Proceedings of the 8th IEEE GCC Conference and Exhibition, Muscat, Oman, 1-4 February, 2015
Noninvasive Blood Glucose Level Measurement
Using Nuclear Magnetic Resonance
AHMED Y. LUAIBI, AHMED J. AL-GHUSAIN, ASIF RAHMAN, MOHAMMAD H. AL-SAYAH, HASAN A. AL-NASHASH
American University of Sharjah, Sharjah, UAE, hnashash@aus.edu
Abstract— Many investigations have been conducted in the
field of noninvasive blood-glucose concentration measurement
yet; none seem to meet the standards of comfort, accuracy and
safety. This paper presents the preliminary outcomes of our
investigations into the potential of using nuclear magnetic
resonance (NMR) principles for the noninvasive measurement of
blood glucose level in humans. The initial phase of the research
involved testing the feasibility of using NMR in measuring
glucose concentration in water. Then, the method was modified
to enable us to measure the glucose level concentration in
humans. Various signal processing methods were tested to find
the best algorithm that improves detection accuracy. Results
obtained from two human subjects are used to demonstrate the
feasibility and found to be promising with error varying between
3% and 14%.
Keywords—noninvasive, glucose level, NMR, Diabetes
I. INTRODUCTION
The Glucose level in blood is a very important parameter
to measure, especially for people with diabetes. Currently, the
only way to measure a patient’s blood glucose level is by
puncturing the skin and extracting a sample of blood for
analysis. This invasive method is painful and causes
discomfort for diabetic patients who need to check their blood
glucose levels several times a day. Also, diabetic patients’
blood does not clot easily which leads to high risk of infection.
Furthermore, invasive methods require disposable test strips
that can be costly to the patient over very long periods of time.
In the last thirty years, there has been extensive research
efforts into creating a technique to measure blood glucose
levels without puncturing the skin, or noninvasively.
However, none of these attempts have created devices that are
safe and accurate. Therefore, there is a need for a new
approach to monitor blood glucose noninvasively. The nature
of this research is investigative; it will seek to explore the
validity of using a new method to find a solution to the
proposed problem. The current state of the art of minimally
invasive continuous glucose monitoring is based on the
enzymatic catalysis principle [1]. This approach still requires a
thin needle to be inserted subcutaneously which also involves
puncturing the skin. In addition, there have been several
noninvasive techniques which have been reported in the
literature. Solianis Monitoring has recently introduced a
prototype for a genuine noninvasive monitor of glucose level
using dielectric and optical spectroscopy sensors [2]. Data
collected from 150 channels are combined to estimate the
glucose level using some mathematical algorithm. Many other
techniques have also been published including breath signal,
electrical impedance, Ultrasound, NIR spectroscopy,
photoacoustic spectroscopy, and thermal spectroscopy [3-5].
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Most of these techniques are described in a very
comprehensive review article by Vashist [5]. Despite the
reported success of these methods under controlled conditions,
none seem to meet the required standards of accuracy and
safety when used in normal varying environmental conditions
such as physical movement and temperature variations. In this
research work, we report our preliminary attempts in using
nuclear magnetic resonance principle for the noninvasive
measurement of blood glucose level in humans. The presented
method and results are at the early stage of development. The
remaining sections of the paper are organized as follows: in
section II, the proposed methodology is introduced followed
by results in section III. This is then followed in section IV by
conclusions.
II. METHODOLOGY
A. Nuclear Magnetic Resonance (NMR)
Nuclear Magnetic Resonance takes place when a nucleus
in a magnetic field absorbs and emits electromagnetic
radiation at a specific frequency, called the resonant
frequency. In fact, for the emission of electromagnetic energy
to take place, the frequency and the magnitude of the magnetic
field are required to be at a certain proportion. This
phenomenon is called the Larmor precession which is
expressed mathematically as . The gamma in this
equation is known as the gyromagnetic ratio which is an
intrinsic and characteristic feature of the material. Each
element has a specific gyromagnetic ratio at which resonance
occurs, and this ratio is based on the nature of the material
itself such as magnetic moment and electron spins [6]. This
physical principle of NMR is used in many applications, such
as magnetic resonance imaging (MRI), magnetometers, and
NMR spectroscopy. NMR Spectroscopy is a technique used to
study the nature of material in a sample. Due to the extremely
small size of molecules, researchers cannot directly view them
and therefore depend on more advanced techniques of
detecting material through their interaction with other forms of
energy such as electromagnetic radiation. There are many
forms of spectroscopy, such as mass spectroscopy and infrared
spectroscopy. NMR technique takes advantage of the fact that
different elements have unique gammas (or set of gammas)
which can be employed to identify the nature of an unknown
substance using a known frequency and magnetic field [6].
This spectroscopic technique can therefore be carried out in
several ways. In one method, a constant frequency and
magnetic field can be applied to check whether or not the
particle resonates at the corresponding gamma. In another
method, one can sweep the magnetic field and keep the
frequency constant so that all the gammas that cause
resonance can be detected. NMR spectroscopy has
