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Biomedical subjects

B J Bellhouse

Publications and source records attributed to B J Bellhouse.

At least 19 recordsLinked to original sources

Identification of second harmonic optical effects from vaccine coated gold microparticles.

This study investigates the optical effects observed from uncoated and protein vaccine coated gold microparticles while imaging with two-photon excitation in the Mie scattering regime. When observed with time correlated single photon counting fluorescence lifetime microscopy, the emission from the gold microparticles appeared as an intense instrument-limited temporal response. The intensity of the emission showed a second-order dependence on the laser power and frequency doubling of the emitted light was observed for fundamental light between 890 and 970 nm. The optical effect was attributed to two-photon induced second harmonic generation. The vaccine coated gold microparticles had a much weaker second harmonic signal than the uncoated gold microparticles. Chemical analysis of the surface of the gold microparticles revealed that the vaccine coating decreases the surface charge thereby diminishing the observed second harmonic signal. These optical properties can be exploited to identify both the location of the protein vaccine coating as well as the gold microparticles in vitro and potentially to investigate the vaccine delivery kinetics in vivo.

Drug Delivery Systems↗

Development of a dye-ligand affinity membrane for the separation of bovine serum albumin.

This study reports the development and testing of a dye-ligand membrane. A synthetic dye called Cibacron Blue F3G-A was utilized as the capturing ligand. Bovine serum albumin acted as the target protein. To immobilize the dye molecules, a microfiltration membrane (Versapor) was used as the supporting matrix. The pore size rating of this membrane was reported to be 0.45 micron. Two different methods of dye immobilization were tested. In the first method, the ligand was directly attached to the membrane, whilst in the second method, a spacer molecule was first coupled to the matrix and then dye coupling was carried out. The chemical stability of the adsorbed dye was studied by subjecting the dye-membranes to appropriate desorption protocols. As a model affinity system, the adsorption of bovine serum albumin onto the dye-membranes was thoroughly investigated. The equilibrium behavior and the kinetic parameters of the BSA-dye interaction were determined experimentally.

Adsorption↗

Transdermal and transmucosal powdered drug delivery.

High-velocity powder injection is a promising new drug-delivery technique that provides needle- and pain-free delivery of traditional drugs, drugs from biotechnology such as proteins, peptides, and oligonucleotides as well as traditional and genetic vaccines. The energy of a transient helium gas jet accelerates fine drug particles of 20 microns-100 microns diameter to high velocities and delivers them into skin or mucosal sites. This review describes the configuration and operating principles of devices that accelerate the particles, the required properties of the particles, the characteristics of the target tissues, and features of the developmental test methods. Preclinical and clinical results that best characterize the technology and introduce its potential as a drug-delivery platform are presented.

Administration, Cutaneous↗

Modelling of the flow-through dye-ligand affinity membrane process using bovine serum albumin as the model protein.

This paper presents the application of a mathematical model for the prediction of the performance of a dye-ligand affinity membrane. Cibacron Blue F3G-A was utilised as the capturing ligand and bovine serum albumin as the target molecule. The dye molecules were immobilised covalently via spacer molecules (polyethlenimine) onto the pores of a microfiltration membrane with a pore size rating of 0.45 micron. Performance analysis of the affinity membranes was achieved by studying the resulting breakthrough curves, when BSA solutions were passed through the system. In the mathematical model, phenomena such as convection, axial dispersion, and adsorption rate of adsorbate were incorporated so that a clearer interpretation of the experimental data could be obtained. Numerical analysis was used to solve the governing partial differential equations.

Chromatography, Affinity↗

Oral PowderJect: a novel system for administering local anaesthetic to the oral mucosa.

