In vitro glucose measurement using tunable mid-infrared laser spectroscopy combined with fiber-optic sensor

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.

A single-loop fiber attenuated total reflection sensor enhanced by silver nanoparticles for continuous glucose monitoring

“…In our study, the wavelength tunable CO 2 laser was customized from Access Laser Co. in Washington in USA. The emission wavenumbers were tuned by linear motor to rotate a grating, and the frequency and power of the tuned lines were stabilized using a photoelectric detection feedback system and a piezo actuator to modulate the cavity length [41]. In this study, the CO 2 laser achieved line tuning over the band of 9.19-9.77 m; five emission wavenumbers around the glucose absorption peaks 1080 and 1035 cm −1 , including 1081, 1076, 1051, 1041 and 1037 cm −1 were selected as working wavenumbers for glucose specific determination [16].…”

“…The emission wavenumbers were tuned by linear motor to rotate a grating, and the frequency and power of the tuned lines were stabilized using a photoelectric detection feedback system and a piezo actuator to modulate the cavity length [41]. In this study, the CO 2 laser achieved line tuning over the band of 9.19-9.77 m; five emission wavenumbers around the glucose absorption peaks 1080 and 1035 cm −1 , including 1081, 1076, 1051, 1041 and 1037 cm −1 were selected as working wavenumbers for glucose specific determination [16]. The five wavenumbers between the two absorption wavenumbers (1035 cm −1 and 1080 cm −1 ) could be tuned randomly in the theory, but after lots of experiment we found that the five wavenumbers (1081, 1076, 1051, 1041 and 1037 cm −1 ) which we selected can achieve both high stability of line frequency and power simultaneously compared to other wavenumbers.…”

“…First, fiber sensing is based on optical signals and the measurement is not affected by bioelectricity caused by electrochemical reactions in the body; thus, the signal drift would be reduced greatly and result are more accurate [14]. Second, five emission wavenumbers around the glucose absorption peaks were employed for glucose specific determination, as opposed to specificity of enzyme [15,16]; thus, no glucose was depleted during the measurement. In this case, hypoglycemia will not be missed, which is very important for continuous glucose monitoring.…”

Prediction of Glucose Concentration in a Glucose-Lactose Mixture Based on the Reflective Optical Power at Dual Probe Wavelengths

“…To mitigate these issues, optical detection schemes have been adopted for their salient features, including an enzyme-free process, fast response, and the potential for noninvasive detection. Absorption spectroscopy based on Beer's Law assumes a linear relationship between glucose concentration and absorbance [9][10][11][12][13][14], which is only good for concentrations below hundreds of mg/dL [15]. It has been noted that a bulky, expensive spectrometer is required to continuously monitor the absorption spectrum [10,12].…”

Blood glucose measurement by using hollow optical fiber-based attenuated total reflection probe

“…There have been many reports of applying MIR-ATR methods for blood glucose measurement including ones measuring glucose levels of whole blood, [8][9][10] urine, 11 and serum. 12,13 Some groups reported that they have attempted to measure blood glucose levels in vivo by using an ATR prism with MIR lasers 14,15 and an FT-IR spectrometer. 16 These methods mainly detect glucose in interstitial fluid that reflects the blood glucose level 17 because the penetration depth of MIR-ATR spectroscopy is limited to a few microns.…”