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THE NOVAMOUSETM
PULSE OXIMETER
SHERAZAD MAHOMEDALLY,
NICOLE SERAGO, AND POOJA SHAHDEPARTMENT OF BIOMEDICAL ENGINEERING
VANDERBILT UNIVERSITY SCHOOL OF ENGINEERING
APRIL 22, 2003
ADVISORS: BOB ALLEN & BEN SCHNITZMICRONOVA TECHNOLOGY
INSTRUCTOR: DR. PAUL KINGASSOCIATE PROFESSOR OF BIOMEDICAL AND MECHANICAL
ENGINEERINGVANDERBILT UNIVERSITY SCHOOL OF ENGINEERING
TABLE OF CONTENTS
1. ABSTRACT…………………………………………………………………………....
2. INTRODUCTION
2.1. SIGNIFICANCE OF MICE……….…….……………………………...………..
2.2. MARKET POTENTIAL…...……………………………………………...………
2.3. PULSE OXIMETRY...…………………………………………….………………
2.4. PROBLEM TO BE SOLVED……………………………………………………..
2.5. GOALS…………………………………………………………………………….
2.6. CURRENT DEVICES…………………………………………………………….
3. METHODOLOGY
3.1. PULSE OXIMETRY THEORY…..………………………………………………
3.2. RATIO OF RATIOS………………………………………………………………
3.3. PROJECT SCOPE AND CIRCUITRY…………………………………………..
3.4. DESIGN SPECIFICATIONS………....………………………………………….
4. RESULTS
4.1. EXPERIMENTAL DESIGN………………………………………….………….
4.2. DESIGN PERFORMANCE……….…………………………………….……….
4.3. PROBLEMS ENCOUNTERED/SOLUTIONS………………………….……….
4.4. SAFETY ANALYSIS……………………………………………………..………
4.5. ECONOMIC ANALYSIS…………………………………………………………
5. CONCLUSIONS…………………………………………………………….…………
6. RECOMMENDATIONS………………………………………………….…………..
7. REFERENCES…………………………………………………………...……………
APPENDIX*
A. INNOVATION WORKBENCH…………..………………………………………
B. DESIGNSAFE REPORT…………………………………………………...…….
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1. ABSTRACT
This design project is the creation of the NovaMouseTM pulse oximeter, which will
be used to measure oxygen saturation and blood pressure of mice. The measurement of
the oxygen saturation level is important because an insufficient supply of oxygen can
result in death within minutes during surgery. The miniature size of mice that allow for
ease of maintenance is also what causes the largest drawback during research involving
mice. The main goal of this project is to build a pulse oximeter that is small, has the
capability to be wireless in the future, and can reach heart rates up to 800 beats per
minute. One photo sensor is used for all measurements because the two light-emitting
diodes are pulsed at different intervals. The received red and infrared signals have a non-
linear relationship and are then mathematically preprocessed and normalized so that a
ratio of the two can theoretically be a function of only the concentration of
oxyhemoglobin and reduced hemoglobin in the arterial blood. This concentration ratio
known as the ratio of ratios (R) should be constant since oxygen saturation is essentially
constant for measurements taken over such a short period of time. The circuit designed
has a frequency range of 0.1 hertz to 250 hertz and a gain of 625. From the Bode plots,
the lower cutoff for the infrared light-emitting diode is not seen. The Bode plot of the red
light-emitting diode illustrates the stair step characteristic of a Butterworth filter. These
results are seen because the bandwidth is so small (only two magnitudes). The circuit is
ready to be miniaturized and tested on mice.
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2. INTRODUCTION
2.1 SIGNIFICANCE OF MICE
The field of biomedical research on mice is rapidly growing. The popularity of
mice in research is increasing due to their ease and quickness of breeding, the ability to
breed transgenic mice, and their miniature size, which reduces their maintenance costs in
laboratories. This design project is the creation of the NovaMouseTM pulse oximeter,
which will be used to measure oxygen saturation and blood pressure of mice.
