Alan O'Riordan

Tetrodotoxin: Chemistry, Toxicity, Source, Distribution and Detection

Tetrodotoxin (TTX) is a naturally occurring toxin that has been responsible for human intoxications and fatalities. Its usual route of toxicity is via the ingestion of contaminated puffer fish which are a culinary delicacy, especially in Japan. TTX was believed to be confined to regions of South East Asia, but recent studies have demonstrated that the toxin has spread to regions in the Pacific and the Mediterranean. There is no known antidote to TTX which is a powerful sodium channel inhibitor. This review aims to collect pertinent information available to date on TTX and its analogues with a special emphasis on the structure, aetiology, distribution, effects and the analytical methods employed for its detection.

Advanced photoresist technologies for microsystems

A growing interest in the development of high aspect ratio photoresists for micromachining microsystems (MST) products has resulted in the availability of a number of commercially available photoresist products. This paper describes in detail the applications of three such resists, namely EPON SU-8, Clariant AZ 4562 and the Shipley electroplated photoresist ED2100. Applications such as etch hard masks, micromoulds, severe topography coatings for metal interconnects and photoplastic mouldings are discussed, and novel examples are presented of where these resists are currently used in both telecomm and microfluidic markets. In particular, the versatility of the photoplastic negative resist EPON SU-8, which is used in a number of MST prototypes, is demonstrated. Future trends in resist technologies for MST are discussed.

Role of interleukin (IL-10) in probiotic-mediated immune modulation: an assessment in wild-type and IL-10 knock-out mice

While the impact of Bifidobacterium infantis 35624 and other probiotics on cytokines has been shown in established colitis, the effects of B. infantis consumption in pre‐inflammation of interleukin (IL)‐10 knock‐out (KO) mice and on the wild‐type (WT) C57Bl/6 mice have not been well demonstrated. The objective of this study was to examine cytokine responses in mucosal and systemic lymphoid compartments of IL‐10 KO mice early in disease and to compare with control WT mice. Mice were fed B. infantis or placebo for 5 weeks and culled prior to the onset of chronic intestinal inflammation (12–14 weeks). The spleen, Peyers patches and intestinal mucosa were removed and stimulated with various bacterial stimuli. Cytokine levels were measured by enzyme‐linked immunosorbent assay. While basal intestinal and systemic cytokine profiles of WT and IL‐10 KO mice were similar, transforming growth factor (TGF)‐β was reduced in the spleen of IL‐10 KO mice. Following probiotic consumption, interferon (IFN)‐γ was reduced in the Peyers patch of both WT and IL‐10 KO mice. Alterations in IFN‐γ in the Peyers patches of WT mice (enhancement) versus IL‐10 KO (reduction) were observed following in vitro stimulation with salmonella. Differential IL‐12p40, CCL2 and CCL5 responses were also observed in IL‐10 KO mice and WT mice. The cytokine profile of IL‐10 KO mice in early disease was similar to that of WT mice. The most pronounced changes occurred in the Peyers patch of IL‐10 KO mice, suggesting a probiotic mechanism of action independent of IL‐10. This study provides a rationale for the use of B. infantis 35624 for the treatment of gastrointestinal inflammation.

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis.

UNLABELLED Controlling the cell-substrate interactions at the bio-interface is becoming an inherent element in the design of implantable devices. Modulation of cellular adhesion in vitro, through topographical cues, is a well-documented process that offers control over subsequent cellular functions. However, it is still unclear whether surface topography can be translated into a clinically functional response in vivo at the tissue/device interface. Herein, we demonstrated that anisotropic substrates with a groove depth of ∼317nm and ∼1988nm promoted human tenocyte alignment parallel to the underlying topography in vitro. However, the rigid poly(lactic-co-glycolic acid) substrates used in this study upregulated the expression of chondrogenic and osteogenic genes, indicating possible tenocyte trans-differentiation. Of significant importance is that none of the topographies assessed (∼37nm, ∼317nm and ∼1988nm groove depth) induced extracellular matrix orientation parallel to the substrate orientation in a rat patellar tendon model. These data indicate that two-dimensional imprinting technologies are useful tools for in vitro cell phenotype maintenance, rather than for organised neotissue formation in vivo, should multifactorial approaches that consider both surface topography and substrate rigidity be established. STATEMENT OF SIGNIFICANCE Herein, we ventured to assess the influence of parallel groves, ranging from nano- to micro-level, on tenocytes response in vitro and on host response using a tendon and a subcutaneous model. In vitro analysis indicates that anisotropically ordered micro-scale grooves, as opposed to nano-scale grooves, maintain physiological cell morphology. The rather rigid PLGA substrates appeared to induce trans-differentiation towards chondrogenic and/or steogenic lineage, as evidence by TILDA gene analysis. In vivo data in both tendon and subcutaneous models indicate that none of the substrates induced bidirectional host cell and tissue growth. Collective, these observations indicate that two-dimensional imprinting technologies are useful tools for in vitro cell phenotype maintenance, rather than for directional neotissue formation, should multifactorial approaches that consider both surface topography and substrate rigidity be established.

