Elsevier

Biosensors and Bioelectronics

Volume 72, 15 October 2015, Pages 370-375
Biosensors and Bioelectronics

U-shaped fiber-optic ATR sensor enhanced by silver nanoparticles for continuous glucose monitoring

https://doi.org/10.1016/j.bios.2015.05.023Get rights and content

Highlights

  • 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.

Abstract

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.

Introduction

Diabetes mellitus is a serious human disease, and it is important to monitor blood glucose levels continuously to provide guidance for diagnosis and therapy. To date, the implantable enzyme electrode sensing technique is the only method that has been used in clinical settings for continuous glucose monitoring by measuring the electric current generated by enzyme reactions in subcutaneous tissue (Oliver et al., 2009). The representative products include SEVEN® Plus (DexCom, Inc.) (Zisser et al., 2009), Paradigm® REAL-Time (Medtronic, Inc.) (Deiss et al., 2006) and FreeStyle Navigator® (Abbott Laboratories) (Weinzimer et al., 2008). However, the significant drift caused by bioelectricity and the effect of electrochemical reactions under hypoxia reduce the accuracy of glucose monitoring. Therefore, finger-prick blood corrections are often required to calibrate enzyme-based glucose sensors several times each day. In addition, the local glucose level close to the enzyme electrode is irreversibly depleted by the glucose oxidase enzyme reaction, resulting in a measured glucose value that is lower than the true concentration. Especially, it is difficult to detect the hypoglycemia effectively using enzyme electrode based sensors, which is still a big challenge for continuous glucose monitoring in clinics. The fluorescence-based glucose sensors have ever showed its potential for glucose in vivo (He et al., 2014). However, this method is vulnerable for slow response time and poor long-term stability of fluorescent molecules. Also biomolecules similar to glucose may cause interferes and give false positives. The surface-enhanced Raman scattering (SERS), a very promising technique for glucose sensing, has been investigated for glucose determination in physiological concentration range (Chanda et al., 2004, Kong et al., 2014). However, the biggest challenge of this technique of how to miniaturize the SERS-active surface and fabricate active substrate on the tip of a fiber-optic probe for implantable glucose determination.

The glucose “finger print” band has been successfully applied for direct glucose monitoring in vitro from bio-fluid with complex components such as blood, interstitial fluid (ISF) and dialysis solution by mid-infrared ATR spectroscopy (Diessel et al., 2005; Lambrecht et al., 2006; Roychoudhury et al., 2006). At the same time, the fiber-based technique provides an excellent approach to fabricate small ATR sensors, which makes it possible to implant the sensors into subcutaneous tissue for continuous glucose monitoring (Yu et al., 2014). Compared with enzyme electrode sensors, only light was allowed to pass though the implantable fiber-optic sensor under the skin, therefore the glucose monitoring using fiber-optic sensors is not affected by bioelectricity in the body. The glucose “finger print” absorption peaks were used for specific glucose monitoring instead of oxidase enzyme, so the affection of glucose depleted by enzyme reaction was avoided, then it is possible to detect the hypoglycemia which will bring deadly dangerous for diabetics, and the glucose concentration measured is more consistent with the actual value. Compared with the fluorescence-based glucose sensor, the sensor fabricated in this paper need not be banded to any fluorescent molecules and the specific absorbance in the mid-infrared band allows a substance to be distinguished from various chemical species. These characteristics make the fiber-optic ATR sensor more suitable and promising for implantation in tissue for continuous glucose monitoring. However, low sensitivity and resolution are concomitant with the miniaturization of the fiber-optic ATR sensor.

To improve the sensitivity and monitoring resolution of fiber-optic ATR sensor, a U-shaped fiber-optic ATR sensor was fabricated in this study. The bent structure was constructive to increase the sensing optical length of the fiber-optic sensor in a limited space for implantable glucose measurement (Raichlin and Katzir, 2008). Compared with those of the conventional straight fiber-optic ATR sensor, each penetration depth and the total number of reflections were both increased after the fiber was bent (Artyushenko et al., 2008). Thus, the sensitivity and measurement resolution were improved.