2.2 MARKET POTENTIAL
NovaMouseTM will be marketed to universities and hospitals nationwide to aid in
research and data acquisition. Approximately 50,000 devices are projected to be sold in
2004 with one million mice as potential targets. This accounts for around 10-20% of the
market share. It is difficult to pin down the exact market since the FDA and NIH do not
keep records on mice. [1]
2.3 PULSE OXIMETRY
Pulse oximetry is used to measure blood oxygen saturation. Heart rate is also
easily attainable using a pulse oximeter. The measurement of the oxygen saturation level
is important because an insufficient supply of oxygen can result in death within minutes
during surgery. Also, pulse oximetry is very important in Intensive Care post-surgery to
monitor recovery. Pulse oximetry readings are standard measurements in human and
veterinary surgical monitoring. This shows that there is a need for such measurements in
surgical procedures on mice.
These measurements would also be useful for research on free ranging mice. For
example, oxygen saturation measurements could be used on researching the effects of
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alcohol and carbon monoxide poisoning as well as comparing cardiac output to oxygen
saturation. [2] The additional heart rate measurements would also be useful in such
studies. An example of the need for this measurement can be found here at Vanderbilt.
At the Vanderbilt Medical Center, Dr. Timothy Blackwell, M.D. would like a pulse
oximeter to use on the mice in his investigation of pulmonary fibrosis. [3] Fibrosis, or
scarring of the lung tissue, results in permanent loss of the tissue’s ability to transport
oxygen. A pulse oximetry measurement would show decreased oxygen saturation if
fibrosis was present. [4]
2.4 PROBLEM TO BE SOLVED
The miniature size of mice that allow for ease of maintenance is also what causes
the largest drawback of research involving mice. Conventional methods for obtaining
physiological measurements, such as blood gases and heart rate, do not work on mice.
The NovaMouseTM pulse oximeter is a device to accurately measure blood oxygen
saturation and heart rate in mice.
Prior to this product, any time data acquisition of pulse oximetry was desired, a
mouse was killed in the process since the only way to acquire that data was via sticking
rods through the mouse’s hands and feet. This device will spare the mouse’s life allowing
for the observance of several drug administrations and the reusing of mice.
NovaMouseTM would allow for reduction of costs. Not only would the device itself be
less expensive than competitor’s products by a factor of ten, but the survival of the mice
would also allow for reuse of the expensive transgenic mice. [1]
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2.5 GOALS
The main goal of this project is to build a pulse oximeter for a mouse with the
following characteristics. First, the sensor must be small enough to accurately obtain
pulse oximetry measurements from the proximal end of the tail of a mouse as well as
monitor the heart rate of the mouse. Second, the pulse oximeter must be compatible so in
the future it can be wireless. This will help with ease of movement of the mouse during
studies that require measurements to be taken over extended periods of time in which the
mouse should be in its natural environment. Next, the pulse oximeter must be able to
accurately detect heart rates of up to 800 beats per minute. Also, the device will be
reusable and the packaging design will be built on a flexible substrate using chip and
wire. The sensor will have a cuff format that will be located in a hard to reach place so
that the mouse doesn't eat it off. The sensor will also be discrete, meaning that there
won't be any wires attached.
To achieve these goals, a variety of literature was used. An introduction to the
aim of the project and the probable components was attained through meetings with
MicroNova Technology staff, including Ben Schnitz and Bob Allen. Further research
was done through the use of biomedical handbooks, internet searches, and patent searches
to verify pulse oximetry designs and parameters. To determine the possible uses and a
definite market for the device, a personal interview was conducted with Dr. Blackwell.
Dr. Blackwell also was helpful in providing information about previous devices and their
downfalls. With this information, websites of individual companies, including Nonin
Medical, Inc. were searched.
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2.6 CURRENT DEVICES
Recent devices do not allow for movement of the mouse and are incapable of
detecting heart rates high enough to monitor that of mice. One example is a pulse
oximeter designed by Nonin Medical, Inc. This
device, shown in Figure 1, only works on large
rodents and is not useful for a mouse. The Velcro is
flimsy and it is difficult to attach to the mouse. Also,
although this oximeter can read a human and large
rodent’s blood saturation, it cannot read a mouse’s due
to a heart rate of between 450 and 800 beats per
minute. Even though this device allows for some
movement of the mouse, the wires can still hinder normal behavior of a free ranging
mouse. On the other hand, NovaMouseTM will try to overcome all these disadvantages
posed by the Nonin device. [5]
3. METHODOLOGY
3.1 PULSE OXIMETRY THEORY
In order to design NovaMouseTM, it is important to look at the theory behind pulse
oximetry. The NovaMouseTM pulse oximeter works by measuring the hemoglobin in the
arteries found in the mouse’s tail via optical sensing. The device will be secured to the
proximal end of the tail where a central artery and two veins are found.
