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

Abstract

<jats:sec><jats:title>Background:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> 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. </jats:p></jats:sec>

Recent Progress and Perspectives on Non-Invasive Glucose Sensors

“…Glucose sensing in the MIR has been demonstrated in aqueous solution, serum and human subjects [44,45] using MIR quantum cascade lasers, and it was found that 84% of results were within the clinically acceptable region of the Clarke analysis grid [46]. Attenuated total reflection (ATR) MIR was used with a three-wavelength model to obtain high accuracy results in the Clarke grid [47], however, another study found that ATR was unlikely to be effective due to the poor penetration of MIR light (up to 10 µm) and further confounding factors [48]. The penetration depth of MIR and the consequently short path length is the primary limitation of this wavelength range compared to the near infrared region.…”

Is Raman the best strategy towards the development of non-invasive continuous glucose monitoring devices for diabetes management?

“…Another device (under development in Tohoku University, Japan) is a minimally invasive device applicable on the inner lips, harnessing an attenuated total internal multireflection geometry ( Kino et al, 2016 ; Villena Gonzales et al, 2019 ). However, the use of attenuated total reflection for this kind of measures has been criticized due to penetration depth limitations ( Delbeck and Heise, 2021 ).…”

Non-invasive sensing techniques for glucose detection: a review

“…The required penetration depths for glucose detection are obtained using a quantum cascade laser (QCL), a semiconductor material divided into injecting and active regions [5]. Delbeck and Heise [13] presented their research based on a multivariate skin spectrum analysis. To achieve the largest selectivity for the development of non-invasive blood glucose method, they used the vibrational spectral fingerprint of glucose that is usually found in Mid-infrared spectroscopy.…”