OBJECTIVE: To assess the feasibility of using an Oral PowderJect (OPJ) to safely deliver a dose of dry powdered anaesthetic to the oral mucosa, producing an analgesic effect. DESIGN: Single centre: Part 1. An open, non-randomised safety study to check for mucosal damage; Part 2. A double blind sham controlled study to test the anaesthetic effect. SETTING: General practice. SUBJECTS: Adult, healthy volunteers (4 male, 10 female). MATERIALS AND METHODS: Part 1. An OPJ was used to deliver powdered lidocaine hydrochloride to the mucosal surface which was then checked visually for damage. Part 2. An OPJ containing lidocaine hydrochloride (active) or an empty OPJ (sham) was fired at the oral mucosa. The treated area and an untreated (control) site were probed with the back end of a dental needle. RESULTS: The OPJ delivery caused no visible mucosal damage. The median VAS score for pain on blunt probing was 10 for the OPJ active sites. This was significantly lower than the median VAS score for the sham sites at 30 (P = 0.0033) and the control sites at 58 (P < 0.0001). CONCLUSIONS: The OPJ can safely deliver powdered lidocaine hydrochloride to the oral mucosa without causing tissue damage. The OPJ delivery of powdered lidocaine hydrochloride can significantly reduce the pain from a blunt needle probe at 1 minute post delivery.

Adult↗

A novel membrane bioreactor for microbial growth.

A novel membrane bioreactor, previously assessed for its gas transfer characteristics, was used in various size and membrane configurations for the growth of the strictly aerobic bacterium Pseudomonas aeruginosa. The bioreactor was found to readily support growth, and the initial growth rates showed the previously demonstrated enhanced effect in gas O2 mass transfer of the dimpled membrane bioreactor over flat membrane bioreactors. The production of a secondary metabolite by a Pseudomonas sp. following growth was demonstrated, as was the biotransformation of a nitrile by Nocardia rhodochrous with the removal of the biotransformation products across a membrane. The potential of the bioreactor, in terms of other applications in the field of biotechnology, is discussed.

Acrylonitrile↗

Enhanced filtration using flat membranes and standing vortex waves.

The performance of membrane filters is limited by concentration polarisation and membrane fouling. High shear rates reduce these effects but can damage delicate cells and proteins in biological fluids. Secondary flows to promote fluid mixing, and hence enhance filtration, can be highly effective, but usually carry the penalty of complexity. Oscillatory flow over furrowed or dimpled membrane surfaces (vortex mixing) has been shown to be very efficient in the microfiltration and oxygenation of blood, but carries the added complexity of oscillatory flow and the need to thermoform the membranes. To allow the use of asymmetric or rigid membranes, a new form of vortex mixing has been studied, in which the membranes are flat and form parallel channels. Feed flow is oscillatory and passes back-and-forth across ladder-like flow deflectors to generate standing vortex waves. Flow visualisation studies and numerical calculations of standing vortex waves (SVW) were undertaken to help optimise flow parameters and flow deflector geometry. Flat plate membrane ultrafilters were built and evaluated for different geometries of flow deflector, using solutions of bovine serum albumin (BSA) as the test fluid. Very high filtration rates were measured with BSA concentrations ranging from 1 to 24%. A SVW ultrafilter was compared with a Millipore Pellicon ultrafilter using BSA as the test fluid. Filtration flux was similar at low concentrations of BSA, but was greater by a factor of 4.5 in the SVW device at high concentrations of BSA.

Chemical Engineering↗

Quantitative optical determination of the viability of platelet concentrates.

An optical method to assess platelet viability in platelet transfusion concentrates has been developed which is based on the observation that healthy, discoid platelets transmit more light in shear flow than aged, spherical cells. Using a specially designed glass channel, the rise in transmission of light through platelet samples with agitation is referenced against a measurement of transmission without flow. Referencing the measurements may minimize the effects of red blood cell contamination, as well as other variations among platelet packs such as plasma characteristics and plastic container variability. At an optimal frequency of agitation, the ratio of the transmission of light with agitation to that of the sample at rest is found to correlate highly with the concentration of discoid platelets, r = 0.92 to 0.95 (P less than 0.001), for light sources including a HeNe laser and two LEDs. Using this index, the discoid platelet counts of twelve platelet packs are estimated and compared with manual counts. The mean difference between the two methods was 0.009 x 10(9) discoid platelets ml-1 with a standard deviation of 0.11 x 10(9) cells ml-1. We conclude that the method may be applied to the development of a non-invasive device to monitor the concentration of viable, discoid platelets in storage.

