Critical-depth Raman spectroscopy enables home-use non-invasive glucose monitoring

Abstract

One of the most ambitious endeavors in the field of diabetes technology is non-invasive glucose sensing. In the past decades, a number of different technologies have been assessed, but none of these have found its entry into general clinical use. We report on the development of a table-top confocal Raman spectrometer that was used in the home of patients with diabetes and operated for extended periods of time unsupervised and without recalibration. The system is based on measurement of glucose levels at a ‘critical depth’ in the skin, specifically in the interstitial fluid located below the stratum corneum but above the underlying adipose tissue layer. The region chosen for routine glucose measurements was the base of the thumb (the thenar). In a small clinical study, 35 patients with diabetes analyzed their interstitial fluid glucose for a period of 60 days using the new critical-depth Raman (CD-Raman) method and levels were correlated to reference capillary blood glucose values using a standard finger-stick and test strip product. The calibration of the CD-Raman system was stable for > 10 days. Measurement performance for glucose levels present at, or below, a depth of ~250μm below the skin surface was comparable to that reported for currently available invasive continuous glucose monitors. In summary, using the CD-Raman technology we have demonstrated the first successful use of a non-invasive glucose monitor in the home.

Evaluation of accuracy dependence of Raman spectroscopic models on the ratio of calibration and validation points for non-invasive glucose sensing

“…PLS modeling coupled with cross validation yielded encouraging results [23]. Weber et al developed a tabletop confocal Raman system to collect signals from interstitial fluid and tested this set-up on a group of 35 patients[24]. Even though results of these studies have provided substantial evidence in support of RS for monitoring glucose level one of the major hindrances in successful translation of spectroscopic glucose sensors for routine clinical usage is the unavailability of appropriate exit criterion for analyzing the unknown samples [21].…”

Review of Non-Invasive Glucose Sensing Techniques: Optical, Electrical and Breath Acetone

“…The vibrational modes for glucose molecules (C 6 H 12 O 6 ) are associated with C-O, C-C and C-H stretching bonds and are observed between 800 and 1200 cm −1 for C-O and C-C and around 2900 cm −1 for C-H [101]. Thus, typical glucose Raman fingerprints are observed at 911, 1060 and 1125 cm −1 , with the highest intensity Raman signal at 1125 cm −1 [28,102].…”

“…Non-invasive glucose Raman-based detection is possible with calibration stability of at least 10 days [102]. The measurement set up for this system includes an 830 nm light source irradiating at 250 µm below the skin surface (targeting the interstitial fluid region) of the thumb in 35 patients.…”

“…Analysis methods include partial least squares regression (PLS), principal component analysis (PCA), support vector machine (SVM) and backpropagation artificial neural network (BP-ANN). The first two methods can be applied as data compression techniques and the two latter methods can be used for finding both linear and non-linear relationships between the glucose concentration and the measured spectrum [102,[104][105][106].…”

Noninvasive Glucose Measurement Using Machine Learning and Neural Network Methods and Correlation with Heart Rate Variability

“…There are several research projects by LightTouch Medical, C8 Medisensors [58], and Massachusetts Institute of Technology applying the Raman spectroscopy method on skin [22]. Development of a Raman spectrometer suitable for home-use noninvasive glucose monitoring was also reported in [59] (v) Photoacoustic spectroscopy measures ultrasonic waves created by tissue absorption of pulsating light created by a laser diode [60], as their interaction generates heat and causes pressure variations in the sample in the form of acoustic signals monitored by a piezoelectric transducer [61]. A theoretical study of resonant photoacoustic 4 Journal of Sensors spectroscopy for noninvasive glucose detection was reported in [62].…”