Evaluation of Opportunities and Limitations of Mid-Infrared Skin Spectroscopy for Noninvasive Blood Glucose Monitoring

Abstract

Background: A wide range of optical techniques has recently been presented for the development of noninvasive methods for blood glucose sensing based on multivariate skin spectrum analysis, and most recent studies are reviewed in short by us. The vibrational spectral fingerprints of glucose, as especially found in the mid-infrared or Raman spectrum, have been suggested for achieving largest selectivity for the development of noninvasive blood glucose methods.

Methods: Here, the different aspects on integral skin measurements are presented, which are much dependent on the absorption characteristics of water as the main skin constituent. In particular, different mid-infrared measurement techniques as realized recently are discussed. The limitations of the use of the attenuated total reflection technique in particular are elaborated, and confounding skin or saliva spectral features are illustrated and discussed in the light of recently published works, claiming that the attenuated total reflection technique can be utilized for noninvasive measurements.

Results: It will be shown that the penetration depth of the infrared radiation with wavelengths around 10 µm is the essential parameter, which can be modulated by different measurement techniques as with photothermal or diffuse reflection. However, the law of physics is limiting the option of using the attenuated total reflection technique with waveguides from diamond or similar optical materials.

Conclusions: There are confounding features from mucosa, stratum corneum, or saliva, which have been misinterpreted for glucose measurements. Results of an earlier study with multivariate evaluation based on glucose fingerprint features are again referred to as a negative experimental proof.

Keywords: attenuated total reflection; in vivo spectroscopy; mid-infrared spectroscopy; noninvasive blood glucose assays; penetration depth simulation; skin and oral mucosa.

Figure 1.

(a) Close-up on the fiber-optical probe head with the embedded diamond prism and silver halide fibers for waveguiding. The schematic diagram provides insight into the ATR measurement principle; (b) photo of the fiber-only probe head with a U-shaped fiber element for reproducible skin surface measurements with schematics for evanescent wave sensing. All fiber-optical probes were assembled at infrared fiber sensors (Aachen, Germany). ATR, attenuated total reflection.

Figure 2.

(a) Microscopic cross-sections of surface skin tissue from the outer lip; (b) epidermal oral mucosa from the inner lip with blood vascular information.

Figure 3.

Calculated penetration depths d_p of the evanescent wave and the reflectances R_s, R_p, and R_eff for the diamond/air (a) and the diamond/water (mucosa) (b) interfaces at 1000 cm⁻¹ plotted vs the different angles of reflection (n_air = 1.0, n_diamond = 2.42, ñ_tissue = 1.2085 + i 0.0541 at a wavenumber of 1000 cm⁻¹).

Figure 4.

(a) Comparison of the sensitivities obtained with transmission- and ATR-spectroscopy, as demonstrated by aqueous glucose measurements; (b) ATR spectra of pure saliva and saliva measured against water for the accentuation of the sample phosphate showing up in the spectral signatures around 1075 cm⁻¹. ATR, attenuated total reflection.

Figure 5.

(a) IR-ATR spectra of different human skin tissues, also after ethanol cleansing, measured with a fiber-optic probe, as well as water for comparison, indicating varying H₂O absorption signatures within each recorded spectrum; (b) average stratum corneum spectra, representing four different skin classes after a hierarchical cluster analysis. Main spectral characteristics from the surface keratin-containing skin layer can be identified from the highlighted band interval (* lipid impurities from skin surface). ATR, attenuated total reflection; IR, infrared.

Figure 6.

(a) Four fiber-probe spectra, recorded from the back of a human hand before and after different pretreatments of the skin site; (b) Forearm skin spectra after multiple tape strippings with an apparent increase of water absorption.