze an expanded data set to show that the original interpretation of an anisotropic distribution is the only one that is fully consistent with the observations. It is necessary to search the full range of ion plasma parameters to determine the values with the highest probability of agreement with the UVCS data. The derived ion outflow speeds and perpendicular kinetic temperatures are consistent with earlier results, and there continues to be strong evidence for preferential ion heating and acceleration with respect to hydrogen. At heliocentric heights above 2.1 solar radii, every UVCS data point is more consistent with an anisotropic distribution than with an isotropic distribution. At heights above 3 solar radii, the exact probability of isotropy depends on the electron density chosen to simulate the line-of-sight distribution of O VI emissivity. (abridged abstract)Comment: 19 pages (emulateapj style), 13 figures, ApJ, in press (v. 679; May 20, 2008

Ambient DESI and LESA-MS analysis of proteins adsorbed to a biomaterial surface using in-situ surface tryptic digestion

The detection and identification of proteins adsorbed onto biomaterial surfaces under ambient conditions has significant experimental advantages but has proven to be difficult to achieve with conventional measuring technologies. In this study, we present an adaptation of desorption electrospray ionization (DESI) and liquid extraction surface analysis (LESA) mass spectrometry (MS) coupled with in-situ surface tryptic digestion to identify protein species from a biomaterial surface. Cytochrome c, myoglobin, and BSA in a combination of single and mixture spots were printed in an array format onto Permanox slides, followed by in-situ surface digestion and detection via MS. Automated tandem MS performed on surface peptides was able to identify the proteins via MASCOT. Limits of detection were determined for DESI-MS and a comparison of DESI and LESA-MS peptide spectra characteristics and sensitivity was made. DESI-MS images of the arrays were produced and analyzed with imaging multivariate analysis to automatically separate peptide peaks for each of the proteins within a mixture into distinct components. This is the first time that DESI and LESA-MS have been used for the in-situ detection of surface digested proteins on biomaterial surfaces and presents a promising proof of concept for the use of ambient MS in the rapid and automated analysis of surface proteins

Development, printability and post-curing studies of formulations of materials resistant to microbial attachment for use in inkjet based 3D printing

Purpose: This paper aims to print 3D structures from polymers that resist bacterial attachment by reactive jetting of acrylate monomers. Design/methodology/approach: The first step towards printing was ink development. Inks were characterised to carry out an estimation of their potential printability using the Z parameter to predict stable jetting conditions. Printability conditions were optimised for each ink using a Dimatix DMP-2800, which enabled 3D structures to be fabricated. Findings: UV photo-initiated polymers, which resist bacterial attachment, were found to be printable using piezo-based inkjet printers. The waveform required for each ink depends on the value of the Z parameter. Once the waveform and the printability parameters were optimised, 3D objects were fabricated. Research limitations/implications: This methodology has been confirmed as an effective method to 3D print materials that have been demonstrated to be bacteria resistant. However, ink curing depends on modification of some parameters (such as photoinitiator concentration or UV exposure time) which would result in an improvement of the curing process post jetting. Social implications: The combination of inkjet based 3D printing with new materials resistant to bacterial attachment means the possibility of building customised medical devices with a high level of complexity and bespoke features can be fully realised. The scope and variability of the devices produced will exceed what can be achieved using standard fabrication methodologies and can be applied to reduce the incidence of device associated infections and to address increased morbidity, mortality and health care costs associated with nosocomial infections. Originality/value: In this paper, the novel use of materials that resist bacterial attachment has been described to build 3D structures using material jetting. Its value lies on the potential impact this methodology could produce in the biomedical device and research fields