Relative proportions of oxygenated and reduced hemoglobin in the arterial blood
determine the oxygen saturation (SpO2) of arterial blood. Reduced hemoglobin is
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Figure 1: Nonin Pulse Oximeter
hemoglobin that is not carrying oxygen, i.e. deoxygenated blood, while oxyhemoglobin
corresponds to oxygenated blood. The pulse oximeter works by measuring the difference
in the absorption spectra of these two forms of hemoglobin in order to calculate the SpO2
using two light-emitting diodes, one of wavelength 700 nm in the red band and one of
wavelength 950nm in the infrared, and a photodiode. Similar to the human’s finger, the
light-emitting diodes are used to sense the degree of oxygen saturation in blood since the
reduced hemoglobin absorbs more light in the red band than does oxyhemoglobin, while
oxyhemoglobin absorbs more light in the infrared band than does reduced hemoglobin.
Because the tissue contains arterial, capillary and venous blood, as well as
muscle, connective tissue and bone, the red and infrared signals received from the probe
contain both a DC and a pulsatile component. While the large DC component is
influenced by the absorbency of the tissue, the intensity of the light source, and the
sensitivity of the detector, the small pulsatile component corresponds to the pulsatile
arterial blood.
3.2 RATIO OF RATIOS
The amount of light transmitted through the tail is measured several hundred
times per second at both wavelengths. One photo sensor is used for all measurements
because the two light-emitting diodes are pulsed at different intervals (6). The received
red and infrared signals have a non-linear relationship and are then mathematically
preprocessed and normalized so that a ratio of the two can theoretically be a function of
only the concentration of oxyhemoglobin and reduced hemoglobin in the arterial blood.
This concentration ratio known as the ratio of ratios (R) should be constant since oxygen
saturation is essentially constant for measurements taken over such a short period of time.
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The preprocessing MicroNova plans to do such as averaging over time and planting the
device on a relatively immobile area will eliminate extra noise variables such as motion
artifact and ambient light [7].
The mathematical side of the ratio of ratios includes Equation 1 that characterizes
( ∑ Hb( λ R) - ∑ Hb( λ IR) *R) 100 Equation 1∑ Hb(λR) - ∑ HbO2(λR) + [ ∑ HbO2(λIR) - ∑ Hb(λIR)] R
the amount of light absorption at each frequency for oxygenated and deoxygenated blood
to give the non-linear relationship referred to earlier. The values in Table 1 represent the
Table 1: Saturation of hemoglobin at both wavelengths.
∑ Hb(λR) 0.81∑ Hb(λIR) 0.18
∑ HbO2(λIR) 0.29∑ HbO2(λR) 0.08
saturation of hemoglobin at each wavelength. For instance, ∑ Hb(λIR) is the saturation of
deoxygenated blood at 950 nm. Using these values Equation 2 is generated and R, the
ratio of ratios, is used to get the oxygen saturation desired. R should be between .5 and
2.5 [1].
SpO2 = (.81-.18R) 100 Equation 2 (.29-.08R)
3.3 PROJECT SCOPE AND CIRCUITRY
Figure 1, which represents the project outline, illustrates our scope of the project
as the blue parts, while the red parts represent the parts MicroNova still has to do. The
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Biosensor
Preamp A/D Conv Transmitter Receiver D/A Conv SignalProcessing Data Acquisition
Figure 2: Project outline.
first part of the project to research and design is the biosensor. Here, the light-emitting
diodes sense the blood saturation and send both the DC and pulsatile signal to the
photodiode. In the preamplifier stage, the transimpedance amplifier converts the current
coming from the photodiode to a voltage. Because there is a very large input impedance
and negligible output impedance, a very large feedback resistor is used to set the current
gain as can be seen in Figure 2. Also included is a capacitor of .1 microfarad in order to
tune out high frequency measurements and stabilize voltage spikes. Once the signal is
conditioned into a voltage output, an analog to digital conversion card is used to format
the signal into a digital signal that can be sent wirelessly.
