O. Abdallah, Q. Qananwah, A. Bolz
Institute of Biomedical Engineering IBT, Karlsruhe Institute of Technology KIT, Karlsruhe, Germany
J. Hansmann, S. Hinderer, and H. Mertsching
Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, University of Stuttgart, Stuttgart, Germany
Keywords: Fluorescence, Biosensors, Non-invasive glucose concentration monitoring, High signal to noise ratio,
Fluorescence spectroscopy, Glucose management, LASER for detection of glucose concentration.
Abstract: An easy accessible and low-cost method for glucose concentration monitoring and diabetes management
will be a great help for more than 250 millions of diabetic patients worldwide to avoid the risks and the
complications caused by hyper- or hypoglycemia. This paper shows the results obtained using fluorescence
spectroscopy for detecting the glucose concentrations in DMEM solutions. By irradiating DMEM solutions
that have different glucose concentrations with light, a few wavelengths in UV- and visible-range for the
calculations of glucose concentrations using fluorescence spectroscopy are applied and the detected signals
were analyzed. For the detection of glucose concentration noninvasively using various optical methods, the
interaction between light and definite glucose solutions was studied. The developed compact system will
enable the application of different LASER diodes (LD`s) or light emitting diodes (LED`s) in the range of
UV and NIR in an easy manner. Variable intensity, frequency and duty cycle can be adjusted for
fluorescence and other optical measurements. A multi-sensor taking all perturbations into account will be a
good choice for glucose monitoring. Fluorescence measurements at wavelengths below 800 nm and
especially the measurements at the wavelength 485 nm give reproducible glucose concentrations results
from DMEM glucose solutions at a constant temperature.
Continuous non-invasive monitoring of blood
glucose can achieve a great enhancement by glucose
management to attain a better normal life for
diabetics. Detection of blood contents like Glucose
non-invasively in an easy manner can reduce
morbidity and mortality by diabetics. Design of a
system for the detection of glucose in solutions and
non-invasively can be a great help for diabetics.
Diabetes risk lies in its complications like heart
diseases and infarcts, stroke, blindness, kidney
disease, nerve disease, diabetic foot and amputation.
The current applied invasive methods are
intermittent, inconvenient and painful, having
infection risk, blood loss and time delay, need
consumables materials, needles and strips. The
invasive method cannot be applied continuously, and
hence hypo- or hyperglycemia may be not detected.
A continuous blood glucose monitoring is essential
for glucose management. Noninvasive blood glucose
concentration monitoring will reduce mortality and
morbidity and improve life quality of more than 250
Million diabetic patients worldwide.
1.1 Fluorescence Spectroscopy
Glucose in water shows no fluorescence. In DMEM
solution a glucose dependent autofluoresence can be
observed. The fluorescence differs from the process
of Raman effect in that the incident light is
completely absorbed and the system is transferred to
an excited state from which it can go to various
lower states only after a certain resonance lifetime.
Abdallah O., Qananwah Q., Bolz A., Hansmann J., Hinderer S. and Mertsching H..
DOI: 10.5220/0003176504110414
In Proceedings of the International Conference on Biomedical Electronics and Devices (BIODEVICES-2011), pages 411-414
ISBN: 978-989-8425-37-9
2011 SCITEPRESS (Science and Technology Publications, Lda.)
Fluorescence spectroscopy and time resolved
fluorescence are now dominant methodologies and
used extensively not only in biochemistry and
biophysics, but also in biotechnology, medical
dioagnostics and genetic analysis (Moschou, 2004,
Pickup, 2005, Lakovics, 2006). The technique is
extremely sensitive. There are increasing examples
of even single-molecule detection using fluorescence
methods. Many studies indicate that fluorescent
technology has real sensitivity especially in low
glucose ranges. In addition, since near-infrared light
passes through several centimeters of tissue, with the
appropriate choice of fluorophore, molecules can in
theory be excited and the emission interrogated from
outside the body providing the potential for
completely non-invasive sensing. A convenient way
of classifying fluorescence-based glucose sensors
that involve measurements of fluorescence is either
according to the type of molecular receptor for
glucose, or whether cells or tissues are used to signal
glucose concentrations and/or glucose metabolism.
A review of the principles of operation and current
status of the various approaches to fluorescence-
based glucose sensing are described in D’Auria,
The results shown below are obtained using a
fluorescence spectrometer having the
stimulation/emission wavelengths of 360 nm
/465 nm, 430 nm / 535 nm and 485 nm / 535 nm.
The method discussed here will be applied for
invasive and non-invasive measurement.
Photodiodes or phototransistors for fluorescence
detection in the visible and NIR spectrum and light
emitting diodes LED or LASER diodes as light
sources will be applied. Variable frequency and duty
cycle can be adjusted for time resolved fluorescence
signal detection.
The block diagram of the principle of a flexible
developed measuring system is shown in Figure 1.
The developed system is flexible and can be used for
the development purposes, where different
parameters have to be adjusted. Then light
intensities, duty cycle, different LASER types and
variable amplifications can be achieved by using this
Figure 1: Block diagram of an optical sensitive measuring
The results obtained below by using a fluorescence
spectrometer show the emitted light by stimulation
of a DMEM solution with different glucose
concentrations. The detected signal with 465 nm by
the stimulation in the UV light at the wavelength of
360 nm is not highly correlated with the glucose
concentration (Figure 2). But an increasing tendency
of the emitted light with the increasing glucose
concentration is shown.
