OPTICAL MEASUREMENT OF GLUCOSE CONCENTRATIONS
USING RAMAN SPECTROSCOPY
Michael J. Vilaboy', Aysegul Ergin2,Alain Tchouassi3,Richard G r e e d , Gordon A. Thomas2.
'Department of Electrical Engineering, New Jersey Institute of Technology, Newark, NJ
2
Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ
3Depar!mentof Physics, New Jersey Institute of Technology, Newark, NJ
AbstraceTbe need for devising a method to noninvasively
measure the glucose concentration in the body is great because
ofthe application to improving blood sugar control in diabetics
as to improve the quality and longevity of life. The noninvasive
method studied in this paper is to use an optical measurement
ofa glucose solution to predict the actual glucose concentration
of that solution by means of spontaneous Raman Spectroscopy
using multivariate regression analysis. Although t h i method
has been studied by many groups of researchers, the advantage
comes with a small, compact, relatively inexpensive, and low
intensity system that could be more easily implemented into a
practical device that could be used for clinical and patient self
monitoring. These advantages over previous studies include
reduced incident laser power, at 60mW, and reduced
integration times, with a significant signal to noise ratio at
physiological concentrations. The resultx ofthe study showed a
significant correlation between the predictor variable, optical
measure of glucose concentration, to the outcome variable,
actual glncose concentration, with a correlation coefficient of
0.9998'7, an F(2.2) statistic of 7599, and a p-value of lY"'04.
I. INTRODUCTION
There exists a great need to provide people who suffer
kom Type I and Type II Diabetes a device that can
accurately and noninvasively measure the blood sugar
content-in the body. Recent studies have suggested tbat
using optical techniques to measure the blood-glucose level
in the body are very promisiig [l-51. One p u p of
researchers have done experiments using Raman
Spectroscopy to measure the glucose concentration in blood
plasma [2], while others have investigated the feasibility of
using Raman Spectroscopy to measure the glucose
concentration through the Aqueous Humor of the eye, which
lies between the cornea and the lens [3-51. The advantage in
measuring the glucose though the Aqueous Humor is that
far less constituents are present in the eye that would
interfere with the spectroscopic detection of glucose, while
the primary concern is incident laser power. It is then the
focus of this study to provide evidence of the feasibility of
such a measurement, while still using a small, compact,
relatively inexpensive, and low intensity system that could
be more easily implemented into a practical device.
In simple terms, Raman Spectroscopy is a method to
efficiently collect the Raman scattering produced by an
incident source, in which the source photons collide with the
molecules, force those molecules to vibrate, and then those
molecules reemit its vibrations in the form of light. A
sample Raman spectrum of water and a glucose solution
with the selected peaks for analysis is shown in Figure 1
plotted as Raman intensity in A D counts vs. Raman shift in
inverse centimeters kom the 830-nm excitation wavelength.
As seen, the water spectrum has a broad background that
has the form of an exponential decay function, whereas, the
0-7803-7767-2/03/$17.0002003 IEEE
glucose spechum has the same background with several
peaks riding on top of that background. The two peaks that
were selected as to analyze the correlation between the
optical measure of the glucose solution and its
corresponding concentration are at 1065 and 1126 cm",
respectively. These peaks were chosen due to their relative
size to the background and because of their location relative
to the large background.
4 c c Q q . , . , . , . , . ,
li FI
b m e n shl[ cni' 1
Fig. 1. Sample b"spectra of Gluso~cSolution and Watcr with
Idcntifcation of Selected Raman Peaks
II. METHODOLOGY
The apparatus consisted of an 830-nm diode laser with a
power output of 6 h W , a 5 an-'resolution spectrometer
with an electronidly cooled CCD row detector, an
Inphotonics Raman probe, and an alumhum mirror in
which a drop of the sample was placed The probe has an
excitation fiber from the laser, and a collection fiber to the
spectrometer in which the excitation and collection path
share the Same lens for optimal signal to noise. The use of
this system is advantage& because of its compactness and
relatively inexpensiveness. Unlike other CCD detectors
using Liquid Nitrogen to cool them, this one incorporates an
electronically cooled detector to reduce noise, but is
relatively inexpensive and easy to use.
