ReviewCurrent development in non-invasive glucose monitoring
Introduction
Glucose is the main carrier of energy in the human organism, with recommended levels between 4.9 mmol/L and 6.9 mmol/L in whole or capillary blood [1]. The sugar concentration in blood is controlled by the islet cells in the pancreas through the production of the glucagon hormone This hormone raises the level of blood sugar, and insulin, responsible for helping the body to change glucose into energy [2]. World wide, 150 million people suffer from disturbances in the endocrine metabolic regulation, called diabetes. Approximately 10% of cases result from insulin deficiency (type 1), which often starts during childhood and requires giving this hormone usually many times a day. Insulin resistance (type 2) corresponds to 90%, occurring more in people over 40 years old. Additional cases also are related to pregnancy, where 2% of women have gestational diabetes [3]. Any kind of diabetes can be dangerous because long-term excess of glucose (hyperglycemia) can cause blindness, damaged nerves and kidneys (renal failure), or even increase the risk of heart diseases, strokes, and birth defects. Low levels (hypoglycemia), however, can result in confusion, coma and even death [4].
Fig. 1 shows different classifications of blood glucose monitoring: invasive, minimally invasive and non-invasive. Fully invasive systems can be either bedside clinical devices or self-monitoring meters. Bedside monitors are suitable for intensive care units and use sensors with an accuracy of approximately 1% [5]. Such systems allow continuous monitoring, therefore increasing the amount of clinical information.
Systems which puncture the skin are still standard techniques for home monitoring (6–7% accuracy) reading glucose concentrations through electrochemical, colorimetric or optical disposable strips for finger-prick blood samples [6]. Efforts have been made in order to reduce the level of invasiveness by decreasing the blood sample volume to a few microlitres, and measuring areas of the body less sensitive to pain than fingertips, such as the forearm, upper arm, or thigh. Drawbacks of such systems area lack of control during sleeping or manual activities, undiscovered episodes of hyper- or hypoglycaemia, risks of infection, nerve damage and the discomfort of pricking the finger several times a day, which painful activity often leads to non-compliance [7].
Minimally invasive measurements sample the interstitial fluid (ISF) with subcutaneous sensors [8]. Even in this method the discomfort causes difficulties to the patient's therapy. Therefore, research groups are working to develop non-invasive glucose control devices [9]. Unfortunately, so far there are no reports or patents which show that such non-invasive methods have the same accuracy as invasive procedures.
Although there are many complete reviews of painless blood glucose techniques [10], [11], [12], the great volume of recent research results in this field requires a constant update. Therefore, besides the description of important measurement approaches, this work also shows available devices on the market with their technologies and measurement sites. Because absorption spectroscopy is a widely sensing method, the wavelengths used in non-invasive tests will also be described. In addition, algorithms for multivariate analysis will be presented, showing that recent improvements in technologies and multiparameter measurements may still enable improved accuracy of the predictions.
Section snippets
Non-invasive glucose monitoring
One option to painless intermittent glucose control is the substitution of blood with other fluids that could contain glucose, like saliva, urine, sweat or tears [13], [14]. But continuous monitoring could only be accomplished through direct measurement of body tissues such as skin, cornea, oral mucosa, tongue or tympanic membrane [15], [16]. Non-invasive glucose transducers should be capable of detecting weak blood signals through intervening tissues (bone, fat, skin, etc.), and in addition,
Conclusions
An increase of the signal-to-noise ratio (SNR) is still required for all non-invasive assays. This should be accomplished with a new generation of transducers and methods. The parallel monitoring of more than one parameter should also help to improve sensitivity. Initial studies have already been reported with simultaneous monitoring of bioimpedance and near-infrared spectroscopy in the skin [68]. The Glucotrack device from the company Integrity Applications is a commercial multiparameter
Conflict of interest
No financial and personal relationships with other people or organisations that could inappropriately influence (bias) my work.
Acknowledgments
This work was supported by the German Academic Exchange Service (DAAD) and Heinz Nixdorf Stiftung.
Carlos Edurado Ferrante do Amaral received the B.A.Sc. and M.A.Sc. degrees in electrical and biomedical engineering from the Paraná Federal Center of Technological Education (CEFET/PR), Curitiba, Brazil, in 2001 and 2004, respectively. He is currently pursuing the Ph.D. degree in biomedical engineering at the Heinz Nixdorf-Chair for Medical Electronics, Technical University of Munich, Germany, under the supervision of Prof. B. Wolf. His research interests include non-invasive monitoring
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Carlos Edurado Ferrante do Amaral received the B.A.Sc. and M.A.Sc. degrees in electrical and biomedical engineering from the Paraná Federal Center of Technological Education (CEFET/PR), Curitiba, Brazil, in 2001 and 2004, respectively. He is currently pursuing the Ph.D. degree in biomedical engineering at the Heinz Nixdorf-Chair for Medical Electronics, Technical University of Munich, Germany, under the supervision of Prof. B. Wolf. His research interests include non-invasive monitoring techniques, rehabilitation, analytical chip technology, blood analysis methods, bioimpedance and light spectroscopy.
Bernhard Wolf received the B.Sc., M.Sc. and Ph.D. degrees in biology from Albert–Ludwigs-Universität, Freiburg, Germany. He is Professor and Head of the Heinz Nixdorf-Chair for Medical Electronics, Technical University of Munich, Munich, Germany. His primary research interests lie in the areas of cell based assays, analytical electron microscopy, bioelectronics and medical electronics, bioelectronic home care systems, biohybrid devices, biosensors, tumor diagnostics and therapy, structured biological modelling, micro-bioreactors and magneto stimulation. He is one director of the Central Institute of Medical Technology (IME-TUM) and is a member of European Microanalytical Society (EMAS). D. Wolf has published widely in these areas and holds several patents in cell chip monitoring. He serves on the Editorial Board of the German Journal of Oncology, and Biomedical Engineering of the TÜV Süddeutschland.