ReviewFluorescence-based glucose sensors
Section snippets
Introduction: diabetes and glucose sensing
There is now good evidence that the chronic complications of diabetes are related to the duration and severity of hyperglycaemia (Diabetes Control and Complications Trial Research Group, 1993, UK Prospective Diabetes Study Group, 1998). However, good diabetic control is very difficult to achieve in many diabetic patients and frequent blood glucose testing is needed to detect hyper- and hypoglycaemia, and to adjust treatment to correct these deviations and maintain long-term near-normoglycaemia.
Why fluorescence?
The advantages of molecular fluorescence for biosensing include the following:
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The technique is extremely sensitive. There are increasing examples of even single-molecule detection using fluorescence methods (Weiss, 1999).
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Fluorescence measurements cause little or no damage to the host system. In addition, since near-infrared light passes through several centimetres of tissue, with the appropriate choice of fluorophore, molecules can in theory be excited and the emission interrogated from outside
Fluorescence-based glucose sensors
A convenient way of classifying glucose sensors that involve measurements of fluorescence is either according to the type of molecular receptor for glucose, or whether cells or tissues are used to signal glucose concentrations and/or glucose metabolism.
Intrinsic fluorescence of cells
Recently, we have been investigating the notion that the intrinsic fluorescence of tissues such as skin can be used as a reporter of glucose metabolism and thus blood glucose concentrations (Evans et al., 2003). We hypothesized that the fluorescent cofactor NAD(P)H is produced from non-fluorescent NAD in many glucose-dependent metabolic pathways, including the tricarboxylic acid cycle, glycolysis and the hexose monophosphate pathway. NAD(P)H has a fluorescence with a maximum at about 440–480 nm
Conclusions
There are few fluorescence-based glucose detection methods that have reached the stage of testing in vivo, and none have entered clinical practice in diabetes management. This will clearly be an area of active investigation in the coming years—we will need, for example, to explore potential interferents and the stability and accuracy under real-life conditions. Given the problems associated with the presently available in vivo glucose sensors based on implanted amperometric enzyme electrodes
Acknowledgements
We are grateful to the Engineering and Physical Sciences Research Council, the Wellcome Trust and the Diabetes Foundation for financial support.
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