Further, the silver nanoparticles were used to modify the surface of the U-shaped fiber-optic ATR sensor to enhance the infrared absorption of glucose. The absorption spectrum of the molecules near the nanoparticles was enhanced by a phenomenon exploited in ATR surface-enhanced infrared absorption (SEIRA) spectroscopy (Huo et al., 2009, Schnell et al., 2009). Unlike SERS, SEIRA spectrum was insensitive to the size and shape of nanoparticles. Aroca has investigated the enhanced factors of different metal nanoparticles and their SEIRA spectrums show no wavelength shift (Aroca, 2006). Thus, how to prepare SEIRA-active nanoparticles on the surface of sensor and improve the enhanced factor is the most concerned focus in SEIRA study. To date, studies of ATR-SEIRA only concentrated on a plane substrate (Enders et al., 2011, 101, Yan et al., 2008). Metal nanoparticles on crystalline ATR cells have been prepared through physical vapor deposition (PVD) or other deposition method (Renoirt et al., 2014, Sanchez-Cortes et al., 2001), electrode deposition methods (Magagnin et al., 2002) or wet chemical methods (Rao and Yang, 2011). However, it is a great challenge to grow metal nanoparticles with required size and distribution on the cylindrical surface of silver halide fibers and even more so to grow them on the bent fibers. In this study, the silver nanoparticles were fabricated on cylindrical surface of U-shaped fiber ATR sensor based on its silver halide material reduction directly without any preliminary nanoparticles synthesis and the following covalent bond or self-assembly for the first time. In the process of chemical reduction, glucose was employed as the reducing agent, the material of fiber ATR sensor is made of AgCl and AgBr which could offer silver ions by itself. This method provides a new way to fabricate nanoparticles on cylindrical surface of the fiber sensor based on silver halide materials.

Section snippets

Structure of implantable fiber-optic ATR sensor

As shown in Fig. 1, the silver-nanoparticle-enhanced fiber-optic ATR sensor can be implanted into subcutaneous tissue for continuous glucose monitoring. A biocompatible semipermeable membrane with a selectable molecular weight cut-off was used as a protective cover to separate the implanted sensor from the tissue, filter out large biological molecules within the ISF and allow glucose molecules to pass through. The sensor was fabricated in two main steps: (1) the design of the bent,

Method of silver nanoparticles preparation

Glucose was employed as the reducing agent, and the chemical reduction reaction between ions in the fiber material can be expressed as follows (Rao and Yang, 2011):Ag+Cl+Ag+Br+CH2OH(CHOH)4CHO+NaOHAg+CH2OH(CHOH)4COOH+Na+Cl+Na+Br

The concentration of glucose with aldehyde groups (–CHO) is very low (Supplementary Fig. 1). However, the silver ions can be reduced by –CHO at normal temperature in alkaline solution (PH value varies around 12), which strongly influences the nanoparticles morphology

Experimental set-up

A dual-path laser-measurement set-up was established for glucose monitoring using a tunable CO2 laser and fiber-optic ATR sensor (Supplementary Fig. 2). An infrared attenuator (Model 401, Lasnix, Berg, Germany) was used to attenuate the high laser output power (maximum power of 800 mW) to a reasonable level. The attenuated laser beam was divided into dual paths by a zinc selenide (ZnSe) beam splitter (BS), one for reference and the other for sample measurement. The dual-path incidence laser

Conclusions

In this study, a method for continuous glucose monitoring based on a silver-nanoparticle-enhanced bent fiber-optic ATR sensor in combination with a tunable mid-infrared laser was proposed for the first time. A U-shaped fiber-optic ATR sensor with a radius of 2.5 mm was fabricated, on which silver nanoparticles were prepared to enhance the sensitivity of the sensor using a chemical reduction method without any preliminary nanoparticles synthesis and the following covalent bond or self-assembly.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 61176107513501102331120421061428402 and 61201039), the Key Projects in the Science and Technology Pillar Program of Tianjin (No. 11CKFSY01500), the Key Program of Tianjin Natural Science Foundation (No. 15JCZDJC36100), the National Key Projects in Non-profit Industry (No. GYHY200906037), the National High Technology Research and Development Program of China (No. 2012AA022602), and the 111 Project of China

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