A potentiometric biosensor for rapid on-site disease diagnostics

Quantitative point-of-care (POC) devices are the next generation for serological disease diagnosis. Whilst pathogen serology is typically performed by centralized laboratories using Enzyme-Linked ImmunoSorbent Assay (ELISA), faster on-site diagnosis would infer improved disease management and treatment decisions. Using the model pathogen Bovine Herpes Virus-1 (BHV-1) this study employs an extended-gate field-effect transistor (FET) for direct potentiometric serological diagnosis. BHV-1 is a major viral pathogen of Bovine Respiratory Disease (BRD), the leading cause of economic loss (

The influence of anisotropic nano- to micro-topography on in vitro and in vivo osteogenesis

2 billion annually in the US only) to the cattle and dairy industry. To demonstrate the sensor capabilities as a diagnostic tool, BHV-1 viral protein gE was expressed and immobilized on the sensor surface to serve as a capture antigen for a BHV-1-specific antibody (anti-gE), produced in cattle in response to viral infection. The gE-coated immunosensor was shown to be highly sensitive and selective to anti-gE present in commercially available anti-BHV-1 antiserum and in real serum samples from cattle with results being in excellent agreement with Surface Plasmon Resonance (SPR) and ELISA. The FET sensor is significantly faster than ELISA (<10 min), a crucial factor for successful disease intervention. This sensor technology is versatile, amenable to multiplexing, easily integrated to POC devices, and has the potential to impact a wide range of human and animal diseases.

Electroanalysis at the nanoscale.

AIM Topographically modified substrates are increasingly used in tissue engineering to enhance biomimicry. The overarching hypothesis is that topographical cues will control cellular response at the cell-substrate interface. MATERIALS & METHODS The influence of anisotropically ordered poly(lactic-co-glycolic acid) substrates (constant groove width of ~1860 nm; constant line width of ~2220 nm; variable groove depth of ~35, 306 and 2046 nm) on in vitro and in vivo osteogenesis were assessed. RESULTS & DISCUSSION We demonstrate that substrates with groove depths of approximately 306 and 2046 nm promote osteoblast alignment parallel to underlined topography in vitro. However, none of the topographies assessed promoted directional osteogenesis in vivo. CONCLUSION 2D imprinting technologies are useful tools for in vitro cell phenotype maintenance.

Trace metal determination as it relates to metallosis of orthopaedic implants: Evolution and current status.

This article reviews the state of the art of silicon chip-based nanoelectrochemical devices for sensing applications. We first describe analyte mass transport to nanoscale electrodes and emphasize understanding the importance of mass transport for the design of nanoelectrode arrays. We then describe bottom-up and top-down approaches to nanoelectrode fabrication and integration at silicon substrates. Finally, we explore recent examples of on-chip nanoelectrodes employed as sensors and diagnostics, finishing with a brief look at future applications.

Multi-colour emission from dye doped polymeric nanotubes by host–guest energy transfer

In utilising metal surfaces that are in constant contact with each other, metal-on-metal (MoM) surgical implants present a unique challenge, in the sense that their necessity is accompanied by the potential risk of wear particle generation, metal ion release and subsequent patient toxicity. This is especially true of orthopaedic devices that are faulty and subject to failure, where the metal surfaces undergo atypical degradation and release even more unwanted byproducts, as was highlighted by the recent recall of orthopaedic surgical implants. The aim of this review is to examine the area of metallosis arising from the wear of MoM articulations in orthopaedic devices, including how the surgical procedures and detection methods have advanced to meet growing performance and analytical needs, respectively.

Controlled assembly of Au nanorods into 1D architectures by electric field assisted deposition

Emission chromaticity tuning in polymeric nanotubes was achieved by transfer of excitation energy from a polymer host matrix poly(N-vinylcarbazole) (PVK) to incorporated luminescent chromophore guests (Coumarin 6 and Nile red). Nanotubes were synthesized in densely packed arrays by solution assisted template wetting. Un-doped PVK tubes displayed blue luminescence while Coumarin 6 and Nile red doped tubes exhibited characteristic green and red luminescence with minimal PVK emission, confirming effective host–guest energy transfer. The emission spectral data of single nanotubes, and indicated that, by varying the type and relative concentrations of the dopant dyes, nanotube emission could be tuned from the blue, through green and yellow, to the red and, ultimately, to white, while maintaining excellent color purity.