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Biomedical subjects

I J Higgins

Publications and source records attributed to I J Higgins.

At least 19 recordsLinked to original sources

Concerning the toxicity of two compounds used as mediators in biosensor devices: 7,7,8,8-tetracyanoquinodimethane (TCNQ) and tetrathiafulvalene (TTF).

The lethal dose (LD50) and the maximum tolerated dose (MTD) of TCNQ and TTF were determined experimentally by single-dose administration to CBA-line mice. The effect of the compounds on the blood constitution, accumulation, acute and subacute dermal and eye irritation, skin sensitization and delayed type hypersensitivity reaction were also monitored in mice and guinea pigs. The LD50s were found to be 1225 mg kg-1 (6.0 mmol kg-1) for TCNQ and 710 mg kg-1 (3.5 mmol kg-1) for TTF; MTDs were 750 mg kg-1 (3.7 mmol kg-1) and 450 mg kg-1 (2.2 mmol kg-1), respectively. Mice that had received the MTD showed no significant change in their measured blood parameters after five days for TTF; however, for TCNQ a decrease in the absolute leucocyte number and changes in the leucoformula were apparent by the fifth day. Oral administration to mice for 28 days at a concentration of 10% of the LD50 showed a super-accumulation, and the accumulation index was 0.94 and 0.53 for TCNQ and TTF, respectively. Neither compound caused acute or subacute dermal irritation of guinea pigs and there was no acute eye irritation. Skin sensitization in guinea pigs and delayed-type hypersensitivity reaction in mice indicated that TCNQ and TTF used as ethanol solutions were not allergic. This study indicates that TCNQ and TTF may be regarded as low-toxicity compounds.

Acute Disease

Biosensors for process control.

Biosensors have been extensively studied during the last 20 years, and a myriad of laboratory biosensors have been developed. Improvements are required in biosensor design and performance before they become widely accepted in industrial process monitoring. However, as the biotechnology industry expands, biosensors may become more acceptable because, despite their limitations, they are the only devices capable of delivering the information required.

Biosensing Techniques

Introduction to the principles and applications of biosensors.

A biosensor is an analytical device that responds to an analyte in an appropriate sample and interprets its concentration as an electrical signal via a suitable combination of a biological recognition system and an electrochemical transducer. As a result of recent scientific and technological progress, such devices are likely to play an increasingly important role in generating analytical information in all sectors of human endeavour, from medicine to the military. In particular, biosensors will form the basis of cheap, simple devices for acquiring chemical information, bringing sophisticated analytical capabilities to the non-specialist and general public alike. The market opportunities for the rapid exploitation of novel developments in this sector are substantial. Biosensor research is also likely to have a significant impact on the development of modern electronics.

Biotechnology

Quinoprotein glucose dehydrogenase and its application in an amperometric glucose sensor.

Glucose dehydrogenase (GDH), one of the recently discovered NAD(P)+-independent 'quinoprotein' class of oxidoreductase enzymes, was purified from Acinetobacter calcoaceticus LMD 79.41 and immobilised on a 1,1'-dimethylferrocene-modified graphite foil electrode. The second-order rate constant (ks) for the transfer of electrons between GDH and ferrocenemonocarboxylic acid (FMCA) in a homogeneous system, determined using direct current (DC) cyclic voltammetry, was found to be 9.4 x 10(6) litres mol-1 s-1. This value of ks for GDH was more than 40 times greater than that for the flavoprotein glucose oxidase (GOD) under identical conditions. Such high catalytic activities were also observed when GDH was immobilised in the presence of an insoluble ferrocene derivative; a biosensor based on GDH was found to produce more than twice the current density of similar GOD-based electrodes. The steady-state current produced by the GDH-based electrode was limited by the enzymic reaction since methods which increased the enzyme loadings elevated the upper limit of glucose detection from 5 mM to 15 mM. The temperature, pH, stability and response characteristics of the GDH-based glucose sensor illustrate its potential usefulness for a variety of practical applications. In particular, the high catalytic activity and oxygen insensitivity of this biosensor make it suitable for in vivo blood glucose monitoring in the management of diabetes.

Acinetobacter

The degradation of 1-phenylalkanes by an oil-degrading strain of Acinetobacter lwoffi.

An oil-degrading bacterium identified as Acinetobacter lwoffi was isolated by elective culture on North Sea Forties crude oil from an activated sludge sample. It grew on a wide range of n-alkanes (C12-C28) and 1-phenylalkanes, including 1-phenyldodecane, 1-phenyltridecane and 1-phenyltetradecane. The organism degraded 1-phenyldodecane to phenylacetic acid which was further metabolized via homogentisic acid, whilst 1-phenyltridecane was transformed to trans-cinamic and 3-phenylpropionic acid which were not further metabolized. Evidence is presented for a relationship between aromatic amino acid catabolism and 1-phenyldodecane degradation in this organism.

Acinetobacter

New findings in methane-utilizing bacteria highlight their importance in the biosphere and their commercial potential.

Recent results, showing that the ubiquitous methane-utilizing bacteria (methanotrophs) can partially oxidize and, in some cases, extensively metabolize complex organic compounds, call for a reappraisal of their role in the cycling of elements in the biosphere. Possible environmental implications and opportunities for industrial exploitation are discussed.

Biological Evolution

Electrochemical, photoelectrochemical, electrocatalytic and catalytic reduction of redox proteins.

Redox proteins catalyse the reactions of a wide variety of otherwise intractable substrates, such as dinitrogen, alkanes, arenes, terpenes and steroids. Two major factors impede the utilization of these enzymes--the inefficient electron transfer between the enzyme and electrode, and the properties often, but not inevitably, associated with enzymes, such as instability, complexity, and expense. We have now shown that the former can be overcome and that proteins can be coupled, via electrodes, to a number of energy sources; the latter is the subject of much effort elsewhere. We demonstrated previously that certain redox proteins can be reduced very efficiently electrochemically (Fig. 1a). Light and hydrogen are the two other convenient energy sources that could be used for such reductions, and we now report the reduction of cytochrome c by these means.

Catalysis