In order to wirelessly transfer the information serial transmission is utilized since
it requires only one transmitter. Moreover, it is accomplished using amplitude shift
keying modulation. This method is preferred to other types of modulation because 1) it is
the easiest to implement, 2) it is easy to read – does a signal exist or not, and 3) it does
not require any sort of interpretation of the signal.
Although the one drawback is that there can be lots of error since zero acts as a
data point, there are ways to fix the error. For one, there can be several check points
where one can check for 5 points before and after the point recorded to make sure the
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C5
2.72 nF
R5
V13.6 V
-InB
C4
1.5 nF
D3
Photo
R1100 K
C3
1 uF
+InA C62 nF+InA
OutA
OutB
D2
950 nm
V+
R6
R2
330 K
33 K
V-V-
R3a1 M
330 K
C1
0.1 uF
OutB
LT1490CN8-ND
+InB
R3
160 KLT1490CN8-ND OutA
-InB
V+D1
700 nm
-InA
+InB
C2100 pF
-InA
R4
330 K
Figure 3: Schematic of pulse oximeter using two dual op-amps.
signal received includes zeros that are part of the signal and not zeros that mean the
signal is dead. Although this decreases the sampling rate, that is acceptable because the
pulse oximeter for mice doesn’t need a high sampling rate. Another advantage is that the
distance between the mouse and receiver is short; thus there is less noise [2].
After the signal is received, it is reconstructed back into an analog signal and then
sent first through an active high pass filter of gain = 6.25 to get rid of signals below .1
Hertz and then a two-pole low pass filter (8) to rid signals above 250 Hertz. This gives
the desired frequency range of .1-250 Hertz. Finally, the signal is passed through yet
another low pass filter with a gain of 100 to get amplification and get rid of all
frequencies passed the highest, important frequency before data acquisition. If this anti-
aliasing process was not done, we would use the Nyquist theorem of sampling frequency
for biological situations and sample at a frequency of 5 times the highest frequency as
opposed to five times the highest, important frequency. Once the data is collected, the
signal is processed in LabView in order to monitor the blood saturation.
3.4 DESIGN SPECIFICATIONS
In order to be able to detect a high heart rate, the frequency range must be
between 0.1 Hertz and 250 Hertz. Therefore, the circuit must eliminate all frequencies
above and below this range including random noise. Also, power to the operational
amplifier and light-emitting diodes will be provided via inductive coupling and voltage
regulators. But right now, we are modeling the dual operational amplifiers with a power
supply of 3.6 volts. This type of operational amplifier can be operated with a power
supply from 2 volts to 44 volts. However, a voltage of 1.7 volts is needed for the light-
emitting diodes, so right now the function generator is being used as the source. Also
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there is a very large gain in the transimpedance amplifier with a gain of 625 in the active
filtration. As for the device, it will be designed to fit a mouse with the following
dimensions: 3 millimeter diameter at the base with 2 centimeters before the tail begins to
taper.
4. RESULTS
4.1 EXPERIMENTAL DESIGN
Figure 1 below shows the experimental setup for our pulse oximeter design. The
function generator provides the light-emitting diode with a voltage of 1.7 volts and the
power supply provides the circuit with a voltage of 3.6 volts. The light-emitting diode
and the photodiode are put in a box so that ambient light cannot affect the signal. The
function generator is set to a frequency of 0.1 hertz to begin with and is incremented all
the way to 250 hertz. The output signal is seen on the oscilloscope and the output voltage
is recorded.
4.2 DESIGN PERFORMANCE
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Figure 2: Experimental design setup.
Currently, the characterization of the light-emitting diodes has been completed. This
means that Bode plots have been obtained using the red and the infrared light-emitting
diodes by pulsing them from the frequency range as mentioned above. The results
obtained are shown in graphs 1 and 2 below. Looking at the graphs, it can be noted that
the since the bandwidth is very small, the plot appears as a stair step for the red light-
emitting diode.
Characterization of IR LED
0
50
100
150
200
250
0.1 1 10 100 1000
Frequency (Hz)
Volta
ge (m
V)
Characterization of Red LED
174176178
180182
184
186188
190
0.1 1 10 100 1000
Frequency (Hz)
Volta
ge (m
V)
Graph 1: Bode plot for red LED. Graph 2: Bode plot for infrared LED.
