Sacha Noimark

The role of surfaces in catheter-associated infections

In this critical review the biocidal efficacies of a variety of antimicrobial coatings currently in use for catheter surfaces are discussed to formulate the best strategy for decreasing the risk of catheter-associated infections. The development of new coatings containing antimicrobial chemicals and light-activated antimicrobial agents, and their applicability for use in catheters are summarised (132 references).

Incorporation of methylene blue and nanogold into polyvinyl chloride catheters; a new approach for light-activated disinfection of surfaces

Methylene blue and 2 nm gold nanoparticles were incorporated into commercial PVC catheters by use of a simple “swell–encapsulation–shrink” method using acetone–water mixtures. Neither the methylene blue nor the nanogold leached into aqueous solution and the assemblage was stable to photodegradation upon laser irradiation. Exposure of the modified catheters to red laser light for 4–8 minutes induced the lethal photosensitisation of Staphylococcus epidermidis and Escherichia coli. Results from time-resolved EPR spectroscopy suggested that enhanced methylene blue triplet state production occurs in the presence of 2 nm gold nanoparticles. The implication being that the levels of reactive oxygen species are higher in these co-doped materials than with methylene blue alone.

Light-activated antimicrobial surfaces with enhanced efficacy induced by a dark-activated mechanism

Novel bactericidal surfaces were prepared by incorporating crystal violet, methylene blue and 2 nm gold nanoparticles into medical grade silicone using a simple dipping technique. The modified polymers were stable to cleaning by use of an alcohol-based wipe and demonstrated good photostability under intense illumination conditions. The photobactericidal activity of this polymer was compared against a range of other photobactericidal polymers against both Staphylococcus epidermidis and Escherichia coli, under white lighting conditions comparable to that found in a clinical environment. Not only did this novel multi-dye–nanogold–polymer exhibit the strongest photobactericidal activity reported to date, surprisingly, it also demonstrated significant antimicrobial activity under dark conditions.

Photobactericidal polymers; the incorporation of crystal violet and nanogold into medical grade silicone

Crystal violet and 2 nm gold nanoparticles were incorporated into medical grade silicone polymers by use of a novel two-step dipping strategy using water and water–acetone mixtures. Optical microscopic examination showed that the optimised polymer incorporated dye close to the polymer surface, with minimal dye encapsulation throughout the polymer bulk. The modified polymer was stable under aqueous conditions with negligible leaching of crystal violet from the polymer into surrounding aqueous solution at 37 °C. Exposure of the modified silicone to low power 635 nm laser light induced the lethal photosensitisation of both Staphylococcus epidermidis and Escherichia coli. Despite the laser used not matching the absorption maximum of the crystal violet-containing silicone samples, the lethal photosensitisation was the highest reported, in terms of bacterial kill per energy dose. Furthermore, surprisingly, some statistically significant dark kill was also noted.

Potent Antibacterial Activity of Copper Embedded into Silicone and Polyurethane.

A simple, easily up-scalable swell-encapsulation-shrink technique was used to incorporate small 2.5 nm copper nanoparticles (CuNPs) into two widely used medical grade polymers, polyurethane, and silicone, with no significant impact on polymer coloration. Both medical grade polymers with incorporated CuNPs demonstrated potent antimicrobial activity against the clinically relevant bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. CuNP-incorporated silicone samples displayed potent antibacterial activity against both bacteria within 6 h. CuNP-incorporated polyurethane exhibited more efficacious antimicrobial activity, resulting in a 99.9% reduction in the numbers of both bacteria within just 2 h. With the high prevalence of hospital-acquired infections, the use of antimicrobial materials such as these CuNP-incorporated polymers could contribute to reducing microbial contamination associated with frequently touched surfaces in and around hospital wards (e.g., bed rails, overbed tables, push plates, etc.).

Photosensitisation studies of silicone polymer doped with methylene blue and nanogold for antimicrobial applications

Photosensitisation of polymers has important potential clinical applications such as the prevention of catheter-associated urinary tract infections (CAUTIs). Polymers incorporated with methylene blue (MB) and 2 nm gold nanoparticles (AuNPs) are effective in killing bacteria at the surface following low power visible illumination. Studies of medical-grade silicone polymer samples including segments from urinary catheters were carried out to investigate the generation of reactive oxygen species and the involvement of Type 1 and 2 mechanisms. Singlet oxygen was observed using direct phosphorescence detection and hydroxyl radical generation using electron paramagnetic resonance (EPR) spectroscopy; we conclude that both Type 1 and 2 mechanisms can operate with polymeric photosensitisation. Transmission electron microscopy (TEM) directly demonstrated the incorporation of AuNPs at the surface of the silicone. Using silicone doped with MB AuNPs, a ≥3 log10 reduction in the number of viable Staphylococcus epidermidis bacteria was achieved when exposed to low power laser light; prior sterilisation with ethylene oxide (EO) had no influence on efficacy.