In this study, five concenhtions (5%, 1%, 0.5%, 0.25%,
and 0.1%, .where % = g/lOOmL) were selected as to
determine the correlation between the predictor and
outcome variables. The data tbat was collected for each
concentration consisted of 10 measurements with an
integration time of 60s each. The data was then analyzed by
performing a 21 point Savitzky-Ciolay smoothing on each
measurement, an average of those measurements, and
finally a fitting in the selected region using a nonlinear least
squares fitting procedure BS to increase the Signal to Noise
329
 Ratio (SNR). The fitting model used is shown in Equation 1,
which consisted of the sum of two Lorentzian modeled
peaks, an exponential background, and a coostant term.
where A, is the area under the impeak, w, is the width of the
i* peak, x, is the location of the im peak, & is the
magnitude of the exponential background, T- is time
constant of the exponential background, and yo is the
constant term. The Raman Spectrum of 0.1% Glucose
solution in the selected region, a h r performins the
smoothing and averaging analysis with the nonlinear least
squares fit as specified by Equation 1, is shown in Figure 2.
1W 109 +loo 1130
RamnSMIIm? 1
Fig. 2. (0) PlotofRawdstaafkrprcpmassingwi"onlincarLeasl
SquarcsFiaingofspccificdmodslb 0.1%Glucosc,N = 10,t=M)s: (5)
Plot of Individual and Collective Lorrntdan P& BS Fitted by Nwlincar
LeaslSquaraFittospcc~cdmodclfor0.I%Glucosc,N=10,t=Mk.
As indicatd in Figure 2% the data was fitted with the model
in Equation 1, and the exponential background was
extracted In Figure 2b, the exponential back&ound was
then sub- and the individual fits for each of the peaks
were plotted. The fit parameters, more specifically, the area
under the respective peaks, were then extracted to use in a
multivariate regression analysis as to determhe the
correlation between the actual glucose concentration and its
optical measure by means ofRaman Spectroscopy.
m.RESULTS
.. ~ n e results of the study show a significant correlation^
b e t w e the predictor variable, that is, the area under the
selected Ramau peaks of Glucose, to the outcome variable,
the actual concentration of the Glucose solution with a
comlation coefficient of 0.99987, an F(22) Statistic of
7599, and a pvalue of 1.3*104. The predicted concentration
Was then d d a t e d and compared to the actual
concentration as shown in Figure 3, with 5% error bars. The
standard deviation of residuals for the predicted vs. actual
concentration plot was 0.0236% or 23.6mg/lOGmL.
' 1
b
0
O
.'
r'
I 2 3 4 5
1
Achlal Concentration [ g/100mL 1
Fig. 3. Rsdictcd Concsntration vs. A d Conantration with 5% m r
bars
N.DISCUSSION
Although this correlation has been studied in the past by
various groups, including Lambert et al and Tarr et al, the
advantage is that the device and method currently being
used is a small, compact, relatively inexpensive, and low
intensity system opposed to the extremely large, more
expensive setups that have intense excitation sowces, liquid
nitrogen cooled detectors, and/or integrate for long periods
of time. These advantages over previous studies include
reduced incident laser power, at 6OmW and reduced
1200
integration times, with a significant signal to noise ratio at
physiological concentrations as to measure the
Concentration accurately. The significance of this research is
then more easily realiible in that it can be conceived that a
'system similar to the one-beingused could be more easily
implemented into a practical device that could be used for
clinical and patient selfmonitoring.
ACKNOWLEDOMENTS
This work was funded by the Gustavus and Louise
Pfeiffer Research Foundation. We 'thank Dr. Robelt
Fechber of the University of Medicine and
Dentistty of New Jersey for providing the samples.
REFIBENCES
[l] G. Cot6-"Noninvasivc and Minhaally-Invasive Optical Monitoring
Tedulologics." American Soeiery for Numitiom/ Sciences, vol. 131, pp.
1596S-I604S,2001.
[2]T.Koo, A. Bcrgn, I. Ibhm, and M. Fe14 "Me~~ursmnu of Glumsc in
Humao Blood Scrum using Raman Spdmswpy,"IEEE LEOSNwusletter,
vol. 12(2), pp. 18-19.April 1998.
p] J. Lambert, M Stomc-Lombsrdie, and M Borckt, "Measurement of
Physiologic Glumsc Levels Using Raman Spectroscopy m a Rabbit
Aqusous Humor Model," IEEE LEOS Newsletter, vol. 12(2), pp. 19-22.
April 1998.
[4]R Tm, and P. Stef€cs,"Ibc Non-InvasiveMcawrc of DGlueo~em
the Ocular Aqueous Humor using Stimulated Ramaa Spedmswpy,"IEEE
LEOSNewdetter, vol. 12(2), pp. 22-27,April 1998.
[SI P. Steffss,"M-Bascd Mearursknls of Glucore in the Ocular
Aqwus Humor: an Efficacious P o d for D c t c ~ o nof S m
Gluwsc Lcvcls," Dinbetes Technolozv & Iherapeulics,vol. 1(2), pp. 12%
133,1999.
33IO