Noninvasive Glucose Measurements Through Transcutaneous Raman Spectroscopy: A Review

Abstract

Background: People living with diabetes need constant glucose monitoring to avoid health complications. However, they do not monitor their glucose levels as often as recommended, probably because glucose measurement devices can be painful, costly, need testing strips or sensors, require lancing the finger or inserting a sensor with risk of infection, and can be inaccurate or have failures. Therefore, developing new alternatives for noninvasive glucose measurements that overcome these disadvantages is necessary, being Raman spectroscopy (RS) a solution.

Objective: This review aims to provide an overview of the current glucose-monitoring technologies and the uses and advantages of RS to improve noninvasive transcutaneously glucose-monitoring devices.

Results: The skin has been used to assess glucose levels noninvasively because it is an accessible tissue where glucose can be measured in the interstitial fluid (ISF) in the epidermis (especially in the stratum corneum). The most selected skin sites to apply RS for noninvasive glucose measurements were the nailfold, finger, and forearm because, in these sites, the penetration depth of the excitation light can reach the stratum corneum (10-20 µm) and the ISF. Studies found that RS is a good optical technique to measure glucose noninvasively by comparing glucose levels obtained by RS with those from invasive methods such as glucose meters with testing strips during an oral glucose tolerance test (OGTT).

Conclusions: New alternatives for noninvasive glucose measurements that overcome the disadvantages of current devices is necessary, and RS is a possible solution. However, more research is needed to evaluate the stability, accuracy, costs, and acceptance.

Keywords: Raman spectroscopy; glucose monitoring; noninvasive; transcutaneous measurements.

Figure 1.

Description of how Raman spectroscopy works to provide a possible diagnosis: (1) Biofluids are obtained and put on a substrate (aluminum). (2) The samples are analyzed with Raman spectroscopy to obtain Raman spectra. (3) The spectra are analyzed by multivariate analysis. (4) If there are differences in the spectra and groups are separated, then the study sample can be differentiated into healthy and people with diabetes. Colored version is available online.

Figure 2.

Summary of Raman spectroscopy as a tool for glucose monitoring on skin: (a) Raman spectroscopy functions as a monochromatic light to detect glucose on skin, (b) the skin layers, (c) skin having scattering and absorbing compounds, and (d) skin sites used to apply Raman spectroscopy to assess glucose in the studies included in the review. Colored version is available online.

Figure 3.

Custom-built confocal Raman spectrometer. It explains how the Raman spectrometer works to assess the glucose onto the thenar (base of the thumb). Colored version is available online. Source: The image was adapted from Lundsgaard-Nielsen et al.