Blood Platelets↗

Comparative study of reaction kinetics in membrane and agarose bead affinity systems.

Compared to conventional agarose bead affinity supports, a microporous nylon membrane exhibits greatly improved reaction kinetics as quantified in the reaction between gamma-globulin and immobilised protein A. The improvement is only observed when the solution of gamma-globulin is forced through the membrane pores. In the absence of flow in the pores, it is possible to relate approximately the rate of uptake onto either type of affinity support to independently determined diffusion coefficients. In the presence of flow, the reaction rate is similar for membranes having 0.45 and 3.0 microns diameter pores, and considerably smaller than predicted by the Smoluchowski formula.

Chromatography, Affinity↗

Extracorporeal oxygen and CO2 transfer of a polypropylene dimpled membrane lung with variable secondary flows: partial bypass in the dog.

In vivo gas transfer performance, during veno-venous bypass, is presented for one form of the Oxford membrane lung in which vortex mixing is induced in blood flow across a dimpled polypropylene membrane. Good agreement has been found with in vitro data presented in an earlier paper. Two experiments were extended to attain total extracorporeal CO2 removal with apnoeic diffusion oxygenation to motionless lungs. Measurements of arterial oxygen partial pressure during apnoea suggest that the time-constant for equilibration of alveolar nitrogen partial pressure with that on the gas side of the membrane lung is of the order of 100 min.

Animals↗

Oxygen and CO2 transfer of a polypropylene dimpled membrane lung with variable secondary flows.

Gas transfer performance is presented for one form of the Oxford membrane lung in which vortex mixing is induced in blood flow across a dimpled polypropylene membrane. Dimensional analysis has been used to define the parameters characterizing mass transfer in the device, and of three fluid mechanical parameters: Reynolds number based on peak pulsation velocity, Strouhal number, and ratio of mean to oscillatory flows, only the first has been found to affect mass transfer significantly in the ranges studied. For oxygenation, rated flows in excess of 5 l min-1 m-2 are measured. A new definition is presented for a rated flow for extracorporeal CO2 removal and values in excess of 1.2 l min-1 m-2 are obtained.

Animals↗

Initial in vitro evaluation of a pediatric vortex-mixing membrane lung.

A new design for a pediatric membrane lung is described in this paper. The lung consists of eight blood compartments, each having six U-shaped blood channels, with microporous PTFE membranes supported on rigid plates in such a way that the membranes form furrowed blood channels. Two rolling diaphragm pumps are attached to the open ends of the U-shaped blood channels; these pumps are operated in antiphase. Mean flow is provided by a roller pump placed at the inlet end of the membrane lung. Pulsatile blood flow within the blood channels produces successive vortex formation and ejection, leading to good blood mixing and high efficiency in gas transport. The design of the rolling diaphragm piston pumps ensures that the blood prime volume is low (280 ml), and the grouping of the pumps at one end of the oxygenator allows the driving mechanism to be simple and compact. The relatively wide blood channels (minimum width 0.5 mm) and vortex mixing make priming the membrane lung particularly easy. The membrane area is 0.39 m2. Preliminary performance testing of the pediatric membrane lung was undertaken by pumping blood around a circuit containing a roller pump, the membrane lung, and a bubble oxygenator (to adjust the blood gases at the inlet to the membrane lung). In five such experiments it was shown that the membrane lung transferred 80 ml O2/min and 120 ml CO2/min at a blood flow rate of 1.5 L/min.

Adult↗

Gel layer limited haemofiltration rates can be increased by vortex mixing.

Haemofiltration has been used since 1976 as an alternative to haemodialysis in the treatment of chronic renal failure (1). Ultrafiltration flow rates (UFR) from blood are slow and it has been observed that when blood or plasma is ultrafiltered using highly permeable membranes, the UFR reaches a maximum which is independent of trans-membrane pressure (delta Pm) (2). We have confirmed this result during steady flow through an ultrafilter employing polyacrylonitrile membrane (Rhône Poulenc AN 69) but have also shown that this maximum can be exceeded by a factor of eight in the same device when vortex mixing is induced by pulsing the blood flow over furrowed channels.

Blood↗