Thiol-capped gold nanoparticles swell-encapsulated into polyurethane as powerful antibacterial surfaces under dark and light conditions

A simple procedure to develop antibacterial surfaces using thiol-capped gold nanoparticles (AuNPs) is shown, which effectively kill bacteria under dark and light conditions. The effect of AuNP size and concentration on photo-activated antibacterial surfaces is reported and we show significant size effects, as well as bactericidal activity with crystal violet (CV) coated polyurethane. These materials have been proven to be powerful antibacterial surfaces against both Gram-positive and Gram-negative bacteria. AuNPs of 2, 3 or 5 nm diameter were swell-encapsulated into PU before a coating of CV was applied (known as PU-AuNPs-CV). The antibacterial activity of PU-AuNPs-CV samples was tested against Staphylococcus aureus and Escherichia coli as representative Gram-positive and Gram-negative bacteria under dark and light conditions. All light conditions in this study simulated a typical white-light hospital environment. This work demonstrates that the antibacterial activity of PU-AuNPs-CV samples and the synergistic enhancement of photoactivity of triarylmethane type dyes is highly dependent on nanoparticle size and concentration. The most powerful PU-AuNPs-CV antibacterial surfaces were achieved using 1.0 mg mL−1 swell encapsulation concentrations of 2 nm AuNPs. After two hours, Gram-positive and Gram-negative bacteria were reduced to below the detection limit (>4 log) under dark and light conditions.

Pencil beam all-optical ultrasound imaging

A miniature, directional fibre-optic acoustic source is presented that employs geometrical focussing to generate a nearly-collimated acoustic pencil beam. When paired with a fibre-optic acoustic detector, an all-optical ultrasound probe with an outer diameter of 2.5 mm is obtained that acquires a pulse-echo image line at each probe position without the need for image reconstruction. B-mode images can be acquired by translating the probe and concatenating the image lines, and artefacts resulting from probe positioning uncertainty are shown to be significantly lower than those observed for conventional synthetic aperture scanning of a non-directional acoustic source. The high image quality obtained for excised vascular tissue suggests that the all-optical ultrasound probe is ideally suited for in vivo, interventional applications.

Through-needle all-optical ultrasound imaging in vivo : a preclinical swine study

High-frequency ultrasound imaging can provide exquisite visualizations of tissue to guide minimally invasive procedures. Here, we demonstrate that an all-optical ultrasound transducer, through which light guided by optical fibers is used to generate and receive ultrasound, is suitable for real-time invasive medical imaging in vivo. Broad-bandwidth ultrasound generation was achieved through the photoacoustic excitation of a multiwalled carbon nanotube-polydimethylsiloxane composite coating on the distal end of a 300-μm multi-mode optical fiber by a pulsed laser. The interrogation of a high-finesse Fabry–Pérot cavity on a single-mode optical fiber by a wavelength-tunable continuous-wave laser was applied for ultrasound reception. This transducer was integrated within a custom inner transseptal needle (diameter 1.08 mm; length 78 cm) that included a metallic septum to acoustically isolate the two optical fibers. The use of this needle within the beating heart of a pig provided unprecedented real-time views (50 Hz scan rate) of cardiac tissue (depth: 2.5 cm; axial resolution: 64 μm) and revealed the critical anatomical structures required to safely perform a transseptal crossing: the right and left atrial walls, the right atrial appendage, and the limbus fossae ovalis. This new paradigm will allow ultrasound imaging to be integrated into a broad range of minimally invasive devices in different clinical contexts.

A reconfigurable all-optical ultrasound transducer array for 3D endoscopic imaging

A miniature all-optical ultrasound imaging system is presented that generates three-dimensional images using a stationary, real acoustic source aperture. Discrete acoustic sources were sequentially addressed by scanning a focussed optical beam across the proximal end of a coherent fibre bundle; high-frequency ultrasound (156% fractional bandwidth centred around 13.5 MHz) was generated photoacoustically in the corresponding regions of an optically absorbing coating deposited at the distal end. Paired with a single fibre-optic ultrasound detector, the imaging probe (3.5 mm outer diameter) achieved high on-axis resolutions of 97 μm, 179 μm and 110 μm in the x, y and z directions, respectively. Furthermore, the optical scan pattern, and thus the acoustic source array geometry, was readily reconfigured. Implementing four different array geometries revealed a strong dependency of the image quality on the source location pattern. Thus, by employing optical technology, a miniature ultrasound probe was fabricated that allows for arbitrary source array geometries, which is suitable for three-dimensional endoscopic and laparoscopic imaging, as was demonstrated on ex vivo porcine cardiac tissue.