Photoacoustic sensor for non-invasive in-vivo measurement of blood glucose
Diabetes is a widespread disease, which more and more takes on a dramatic scale. As of 2014 about 9% of the world’s population, increasingly also children and juveniles, suffer from diabetes [1-3]. Patients have to measure their blood glucose level several times each day in order to be able to make decisions concerning food ingestion and insulin dosage. The current method requires extracting small amounts of blood, which are applied on electrochemical test strips and analyzed with the aid of optical or electronical means. This procedure has severe disadvantages: Firstly, the necessity of pricking the skin results in a reduction of the quality of life of the patients and the methods bears the risk of inducing infections. Secondly, the test strips represent a considerable financial burden for the public health system. Physicians would recommend to measure the blood glucose level more often, but due to the disadvantages mentioned above this is currently not feasible.
Lately there are methods for the continuous determination of the blood glucose level available, which do not need the extraction of blood [4-6]. However, these procedures require the insertion of the sensor into the body tissue and, therefore, suffer from related inconveniences concerning the quality of life and the risk of infections. In addition, the sensors have to be replaced after relatively short periods of time. The related costs are substantial.
Proposals for a non-invasive optical measurement of the glucose level have been discussed for several years. One idea is to excite the glucose molecules with laser radiation. Glucose molecules strongly absorb electromagnetic radiation in the mid-infrared wavelengths region. However, since this type of radiation is also strongly absorbed by water molecules, its penetration depth in the epidermis is only ca. 50 to 100 micrometers and it does not reach blood vessels. Glucose molecules are transported from blood to the interstitial fluid contained in the outer skin layers by passive diffusion, where in principal it can be detected. Radiation energy absorbed by the glucose molecules results in a slight heating of the irradiated region. Sensors based on the photoacoustic effect apply modulated radiation. This leads to a periodic heating and, therefore, to a periodic pressure variation, i.e. a sound wave. The sound wave can be detected with a microphone.
The feasibility of photoacoustic sensors for the non-invasive in-vivo measurement of the blood glucose level has been demonstrated . Glucose concentrations of 50 mg/dl have been detected applying a measuring time of 5 s. Since the glucose concentration in human blood is in the range of ca. 30 to 500 mg/dl, the detection sensitivity has to be considerably enhanced before the method can be used for a clinical application .
The aim of the project is to obtain a higher sensitivity by using a photoacoustic sensor with an optimized design of the acoustic resonator, resulting in a higher quality factor. For the conduction of the corresponding parameter studies numerical methods are in respect of efficiency and costs superior to experiments since the calculation of the signal strength requires relatively little effort, once a verified and validated model is available. In particular because of its flexibility concerning the shape of the domain, the modelling shall be based on the finite-element method. The improved resonator design, resulting from the shape optimization, has to be tested experimentally for its suitability to detect small concentrations of glucose molecules in the interstitial fluid. Finally, in cooperation with the Institute for Biophysics of the Goethe University Frankfurt, the sensor design shall be tested in clinical studies.
 M. A. Pleitez, T. Lieblein, A. Bauer, O. Hertzberg, H. von Lilienfeld-Toal, and W. Mäntele, „Windowless ultrasound photoacoustic cell for in vivo mid-IR spectroscopy of human epidermis: Low interference by changes of air pressure, temperature, and humidity caused by skin contact opens the possibility for a non-invasive monitoring of glucose in the interstitial fluid“, Rev. Sci. Instr., 84, 084901 (2013).
Special issue of Bioengineering