Electroactive biomolecular wires for rapid and online non-invasive detection of diabetic and pre-diabetic conditions

Diabetes mellitus is on the increase in the UK, with contributory factors including obsesity, lack of exercise, poor diet and genetic predispositions. The main costs associated with its treatment is approximately £3.5 billion (ca. 5% of the total NHS budget). The clincial chemical hallmark of the disease is elevated blood glucose levels (hyperglycaemia) and urinary glucose excretion. However, glucose is only excreted by the kidney above the ca. 10 mM concentration level, and it follows that saliva glucose concentrations may be a more appropriate 'early-warning' marker for the disease. Associated with the diabetic condition are elevated concentrations of F2-isoprostanes in blood plasma and urine (due to the greater degree of general oxidative stress within the patient body system), augmented levels of 8-hydroxydeoxyguanosine in urine, and subnormal concentrations of vitamin C. Furthermore, the presence of advanced glycosylation end products within urine may reflect the actual 'biological age' of the sufferer. This multi-partied research across clinical, organic and physico-analytical chemistries proposes the development of a hand-held, portable device for a non-invasive urineand saliva test which may be used as a rapid 'health screen' examination for patients with both diabetes mellitus and a pre-diabetic condition (imparied fasting glucose or imparied glucose tolerence) and diabetes using measurements at microelectrodes. The latter are known to exhibit superior signal-to-noise ratios than millimetric electrodes. The innovation involves employing natural biochemical receptors (such as proteins, for example enzymes or anitbodies, or DNA bases) to target the analyte, whilst monitoring the presence of the interaction between target and receptor using the reversible electrolysis of a chemical functionality (such as a 1,4-benzenediamine) attached to the bio-receptor, and which additionally connects ('wires') both biological and electrochemical moieties to an electrode surface. The advantages of this combinatorial methodology is that there is no single target, rather it is a monitoring of the principle biomarker (glucose) together with the simultaneous measurment of the associated biochemicals (F2-isoprostanes, 8-hydroxydeoxyguanosie, ascorbic acid, glycosylation end-products). Moreover, there is no need for sample preparation prior to measurement using this combinatorial device: urine and saliva samples typically contain electrolytes, the amount of which can be readily assesed from the reversible electrolysis of an additional control compound sensitive to salt concentrations (such as a tetra-substituted-para-pheneylenediamine). This means that the sensing reveals a substantial degree of clincial chemical parameters, sensitive to the associated medical condition. It follows that the reliable measurement followed by analysis of clinical samples may lead to the early diagnosis of this medical problem, and to the envisaged development of a point-of-care detection device. Moreover, the deduction of a true 'bio-age' of a patient series enables the development of predicted values, so that patients can be empowered to look after their own health. Accordingly, this work is supported by a multi-disciplinary team comprising physico-analytical electrochemist (Dr. J. D. Wadhawan), synthetic bio-organic chemist (Dr. G. Mackenzie), clinical diabetes consultant (Professor S. L. Atkin) and Boots, PLC (Mr. E. Galley). The university team is uniquely suited to the company requirement. The collaborative benefits for both university and company are large, and include the undertaking and good publicity for the university as a result of high quality and successful research, coupled with its commercialisation.