Figure 2: Fluorescence by stimulation/emission
wavelengths of 360 nm /465 nm.
The detected signal at 535 nm shows a high
correlation with glucose concentration when
stimulated with 485 nm (Figure 3). In the contrary to
the detected signals at 465 nm mentioned above, a
decreasing tendency of the emitted light with the
increasing glucose concentration is shown.
Figure 3: Fluorescence by stimulation/emission
wavelengths of 485nm /535 nm.
BIODEVICES 2011 - International Conference on Biomedical Electronics and Devices
Figure 4 shows also a high correlation of the
detected signal at 535 nm with known glucose
concentration when stimulated with 485 nm at
different glucose concentrations. We try here to
obtain a high resolution and accuracy at the lowest
normal level (about 50 g/dl) of glucose
concentrations in order to detect the hypoglycemia.
Also high accuracy has to be achieved around the
glucose concentrations of 180 g/dl in order to detect
hyperglycemia with an acceptable clinical accuracy.
Figure 4: Fluorescence by stimulation/emission
wavelengths of 485nm /535 nm.
Similar relationship between the detected signals
at the wavelength of 535 nm and the glucose
concentrations is shown in Figure 5 for stimulation
at the wavelength 430 nm. A decreasing tendency of
the emitted light with the increasing glucose
concentration is shown in Figure 4 and Figure 5.
Figure 5: Fluorescence by stimulation/emission
wavelengths of 430nm /535 nm.
The detected signal at 535 nm shows in
accordance to other measurements a higher
correlation with glucose concentration and a better
reproducibility when stimulated with 485 nm instead
of 430 nm.
Figure 6: Schematic of a multisensor for non-invasive
detection of blood glucose, hemoglobin concentration, and
fractional oxygen saturation.
The detected glucose signals are too small and
should be processed carefully. Also the in vivo
measurements are subjected to more noise and
motion artifacts. An adaptive filtering will be needed
for eliminating these perturbations. A Noise
Reference Signal is generated by means of a
Synthesizer or piezoelectric element and will be
adjusted as much as possible to the real noise
contained in the corresponding measurement by the
adaptive filter based on the least mean square
optimization algorithm. This algorithm has delivered
very good results by testing it for the non-invasive
calculations of oxygen saturation by artificial
vibrations of the hand, where a pulse oximeter
sensor is applied at the finger subjected to these
A non-invasive continuously blood glucose
concentration monitoring will improve the
management of diabetes mellitus. It will be
important for diabetics to avoid the complications
caused by high glucose level in blood. IR-
spectroscopy has the potential for the development
of a simple cost effective sensor for glucose
monitoring that can be used for home care.
Problems with existing methods have
encouraged alternative approaches to glucose
sensing, and those based on fluorescence intensity
and lifetime have special advantages, including
sensitivity and the potential for non-invasive
measurement when UV, visible or NIR light is used
(Yamakoshi, 2006; Evans, 2005; Evans, 2003;
Pickupa, 2005). The fluorescence signals using UV
100 100 300 500
0 100 200 300 400 500
GlucoseConcentration (mg/dl)
light as stimulus and detection of fluorescence at
violet or blue have shown a very good correlation
with the glucose concentrations in DMEM solution.
Light stimulation with blue light and the detection of
fluorescence by green region shows also a high
correlation with the glucose concentrations. The
detected glucose signals will be then subjected to
perturbations from the surroundings and from the
background of the measured locations due to tissue
alteration and physiological parameter variations.
All perturbations such as temperature, humidity and
applied pressure variations have to be included by
the calculations, as illustrated by Figure 6.
The drift of the characteristics of the electronic
and optical components may cause high disturbances
to the measurements. The integration of further
parameters may enhance the reproducibility but
decrease the accuracy due to the measurement
errors. The system complexity and the number of the
measured parameters have to be minimized.
There are few fluorescence-based glucose
detection methods that have reached the stage of
testing in vivo, but none have entered clinical
practice for diabetes management. This will be an
area of active investigation in a future work. We will
need to explore different interferences and the
stability as well as accuracy under normal life
There is no doubt that fluorescence technologies
have considerable promise for glucose sensing.
As a future work, all developed sensors will be
integrated in one system that enables the
simultenous processing of the detected signals
(Caduff, 2009). Other blood components like total
hemoglobin concentrations and fractional oxygen
saturation measured non-invasively have to be taken
as parameters by the glucose calculations. The
suitable locations for measurements may be earlobe
for transmission measurements or forehead as well
as abdomen for reflection measurements has to be
chosen. Applying the Twersky theory or diffusion
theory by the calculations are our next perspectives.
After that a clinical study for non-invasive
measurements and applying the neural fuzzy
techniques the results and the system will be
Using a daily, disposable contact lens embedded
with newly developed boronic acid containing
fluorophores may also be suitable for the continuous
monitoring of tear glucose levels.
This work is a part of the project „System for Non-
invasive Detection of Glucose “supported by the
Foundation Baden-Württemberg Stiftung by
Research Program: Microsystem technology for the
life sciences. We thank also Dr. Michaela Mueller
and Svenja Hinderer from Fraunhofer Institute
Institute IGB, University of Stuttgart for the
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BIODEVICES 2011 - International Conference on Biomedical Electronics and Devices