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Biomedical subjects

Stephen J Haswell

Publications and source records attributed to Stephen J Haswell.

18 recordsLinked to original sources
PubMed2006

Scaling out of electrolyte free electrosynthesis in a micro-gap flow cell.

The electro-reductive coupling of activated olefins and benzyl bromide derivatives has been selected to compare the performance of single and multiple channel (scaled-out) micro-gap electrochemical flow reactors. Two working electrode configurations were evaluated; in the first a single set of electrodes was used in conjunction with a multiple flow manifold to give two and four separate flow channels; in the second independent electrodes were used within the same flow manifold. Problems with shunt currents and Joule heating in the first configuration meant that only the second configuration was reliable, giving results comparable to those obtained for the single flow cell. Excellent yields of the coupling products such as 2-benzyl-succinic acid dimethyl ester and derivatives were obtained. This demonstrates micro reactor scale-out for unsupported electrosyntheses.

Journal Article↗
PubMed2006

Continuous flow separation of particles within an asymmetric microfluidic device.

A microfluidic based device has been developed for the continuous separation of polymer microspheres, taking advantage of the flow characteristics of systems. The chip consists of an asymmetric cavity with variable channel width which enables continuous amplification of the particle separation for different size particles within the laminar flow profile. The process has been examined by varying the sample inlet position, the sample to media flow rate ratio, and the total flow rate. This technique can be applied for manipulating both microscale biological and colloidal particles within microfluidic systems.

Colloids↗
PubMed2006

A microfluidic-based system for analysis of single cells based on Ca2+ flux.

A microfluidic format-based system has been developed for in situ monitoring of the calcium flux response to agonists using Chinese hamster ovary (CHO) cells. The assay is based on measuring the fluorescent intensity of the calcium-sensitive indicator, Fluo-4 AM, and was performed in a modified glass chip channel, whose surface was functionalised using a silanisation method with 3-aminopropyltriethoxysilane (APTS) (enabling the cells to be immobilised on the channel surface). CHO cells calcium flux response was measured for different agonists over a range of concentrations. Cells and reagents were introduced into the chip in a continuous flow as a series of plugs in a given sequence.

Aniline Compounds↗
PubMed2005

The application of micro reactors for organic synthesis.

This tutorial review describes how micro reactors are being applied to synthetic chemistry covering a wide range of applications, from the preparation of nanograms of material for drug discovery and screening to the multi-tonne production of fine chemicals. This article explores how miniaturisation may revolutionise chemical synthesis and demonstrates that products are generated in higher yield and purity compared to the equivalent bulk reactions, in much shorter periods of time.

Combinatorial Chemistry Techniques↗
PubMed2004

Organic synthesis in micro reactors.

This article reviews the current and future applications of micro reactors in the field of chemistry, biochemistry and drug discovery. The fabrication and physical characterisation of micro reactors, together with details of their use and operation is described. Liquid and gas phase reactions have been used to illustrate the advantages of performing chemical reactions in micro reactors. A brief evaluation of the possible advantages that micro fabrication could offer in developing biological applications, based on miniaturized devices is also presented.

Biosensing Techniques↗
PubMed2003

Microwave heating of heterogeneously catalysed Suzuki reactions in a micro reactor.

The Suzuki cross-coupling reaction of aryl halides with phenylboronic acid to form biaryls has been used to illustrate the development of a microwave based technique capable of delivering heat locally to a heterogeneous Pd-supported catalyst located within a micro reactor device. A 10-15 nm gold film patch, located on the outside surface of the base of a glass micro reactor, was found to efficiently assist in the heating of the catalyst when irradiated with 5-7 W of microwave power at 2.45 GHz. Using a hydrodynamically pumped system, reactant-catalyst contact times of less than 60 s were found to give conversions for different substrates which were in the range 50-99%. Two methods of loading catalysts into the micro reactor were investigated which required either 1.5 or 6 mg of material.

Journal Article↗
PubMed2003

Continuous flow reactors for drug discovery.

To develop a new generation of drugs, pharmaceutical companies need to be able to synthesize and screen novel chemicals with enhanced speed. New technology that would enable a cost-neutral increase in the number of potential drug candidates would provide a distinct competitive advantage. The miniaturisation of chemical reactors offers many fundamental and practical advantages of relevance to the pharmaceutical industry, which is constantly searching for controllable, information-rich, high-throughput and environmentally friendly methods of producing compounds with a high degree of chemical selectivity. This article reviews the current and future applications of micro reactors that could enhance the drug discovery process.

