Microfluidic systems based on polydimethylsiloxane (PDMS) have gained popularity in recent years. However, microelectrode patterning on PDMS to form biosensors in microchannels remains a worldwide technical issue due to the hydrophobicity of PDMS and its weak adhesion to metals. In this study, an additive technique using inkjet-printed silver nanoparticles to form microelectrodes on PDMS is presented. (3-Mercaptopropyl)trimethoxysilane (MPTMS) was used to modify the surface of PDMS to improve its surface wettability and its adhesion to silver. The modified surface of PDMS is rendered relatively hydrophilic, which is beneficial for the silver droplets to disperse and thus effectively avoids the coalescence of adjacent droplets. Additionally, a multilevel matrix deposition (MMD) method is used to further avoid the coalescence and yield a homogeneous pattern on the MPTMS-modified PDMS. A surface wettability comparison and an adhesion test were conducted. The resulting silver pattern exhibited good uniformity, conductivity and excellent adhesion to PDMS. A three-electrode electrochemical biosensor was fabricated successfully using this method and sealed in a PDMS microchannel, forming a lab-on-a-chip glucose biosensing system.

•A borate polymer was bound to the SPR sensor to specifically determine glucose.•The affinity measurement does not consume glucose through reversible reaction.•Polymer layer number can be controlled to adjust measurement range and resolution.A novel surface plasmon resonance (SPR) sensor bound to the borate polymer PAA-ran-PAAPBA through a layer-by-layer method was proposed for the determination of glucose concentration. In contrast to the enzyme electrode sensor, the use of optical refractive index sensing to detect glucose concentration eliminates the measurement drift caused by bioelectricity when the sensor is implanted into subcutaneous tissue; in addition, a borate polymer was used to replace the glucose oxidase (GOD) enzyme and it does not consume the glucose molecule during measurement through the affinity reaction between the polymer and glucose. In this study, the layer-by-layer self-assembly method was used to immobilize the borate polymer on the surface of the SPR sensor. The effects of the number of layers are discussed in the manuscript, and the regenerability, reproducibility, and stability of the SPR sensor were evaluated. Almost all of the studies are performed under specific alkaline conditions (usually close to or higher than the pKa of PBA). And for the future application in vivo, we further investigated glucose detection at physiological conditions. The measurement resolution of the sensor bound to 12 polymer layers at physiological conditions was 1 mg/dL, and the R-squared value of the glucose concentration-ΔRU fitting curve within 1–1000 mg/dL was as high as 0.998, which indicates that this measurement may form the foundation of an implantable device for the continuous measurement of glucose concentration.

•Five glucose absorption wavelengths were emplyed for specific glucose detection to overcome the drawbacks of enzyme electrodes based glucose sensor.•Silver nanoparticles were prepared on the U-shaped fiberATR sensor to enhance the glucose sensing for implantable continuous glucose monitoring.•Fabrication of silver nanoparticles on cylindrical surface of fiber ATR sensor by chemical reduction of its silver halide materials directly was proposed.An implantable U-shaped fiber ATR sensor enhanced by silver nanoparticles on cylindrical surface was presented for continuous glucose monitoring to overcome the drawbacks of traditional glucose sensing technique based on enzyme electrodes. A U-shaped structure was addressed to increase effective optical length at limited implantable space to enhance the sensitivity of fiber ATR sensor. A novel method to fabricate silver nanoparticles on cylindrical surface of U-shaped fiber ATR sensor based on chemical reduction of its silver halide material directly without any preliminary nanoparticles synthesis and following covalent bond or self-assembly was proposed. Five glucose absorption wavelengths in the mid-infrared band were employed for specific glucose monitoring. The experimental results indicate that the sensitivity and resolution of the silver-nanoparticle-enhanced U-shaped fiber-optic ATR sensor are approximately three times those of a conventional one. The high sensitivity and low-noise performance makes it promising for in vivo glucose monitoring in the future clinical applications.

•Method of controlling and stabilizing tunable laser was proposed.•A novel, stable MIR tunable laser with broad emission spectrum was presented.•A novel small-sized flow-through fiber-optic ATR sensor was fabricated.•The noise-equivalent concentration is as low 3.8 mg/dL.•The sensitivity three times that of traditional FT-IR spectrometer was acquired.Wavelength-tunable laser spectroscopy in combination with a small-sized fiber-optic attenuated total reflection (ATR) sensor (fiber-based evanescent field analysis, FEFA) is reported for the continuous measurement of the glucose level. We propose a method of controlling and stabilizing the wavelength and power of laser emission and present a newly developed mid-infrared wavelength-tunable laser with a broad emission spectrum band of 9.19–9.77 μmμm (1024–1088 cm−1). The novel small-sized flow-through fiber-optic ATR sensor with long optical sensing length was used for glucose level determination. The experimental results indicate that the noise-equivalent concentration of this laser measurement system is as low as 3.8 mg/dL, which is among the most precise glucose measurements using mid-infrared spectroscopy. The sensitivity, which is three times that of conventional Fourier transform infrared spectrometer, was acquired because of the higher laser power and higher spectral resolution. The best prediction of the glucose concentration in phosphate buffered saline solution was achieved using the five-variable partial least-squares model, yielding a root-mean-square error of prediction as small as 3.5 mg/dL. The high sensitivity, multiple tunable wavelengths and small fiber-based sensor with long optical sensing length make glucose determination possible in blood or interstitial fluid in vivo.

Transdermal extraction of interstitial fluid (ISF) offers an attractive method for non-invasive blood glucose monitoring. In order to calculate blood glucose concentration accurately, precise volume measurement of transdermally extracted ISF is required due to human skin’s varying permeability. In this paper, we presented a novel flow sensor fabricated from polydimethylsiloxane (PDMS), designed to measure the volume of conductive liquid. The flow sensor consists of two pairs of metal electrodes, which are fabricated in the PDMS channel. The volume of liquid is measured utilizing the time-of-flight of the two electrode pairs’ resistance while the liquid is flowing through the flow sensor. 1–14 μL normal saline solution was measured, the flow sensor measured volumes correlate very well (R2 = 0.9996 and R2 = 0.9975 for vacuum pump and syringe pump situations respectively) with the actual volumes. And the coefficient of variation for 10 times 10 μL normal saline solution measurement is 0.0077 (vacuum pump) and 0.0381 (syringe pump), respectively. The demonstrated flow sensor provides excellent functionality for conductive liquid.

•An equipotential method was proposed to measure the normal skin impedance.•The impedance aimed at determining the volume of extracted interstitial fluid.•The method was verified by experiment comparing to the implanted electrode method.•The effects of humidity and pressure on the measurement accuracy were studied.Normal skin impedance, which has a good correlation with skin permeability, can be used to calculate the volume of extracted interstitial fluid. However, it is still very difficult to determine non-invasively the normal skin impedance. In this study, a novel non-invasive method based on equipotential theory for real-time, in vivo and accurate measurements of normal skin impedance was proposed. The suggested method was based on the theory of an equipotential between the saliva and interstitial fluid of an organism, and this method was compared with the method based on an implanted electrode. The effects of humidity and pressure on the measurement accuracy of normal skin impedance were also studied. The feasibility of this method was verified by the results of the experiments. The proposed method is expected to enhance the blood glucose prediction accuracy and demonstrates a huge significance for the minimally invasive measurements of blood glucose in clinical application.