Abstract Determination of blood glucose level is a frequently occurring procedure in diabetes care. As the most common method involves collecting blood drops for chemical analysis, it is invasive and liable to afflict a degree of pain and cause a skin injury. To eliminate these disadvantages, this thesis focuses on pulsed photoacoustic techniques, which have potential ability in non-invasive blood glucose measurement. The fundamental theory of photoacoustics in liquid and soft tissue was studied systematically. The distributions of photoacoustic sources in a near-infrared optical skin model were simulated by the Monte Carlo method. Expansion coefficient and specific heat of glucose solution were measured by thermodynamic method, while the sound velocity in it was determined by photoacoustic approach. The effect of glucose on blood optical scattering was studied by a picosecond pulsed laser together with a streak camera. A photoacoustic apparatus comprising a pulsed laser diode and a piezoelectric transducer was built and applied to measure glucose concentration in water and scattering media. Moreover, this apparatus was also used to non-invasive experiment on human fingers. The measurements showed that the expansion coefficient, specific heat and acoustic velocity change by 1.2%, -0.6% and 0.28%, respectively, in response to a 1% change in glucose concentration. The sum effect of these parameters to photoacoustic signal was much larger than that of optical absorption of glucose in near infrared wavelengths, which provided photoacoustic technique a higher degree of sensitivity than offered by the optical absorption method. At the wavelength of 905 nm, the measured glucose detection sensitivity in a 3% milk solution, a tissue sample and whole human blood was 5.4%, 2.5% and 14%, respectively. Each figure is higher than that of glucose in water, about 2%, for a one percent change in glucose concentration. This was supported by the temporal dispersion curves of glucose in blood samples, which demonstrated that glucose decreased the optical scattering of tissues. The currently photoacoustic apparatus could detect the minimal glucose concentration of 100 mg/dl in whole blood samples. It is sensitive to physiological changes in non-invasive measurement, but insufficient for evaluating change in the physiological glucose concentration. Current photoacoustic techniques have apparently advantages in study of scattering media and made great progress in tissue imaging and diagnosis. However, in non-invasive blood glucose measurement they met similar problems as optical approaches based on scattering effect.

Abstract The development of a non-invasive glucose monitoring technique is very important because it would tremendously diminish the need to puncture the skin when taking blood samples and help diabetic patients in controlling their blood glucose levels and in treating Diabetes Mellitus. The focus of this thesis is on measuring the effect of glucose on the light scattering properties of a tissue-simulating phantom and biological tissues in vitro. Optical coherence tomography (OCT), the pulsed photoacoustic (PA) technique, and the time-of-flight (TOF) technique are used in the measurements and their capabilities for detecting changes in the scattering properties are evaluated and compared with each other. The theoretical background of the techniques, light propagation and PA wave generation are briefly explained. The glucose-induced changes in light scattering are also reviewed. The measurement results with the OCT and the PA technique from Intralipid, pig whole blood, and mouse skin tissue samples show that the glucose-induced changes are larger in the biological tissues than in the Intralipid phantom. The PA measurements show that although the PA signals are stronger at a wavelength of 532 nm than at 1064 nm, the glucose-induced change in the peak-to-peak value of the PA signal measured from pig whole blood is larger at a wavelength of 1064 nm than at 532 nm. The TOF measurements with a streak camera show that the scattering-related changes in the registered pulse shapes occur mainly in the rising part of the pulses. The utilization of fiber-optic measurement heads enabled the detection of back-scattered photons at different distances from the emitting fiber. Although all the techniques are able to detect changes induced by large glucose concentrations (0–5000 mg/dl) in Intralipid, the effect of glucose on the scattering properties of Intralipid is so weak that the techniques failed to detect changes with lower (50–500 mg/dl) concentrations. The measurements of biological samples with the PA technique and with the OCT also demonstrate capabilities to measure glucose concentrations in the physiologically relevant range (18–450 mg/dl) as well. The results compare well with earlier literature and also confirm some earlier findings.