Laser photoacoustic studies of glucose in human tissue

Jonas Kottmann and Markus W. Sigrist

Goals of the project

The objective of the study is the development of a laser-based photo-acoustic device, which is able to measure glucose concentration in vitro and in vivo at a level in the physiological range. This research should contribute towards the development of a non-invasive glucose sensor which would circumvent the need of daily blood sample taking for diabetic patients.

Introduction

Photoacoustic spectroscopy (PAS) of solids

For photo-acoustic signal generation a sample is irradiated with either amplitude-modulated or pulsed light. The molecules of interest present in the sample absorb radiation of a characteristic part of the spectrum and convert the incoming optical energy into periodic heating of the sample by means of non-radiative relaxation processes. This leads to a modulated volumetric expansion and to the propagation of a thermal and acoustic wave inside the sample. The acoustic wave can be detected either with a microphone in the coupling gas within a photoacoustic cell placed on the sample surface or with a piezoelectric transducer in direct contact with the sample surface. The mechanism of PA signal generation is depicted in Fig. 1.

Mid-infrared (MIR) spectroscopy 

The MIR region (5-25 μm) of the spectrum is particularly attractive for studies of biological samples since most molecules have a characteristic absorption spectrum in this wavelength range. PAS is especially interesting for biomedical studies since it is (i) noninvasive (for moderate laser intensities), (ii) much less influenced by scattering effects than alternative optical techniques, and (iii) readily adaptable to the study of biological tissues. The MIR region has the big advantage that the glucose spectrum does not interfere as much with other blood and tissue constituents as it does in the near infrared and it shows distinct absorption maxima. However water as the main constituent of the human body tissue absorbs very strongly in the MIR and leads to penetration depths of less than 100 µm depending on the measurement site. These two aspects make the detection of glucose challenging.

Experimental

Different cell designs and detection schemes for photo-acoustic measurements were tested using a CO₂ laser (930 cm^-1 - 1090 cm^-1) and first test measurements on glucose solution in water have been performed. An example of a preliminary cell construction is shown in Fig. 2. With the goal of minimizing the setup size using a QCL (quantum cascade laser) at a later stage of the project the optimal working frequencies in the mid-infrared are also investigated. 

Related papers

A. Rosencwaig: "Photo-acoustic spectroscopy of solids" Rev. Sci. Instrum. 48, 1133-1137 (1977).

H. von Lilienfeld-Toal, M. Weidenmüller, A. Xhelaj, and W. Mäntele: "A novel approach to non-invasive glucose measurement by mid-infrared spectroscopy: The combination of quantum cascade laser (QCL) and photoacoustic detection", Vib. Spectrosc. 38. 209 –215 (2005).

S.D. Campbell: "Applications of Photoacoustic Spectroscopy to Problems in Dermatology Research." IEEE Trans. Biomed. Engin. 26, 220-227 (1979).

.

This study is financially supported and performed in cooperation with