Chemistry, Pharmaceutical↗
PubMed2003

Monitoring of chemical reactions within microreactors using an inverted Raman microscopic spectrometer.

An inverted Raman microscope spectrometer has been used to profile the spatial evolution of reactant and product concentrations for a chemical reaction within a microreactor operating under hydrodynamic flow control. The Raman spectrometer was equipped with a laser source at wavelength of 780 nm, confocal optics, a holographic transmission grating, and a charge-coupled device (CCD) detector. The microreactor consisted of a T-shaped channel network etched within a 0.5 mm thick glass bottom plate that was thermally bonded to a 0.5 mm thick glass top plate. The ends of the channel network were connected to reagent reservoirs that were linked to a syringe pump for driving the solutions by hydrodynamic pumping within the channels. The microchannels were 221 micro m wide and 73 micro m deep. The synthesis of ethyl acetate from ethanol and acetic acid was investigated as a model system within the microreactor as Raman scattering bands for each reactant and product species were clearly resolved. Raman spectral intensities of each band were proportional to concentration for each species and hence all concentrations could be quantitatively measured after calibration. By scanning specific Raman bands within a selected area in the microchannel network at given steps in the X-Y plane, spatially resolved concentration profiles were obtained under steady-state flow conditions. Under the flow conditions used, different positions within the concentration profile correspond to different times after contact and mixing of the reagents, thereby enabling one to observe the time dependence of the product formation. Raman microscopy provides a useful complementary technique to UV/VIS absorbance and fluorescence methods for the in situ monitoring and analysis of chemical reaction species having their lowest S(0)-S(1) absorption bands too far in the UV to be of use, due to their probable overlap with the bands from other reactant, product and solvent molecules.

Acetates↗
PubMed2003

Microfluidic combinatorial chemistry.

Microreactors are finding increasing application in the field of combinatorial chemistry. In the past few years, microreactor chemistry has shown great promise as a novel method on which to build new chemical technology and processes. It has been conclusively demonstrated that reactions performed within microreactors invariably generate relatively pure products in high yield. One of the immediate and obvious applications is therefore in combinatorial chemistry and drug discovery.

Combinatorial Chemistry Techniques↗
PubMed2002

Investigation of racemisation in peptide synthesis within a micro reactor.

We demonstrate that peptides derived from alpha-amino acids may be prepared in a micro reactor. The peptides were prepared in 20 min with quantitative conversion, compared to batch reactions which require prolonged reaction times. We illustrate that by using dilute reagent concentrations and short reaction times, less racemisation is observed in micro reactions than in bulk reactions.

Indicators and Reagents↗
PubMed2002

Electrokinetic control of a chemical reaction in a lab-on-a-chip micro-reactor: measurement and quantitative modelling.

We have investigated the complex formation/dissociation reaction between Ni(2+) ions and the ligand pyridine-2-azo-p-dimethylaniline (PADA) in a glass micro-reactor operating under electrokinetic control. An in situ, microscope-imaging technique was used to determine the spatial and temporal evolution of the reaction within the channel network of the micro-reactor. Using appropriately controlled voltage sequences, a 'slug' of PADA was injected into a stream of Ni(2+) solution. Under the experimental reaction conditions used, Ni(2+) ions are mixed with the PADA as a consequence of the species' different electrokinetic mobilities allowing the complex formation to occur at the trailing edge of the PADA slug. Following complex formation, reversal of the flow results in the partial re-formation of free PADA by dissociation of the complex, demonstrating that voltage control can be used to drive the reaction either forwards or backwards. We discuss the methods whereby all the parameters required to predict the spatial and temporal evolution of the reaction in the micro-reactor can be either measured or estimated. Based on the estimated parameters, model calculations of the concentration profiles as a function of time show good agreement with the measured data.

Journal Article↗
PubMed2002

Metal imbalance and compromised antioxidant function are early changes in prion disease.

The prion protein (PrP) has been shown to bind copper. In the present study we have investigated whether prion disease in a mouse scrapie model resulted in modification of metal concentrations. We found changes in the levels of copper and manganese in the brains of scrapie-infected mice prior to the onset of clinical symptoms. Interestingly, we noted a major increase in blood manganese in the early stages of disease. Analysis of purified PrP from the brains of scrapie-infected mice also showed a reduction in copper binding to the protein and a proportional decrease in antioxidant activity between 30 and 60 days post-inoculation. We postulate that alterations in trace-element metabolism as a result of changes in metal binding to PrP are central to the pathological modifications in prion disease.

Animals↗