Optical microchip array biosensor for multiplexed detection of bio-hazardous agents.

An optical waveguide array biosensor suitable for rapid detection of multiple bio-hazardous agents is presented. SpectroSens™ optical microchip sensors contain multiple spatially-separated waveguide channels with integral high-precision Bragg gratings sensitive to changes in refractive-index; selective surface-functionalisation of discrete sensing channels with different antibodies as bio-recognition elements enables selective multi-analyte biological detection. Interactions between target antigens in the test sample and respective surface-immobilised antibodies result in localised changes in refractive-index; the biosensor response manifests as increases in wavelength of light reflected from specific sensing channels. Multiplexed, label-free detection of 8 different biological agents, encompassing bacterial spores, vegetative cells, viruses and proteinaceous toxins has been demonstrated in real-time. Selective detection of Bacillus atrophaeus (BG) spores, Escherichia coli cells, MS2 viruses and ovalbumin (OVA) protein (simulant bio-hazardous agents) was first demonstrated as proof-of-concept; subsequently, detection of Bacillus anthracis (BA) spores (UM23CL2 strain), Franciscella tularensis (FT) cells (live vaccine strain), Vaccinia viruses (heat-killed) and ricin toxin (bio-hazardous agents) was proven. Two optical microchip sensors, each comprising 8 sensing channels were packaged into a single disposable cartridge allowing simultaneous 16-channel data acquisition. The specific antibody deposition sequence used in this study enabled detection of either 4 simulants or 4 bio-hazardous agents using a single consumable. The final device, a culmination of the multidisciplinary convergence of the fields of biology, chemistry, optoelectronics and microfluidics, is man-portable and inherently robust. The performance characteristics of the SpectroSens™ technology platform highlight its potential for exploitation as a 'detect to warn/treat' biodetector in security and defence operations.

Performance of a quarter-wavelength particle concentrator.

A series of devices have been investigated which use acoustic radiation forces to concentrate micron sized particles. These multi-layered resonators use a quarter-wavelength resonance in order to position an acoustic pressure node close to the top surface of a fluid layer such that particles migrate towards this surface. As flow-through devices, it is then possible to collect a concentrate of particulates by drawing off the particle stream and separating it from the clarified fluid and so can operate continuously as opposed to batch processes such as centrifugation. The methods of construction are described which include a micro-fabricated, wet-etched device and a modular device fabricated using a micro-mill. These use silicon and macor, a machinable glass ceramic, as a carrier layer between the transducer and fluid channel, respectively. Simulations using an acoustic impedance transfer model are used to determine the influence of various design parameters on the acoustic energy density within the fluid layer and the nodal position. Concentration tests have shown up to 4.4-, 6.0- and 3.2-fold increases in concentration for 9, 3 and 1 microm diameter polystyrene particles, respectively. The effect of voltage and fluid flow rates on concentration performance is investigated and helps demonstrate the various factors which determine the increase in concentration possible.

Development of a novel compact sonicator for cell disruption.

Ultrasound microbial cell disrupters operating at around 20 kHz are often physically large and, due to significant heating, can be unsuitable for small sample volumes where biochemical integrity of the extracted product is required. Development of a compact device based on a 63.5-mm diameter, 6.5-mm thick tubular transducer for rapid cell disruption in small-volume samples in a high-intensity acoustic cavitation field with minimal temperature rises is described here. Suspensions of Saccharomyces cerevisiae were exposed to cavitation for various times in the compact device and a 20-kHz probe sonicator. Cell disruption was assessed by protein release and by staining. Yeast cell disruption was greater in the novel 267-kHz sonicator than in the 20-kHz probe sonicator for the same exposure time. A 1-dimensional (1-D) transfer matrix model analysis for piezoelectric resonators was applied to an axial cross-section of the tubular sonicator to predict frequencies of mechanical resonance in the sample volume associated with maximum acoustic pressure. Admittance measurements identified frequencies of electrical resonance. Ultrasonic cavitation noise peaks were detected by a hydrophone at both the mechanical and electrical resonances. Cell breakage efficiency was twice as great in terms of protein released per dissipated watt at the mechanical resonance predicted by the model, compared to those at the electrical resonance frequencies. The results form a basis for rational design of an ultrasound cell disruption technique for small-volume samples.

The association between depressive symptoms and health status in patients with chronic pulmonary disease.

This study evaluated the association between depressive symptoms and health related quality of life (HRQoL) in patients with chronic pulmonary disease using both general and disease-specific HRQoL measures. A cross-sectional analysis of HRQoL measures completed by patients enrolled in the Department of Veteran Affairs Ambulatory Care Quality Improvement Project. 1252 patients with chronic pulmonary disease screened positive for emotional distress and returned the Hopkins Symptom Checklist-20 (SCL-20). 733 of 1252 had a score of 1.75 or greater on the SCL-20 indicating significant depressive symptoms. Depressive symptoms were associated with statistically significantly worse general and pulmonary health as reflected by lower scores on all sub-scales of both the Medical Outcomes Short Form-36 and the Seattle Obstructive Lung Disease Questionnaire. In fact, 11% to 18% of the variance in physical function sub-scales was attributed to depressive symptoms alone. Patients with chronic pulmonary disease and depressive symptoms reported significantly more impaired functioning and worse health status when compared to those patients without depressive symptoms. Because there are highly effective treatments for depression, selective screening of patients with chronic pulmonary disease for depression may identify a group that could potentially benefit from treatment interventions.

pH dependence of hydrochloric acid diffusion through gastric mucus: correlation with diffusion through a water layer using a membrane-mounted glass pH electrode.

Solute diffusion coefficients (D) can indicate a dependence upon actual solute concentrations. Here a single compartment has been utilized, in which effective HCl diffusion to a membrane-mounted glass pH electrode can be measured across the pH spectrum. The study has investigated HCl diffusion through both mucus and water layers as a function of HCl concentration. The observed dynamic responses of a liquid-film and mucus-coated electrodes over a range of HCl concentrations suggest that the speed at which equilibrium is attained is pH dependent; equilibrium was reached rapidly under more acidic and alkaline conditions. Estimated values of DHCl also indicate a strong pH dependence for both liquid film and mucus. In both instances, a greater than 10-fold reduction in DHCl at pH 7.5 as compared with that at pH 3.5 has been demonstrated. Furthermore, estimated values of DHCl are approximately 4-fold smaller through the mucus gel, as compared with a water layer. The findings indicate that the most powerful influence on diffusional resistance is pH itself, whereby a marked drop in H+ diffusion is likely to occur towards neutral pH irrespective of the composition of the gel barrier. Possible implications of the findings are discussed in relation to mucosal protection from acid.