Abstract

Because mid-infrared (mid-IR) spectroscopy is not a promising method to noninvasively measure glucose in vivo, a method for minimally invasive high-precision glucose determination in vivo by mid-IR laser spectroscopy combined with a tunable laser source and small fiber-optic attenuated total reflection (ATR) sensor is introduced. The potential of this method was evaluated in vitro. This research presents a mid-infrared tunable laser with a broad emission spectrum band of 9.19 to 9.77[Formula: see text](1024~1088 cm(-1)) and proposes a method to control and stabilize the laser emission wavelength and power. Moreover, several fiber-optic ATR sensors were fabricated and investigated to determine glucose in combination with the tunable laser source, and the effective sensing optical length of these sensors was determined for the first time. In addition, the sensitivity of this system was four times that of a Fourier transform infrared (FT-IR) spectrometer. The noise-equivalent concentration (NEC) of this laser measurement system was as low as 3.8 mg/dL, which is among the most precise glucose measurements using mid-infrared spectroscopy. Furthermore, a partial least-squares regression and Clarke error grid were used to quantify the predictability and evaluate the prediction accuracy of glucose concentration in the range of 5 to 500 mg/dL (physiologically relevant range: 30~400 mg/dL). The experimental results were clinically acceptable. The high sensitivity, tunable laser source, low NEC and small fiber-optic ATR sensor demonstrate an encouraging step in the work towards precisely monitoring glucose levels in vivo.

Highlights

  • The blood glucose level of diabetic patients should be closely monitored to provide guidance values for medication or insulin injection

  • This paper introduces a minimally invasive method to determine the glucose level in vivo using mid-IR spectroscopy in combination with a tunable carbon dioxide (CO2) laser and small fiber-based attenuated total reflection (ATR) sensor

  • The application of tunable wavelength CO2 laser spectroscopy based on fiber-optic ATR sensors to determine the glucose concentration over a physiologically relevant concentration range was reported in this study and demonstrated promising results

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Summary

Introduction

The blood glucose level of diabetic patients should be closely monitored to provide guidance values for medication or insulin injection. The strong absorption of water in the band has been the biggest challenge for noninvasive glucose detection in vivo using mid-IR light. The C-C bending vibrations at 1035 cm 1 and 1077 cm 1 (and/or symmetric stretch of PO2- at 1080 cm 1, C-OP stretch at 1047 cm 1) in the spectrum of human skin do relate to glucose, as the glucose C-C bands are a minor component compared with those of the other chemical components of tissue, such as proteins and fats [9, 10] These interferences of absorption peaks due to vibrations and/or stretches from other skin components pose a significant challenge to the noninvasive measurement of glucose in vivo using scattering light in the mid-IR band. Reports that detail the measurement of glucose in vivo using this method have not been published

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