 Proceedings of the 8th IEEE GCC Conference and Exhibition, Muscat, Oman, 1-4 February, 2015
traditionally been used to study the structure and dynamics of
molecules. However, there have been some cases where the
technology has been used to study the concentration of
molecules. In one case, researchers used magnetic resonance
imaging units to detect the concentrations of iron in patients
suffering from iron-loading disorders such as
hemochromatosis and sickle cell disease [7]. This
measurement of iron concentration was done noninvasively.
This demonstrates the feasibility of using this technology for
not only measuring concentrations, but also for noninvasive
measurement. In another case, researchers used NMR
spectroscopy to measure the brain glucose concentrations [8]
and diabetes studies [9]. Therefore, it can be seen that the
technology seems to fit as an ideal solution to the problem of
noninvasive blood glucose measurement.
While it can be argued that the cost of NMR devices is
very high, it should be noted that there have been many
breakthroughs in the field of magnetic technology that signal a
decline in the price of future NMR devices. For instance, the
main reason that high resolution NMR devices are expensive
is that the devices use superconducting magnets which require
very low temperatures. Therefore, many NMR devices use
liquid nitrogen to cool the devices and keep them temperatures
between 63 and 77 Kelvin. Permanent magnets have not been
used because they do not provide enough magnetic field
intensity and also because they do not provide magnetic fields
that are homogenous. However, there have been
breakthroughs in permanent magnet technology that have not
only reduce the size of the magnet, but have also increased the
field intensity while still managing to maintain homogeneity
of the field. For example, a palm-size NMR, which uses
permanent magnets, has been introduced recently and it is able
to provide a homogenous field intensity of 0.7 Tesla [10, 11].
This is remarkable as NMR devices have traditionally been
very large. Also, by using permanent magnets, the cost of
NMR devices can be drastically reduced. Therefore, there is a
lot of potential for the development of a low cost NMR
devices in near future.
B. NMR Spectroscopy Systems
The NMR spectroscopy system that was primarily used in
this research was the Bruker Ultrashield NMR Avance 400.
This NMR system works by varying the frequency while
keeping the magnetic field constant. This produces a spectrum
that displays the frequency response of the material under
study. Therefore all the ratios that cause resonance can be
determined from the peaks of the spectrum. The maximum
frequency of the device is 400 MHz with magnetic field of
9.39 Tesla. glucose and other element in blood resonate at
similar frequency ranges. The system can be modeled as a
cascaded system where the output signal in the time domain is
the convolution of the input impulse and the different
resonance signals emitted by each constituent in the sample as
depicted in Fig. 1. This can be modeled as follow:
(1)
In the case of a sample which contains a mixture of blood
cells, hemoglobin, glucose, the output signal is:
(2)
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Where OB(t) is the convolution of all other components in the
blood. Using the convolution theorem, we can also express the
output signal in frequency domain as:
(3)
Fig. 1: NMR System with Blood Sample Model
Assuming that we have the spectrum of a calibration sample
of pure glucose solution with a known concentration, then we
can use equation (3) to compute the spectrum OB f . This
spectrum will then be used in equation (3) to compute the
glucose spectrum for an unknown glucose concentration in a
blood sample:
(4)
Fig. 2 shows a typical NMR blood spectrum with glucose
concentration of 100mg/dL. Notice that the y-axis is in
relative magnetic field intensity, and the frequency x-axis is in
Hz. The NMR system plots from left to right and therefore to
preserve the same spectrum, the axis was plotted in reverse in
MATLAB (Hence it appears to be ‘negative’, but this is just
for plotting purposes).
4
x 10 Spectrum of Blood and Glucose (concentration 100 mg/dL)
6.5
6
5.5
Relative Magnetic Field Intensity
5
4.5
4
3.5
3
2.5
2
1.5
-1800 -1600 -1400 -1200 -1000 -800
Frequency (-Hz)
-600 -400 -200 0
Fig. 2: A Typical NMR Blood Spectrum
The system was first tested by observing how much blood it
would take to mask the glucose spectrum. Therefore, to know
the approximate ratio of blood to mix with glucose solution, a
preliminary test was conducted to see the extent of the
distortion caused by the blood signal. The test samples were:
• pure glucose solution (450μL)
• glucose solution (449μL) with 1μL of blood
• glucose solution (440μL) with 10μL of blood
• glucose solution (400μL) with 50μL of blood
According to the experimental protocol approved by the
university IRB committee, the participating subject must first
sign the consent form. All blood samples were taken at the
university health clinic with the help of trained professionals
while observing the regulations. The blood had a glucose level
of approximately 94 mg/dL when it was taken. The NMR
 Proceedings of the 8th IEEE GCC Conference and Exhibition, Muscat, Oman, 1-4 February, 2015
spectra were then obtained as shown (zoomed in on the elements to calculate the ratio. The ratio for all samples was
glucose region) in Fig. 3. Results show that the blood was not calculated using the same procedure described in Fig. 4.
severely masking the glucose signal even when 50μL of blood
was added to 400μL pure glucose solution. This test was
beneficial because it showed the scope of how much blood
should be added for the other tests. It also shed some light on
the behavior of NMR signals when the volume of blood was
altered.
100 mg/dL Glucose Solution with Added Blood

