In recent years, with the rise of global diabetes, a growing number of subjects are suffering from pain and infections caused by the invasive nature of mainstream commercial glucose meters. Non-invasive blood glucose monitoring technology has become an international research topic and a new method which could bring relief to a vast number of patients. This paper reviews the research progress and major challenges of non-invasive blood glucose detection technology in recent years, and divides it into three categories: optics, microwave and electrochemistry, based on the detection principle. The technology covers medical, materials, optics, electromagnetic wave, chemistry, biology, computational science and other related fields. The advantages and limitations of non-invasive and invasive technologies as well as electrochemistry and optics in non-invasives are compared horizontally in this paper. In addition, the current research achievements and limitations of non-invasive electrochemical glucose sensing systems in continuous monitoring, point-of-care and clinical settings are highlighted, so as to discuss the development tendency in future research. With the rapid development of wearable technology and transdermal biosensors, non-invasive blood glucose monitoring will become more efficient, affordable, robust, and more competitive on the market.

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Skin penetration is related to efficiencies of drug delivery or ISF extraction. Normally, the macro-electrode is employed in skin permeability promotion and evaluation, which has the disadvantages of easily causing skin damage when using electroporation or reverse iontophoresis by alone; furthermore, it has large measurement error, low sensitivity, and difficulty in integration. To resolve these issues, this paper presents a flexible interdigital microelectrode for evaluating skin penetration by sensing impedance and a method of synergistical combination of electroporation and reverse iontophoresis to promote skin penetration. First, a flexible interdigital microelectrode was designed with a minimal configuration circuit of electroporation and reverse iontophoresis for future wearable application. Due to the variation of the skin impedance correlated with many factors, relative changes of it were recorded at the end of supply, different voltage, or constant current, times, and duration. It is found that the better results can be obtained by using electroporation for 5 min then reverse iontophoresis for 12 min. By synergistically using electroporation and reverse iontophoresis, the penetration of skin is promoted. The results tested in vivo suggest that the developed microelectrode can be applied to evaluate and promote the skin penetration and the designed method promises to leave the skin without damage. The electrode and the method may be beneficial for designing noninvasive glucose sensors.

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