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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This study focuses on preparation and valuation of the biodegradable, native, and modified gelatin film as screen-printing substrates. Modified gelatin film was prepared by crosslinking with various crosslinking agents and the electrode array was designed by screen-printing. It was observed that the swelling ratio of C-2, crosslinked with glutaraldehyde and EDC/NHS (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide) was found to be lower (3.98%) than that of C-1 (crosslinked with only glutaraldehyde) (8.77%) and C-0 (without crosslinking) (28.15%). The obtained results indicate that the swelling ratios of both C-1 and C-2 were found to be lower than that of C-0 (control one without crosslinking). The Young’s modulus for C-1 and C-2 was found to be 8.55 ± 0.57 and 23.72 ± 2.04 kPa, respectively. Hence, it was conveyed that the mechanical strength of C-2 was found to be two times higher than that of C-l, suggesting that the mechanical strength was enhanced upon dual crosslinking in this study also. The adhesion study indicates that silver ink adhesion on the gelation surface is better than that of carbon ink. In addition, the electrical response of C-2 with a screen-printed electrode (SPE) was found to be the same as the commercial polycarbonate (PC) substrate. The result of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay suggested that the silver SPE on C-2 was non-cytotoxic toward L929 fibroblast cells proliferation. The results indicated that C-2 gelatin is a promising material to act as a screen-printing substrate with excellent biodegradable and biocompatible properties.

Blood glucose monitoring is a valuable tool for managing diabetes. In recent years, with the increase of diabetics in the world, continuous glucose monitoring (CGM) of blood sugar changes has attracted more and more researchers' attention. Among the current technologies for measuring glucose, optical and electrochemical glucose sensors are the mainstream. Here, we introduce the history of optical, electrochemical, and other sensors such as field effect transistor sensors and their advantages and disadvantages, respectively. This review summarizes the research progress and main challenges of continuous glucose monitoring technology. We found that different optical techniques have different limitations which restricts the development of optical CGM. In contrast, electrochemical glucose sensors are more feasible and reliable in implementing CGM. Therefore, this review focuses on the development and shortcomings of electrochemical sensors, especially the promising direct electron transfer and the current commercial CGM. Hopefully, it will help readers sort out the future of CGM's development.

Surface plasmon resonance (SPR) is a real-time, label-free, and high-sensitive detection technology. SPR has been widely used in many applications such as biomolecular interaction analysis, environmental monitoring, and medical diagnostics. However, conventional SPR sensor systems usually require expensive equipment and complicated optics. In this paper, we have demonstrated a rapid prototyping of angle-scanning SPR for bioanalytical investigation. Rapid prototyping was attained by utilizing the FDM (fused deposition modeling) based 3D (three-dimensional) printing technology. Two rotating platforms were employed to drive the laser source and photodiode, respectively. A temperature regulation unit was incorporated to maintain the system temperature in order to reduce the temperature effect. The proposed SPR rapid prototyping yielded a refractive index resolution of 6.4×10 −6 RIU (refractive index unit), and the biotin-avidin system validated the kinetics parameters measurement capability. The obtained results indicated that the FDM 3D printing has great potential for developing rapid-prototyping SPR system.