Control
20000 1uL added blood
10uL added blood
50uL added blood
Relative Magnetic Field Intensity

15000

10000

5000

-1500 -1450 -1400 -1350 -1300 -1250

Frequency (-Hz)

Fig. 3: Results of First Set of Samples

C. System Calibration
The NMR introduces some fluctuations and random error
to every sample, therefore simply taking the amplitude does not
represent the concentration. One possible solution is to
compare the ratio of spectrum area occupied by the glucose to
that of blood, i.e:
A C
(5) Fig. 4: The Algorithm Block Diagram
A C

Simpson's rule was used to calculate the area. The glucose It was observed that the ratios were increasing as expected
concentration in the human subject's blood was naturally with glucose concentration since the other elements are
increased by asking the subject to take honey. For calibration relatively constant in comparison to glucose. These calculated
purposes, the glucose concentration of the subject was ratios are plotted in the calibration curve depicted in Fig. 5. As
measured using the standard glucose meter available at the can be seen, the linearity coefficient of determination, R2 is
clinic. The glucose concentration of this young university 0.96. This calibration curve will then be used to calculate the
student subject was measured at different times after taking unknown concentration of a glucose sample.
honey and found to be 120mg/dL, 100mg/dL, 95mg/dL and
92mg/dL. The blood samples were processed in the NMR
machine along with one pure reference glucose sample that had Test 1 Calibration Curve
a concentration of 100 mg/dL. Then, the following procedure 500
obtained values

was implemented using Matlab. The glucose-only sample was 400 y = 6.38x - 312.44
set as a reference, followed by scaling accomplished by
300 R² = 0.96
multiplying the glucose 100 mg/dL reference with the ratio of
the sample under test to the first sample. This way the error of 200
the NMR will also apply to the reference which eventually 100
made our calibration curve time and subject independent.
Then the areas of the glucose and blood sample spectra are 0
calculated. This is followed by dividing the reference glucose 0 50 100 150
spectrum by that of the sample under test. The result is the
spectrum that represents the concentration of other elements in glucose concentration (mg/dL)
blood. The area of spectrum of other elements is measured. Fig. 5: Calibration Curve
Finally the area of glucose will be divided by that of the other

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 Proceedings of the 8th IEEE GCC Conference and Exhibition, Muscat, Oman, 1-4 February, 2015
This algorithm was then applied on a sample taken from the
same subject with 92mg/dL. The calculated concentration was
found to be 89.12mg/dL with 3.13% error. This result was
encouraging which prompted us to conduct more tests on
another subject.
III. RESULTS
The algorithm described above was further tested on
another human subject. Calibration was conducted using
samples with concentrations 85, 108, 123, 137, and 163 mg/dL
as measured using the glucose meter available in the
university clinic. Fig. 6 shows the calibration curve for this
new subject.
Test 2 Calibration Curve
600
obtained values
400
200
0 during their own time.
0 50 100 150
glucose concentration (mg/dL)
Fig. 6: Calibration Curve of subject 2
The glucose concentration was tested on this subject 7 days
later. The glucose concentration of the new sample is
71mg/dL as measured by the glucose meter and was found to
be 62mg/dL as measured using our proposed NMR method
with 14.1% error. The linearity and sensitivity were lower in
comparison to the previous test. This is mainly because of
human and experimental errors. The glucose concentration of
the blood could change in the time between taking the
measurement and obtaining the blood samples and the
invasive glucose meter had ±5 level of uncertainty. The curve
obtained from this procedure was close to the previous
procedure if the errors were neglected. Hence the calibration
curve could be universal because this was done on a different
subject. Using these algorithms the concentration of the added
sample was calculated but with an error; given that this sample
was taken from the same subject a week later. Again the error
is due to random and instrumental errors.
IV. CONCLUSIONS
The proposed NMR method shows to be a promising
technique for measuring glucose in the blood. The other
elements in blood do not mask the whole spectrum and,
because NMR represent blood as a cascaded system of
different elements; glucose can be filtered by dividing the
output with the other elements. The NMR introduces a random
error for every test but this can be cancelled by comparing the
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areas within the same sample; hence, the glucose spectrum
area was compared with the other elements spectrum area and
the ratio of the areas equal the ratio of concentration.
According to the initial test it was seen that the other elements
have relatively constant concentration in comparison to
glucose which changes much more rapidly. Finally, each set of
samples had a different calibration curve but this problem was
fixed by scaling the reference glucose spectrum which made
all the sets fit on one global calibration curve that is subject
and time independent. There are still some errors which are
mainly due to random experimental errors such as uncertainty
of ±5 and small alterations in the intervals that were used to
compute the areas. More tests need to be carried out in order
to improve calibration curve and the results.
ACKNOWLEDGEMENT
Our team would like to thank everyone who contributed and
helped with this research work. Special thanks to the Lab
instructors and Health Center at the American University of
Sharjah for allowing the team to oversee the experiments
200
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