4.3 PROBLEMS ENCOUNTERED/SOLUTIONS
During this project several problems were encountered. First, the red light emitting
diode had a voltage range of 1.8 volts to 4 volts and the infrared light-emitting diode had
a voltage range of 1 volt to 1.5 volts. Since there was no overlap in the voltage range,
there was no way to power our light-emitting diodes. To solve this problem, light
emitting diodes with the same or overlapping voltage ranges were found at 1.7 volts.
Thus, a voltage divider will be used to make sure that the battery voltage does not go
below 1.7 volts; otherwise the light-emitting diodes will not work.
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Another problem was that several operational amplifiers stopped working due to
static electricity and therefore operational amplifiers had to be switched and static
wristbands were carefully used. The light-emitting diodes had inconsistent performance.
Sometimes they worked and other times they didn’t. Several different types of light-
emitting diodes were used. Similarly, there were problems with the filters. Several
different techniques of trouble shooting were used.
Finally, there were problems characterizing the circuit. The reason the Bode plot
appeared incorrect is because the frequency range is really small. Also, there was a need
to increase the gain in the circuit. This was accomplished simply by changing the
resistors in the low pass filter. Once these changes were made, it was easier to see an
output signal on the oscilloscope and get the Bode plots desired, shown above in graphs 1
and 2.
4.4 SAFETY ANALYSIS
Using the program Designsafe, we were able to perform a risk assessment on the
NovaMouseTM pulse oximeter design. From the analysis, we were able to conclude that
the severity of risk is minimal and the probability of danger is unlikely and negligible for
the most part. This program also helped us determine risk reduction methods for our
design including a manual for users, warning signs, and on-the-job training for the
operator.
4.5 ECONOMIC ANALYSIS
The development cost analysis for this project includes the cost of labor which
includes 150 hours for 3 students at $15/hour. This comes out to $6750, plus $100 for
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parts. There was no cost incurred for travel, technical services, legal fees, etc. Thus, the
final cost was $6850. There will be no FDA involvement since this device is used on
animals and there is no need for animal welfare considerations since the pulse oximeter is
just cuffed on the proximal end of the mouse’s tail and thus, is not invasive. Also, the
cost of maintenance is unknown but only includes the cost to maintain the receiver/power
supply if it breaks. The pulse oximeter cuff is reusable and will need no maintenance
since they are small and cheap and can be thrown away if broken. The cost of this device
will be in the hundreds which is less by a factor of ten from other current designs such as
Nonin Medical, Inc. MicroNova Technologies predicts $5-10 million dollars in sales for
the year 2004.
5. CONCLUSIONS
During the course of this project a lot of time was spent working on the
breadboard circuit prototype and troubleshooting. Since there were problems with the
parts, the focus was on rebuilding and testing the circuit. Research was completed on
pulse oximetry circuit design and different possible parts and different light-emitting
diodes and stages of the circuit were tested specifically to obtain readable signals. The
circuit was characterized to obtain Bode plots by changing the frequency range and gain
based upon updated schematics. DesignSafe and Innovation Workbench programs were
completed to analyze problems and risks associated with the device and the design
process.
From the Bode plots, the lower cutoff for the infrared light-emitting diode is not
seen. The Bode plot of the red light-emitting diode illustrates the stair step characteristic
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of a Butterworth filter. These results are seen because the bandwidth is so small (only
two magnitudes). The circuit is ready to be miniaturized and tested on mice.
6. RECOMMENDATIONS
From this point, the completion of the project will be done by Ben Schnitz and
future MicroNova Technology interns. The analog to digital conversion, wireless
transmittance, digital to analog conversion, and data acquisition stages need to be
designed and implemented. The circuit will then be miniaturized such that the biosensor
and transimpedance amplifier will fit in the cuff on the mouse’s tail. Testing will be done
to ensure the device works on mice. The successful device will eventually be sold to
interested customers.
Issues concerning ethics do not play a large role in this project. The
NovaMouseTM device does not in any way harm the mouse since it is noninvasive and
will be miniaturized so that it will not impair the mobility of the animal. The pulse
oximetry measurements do not have any negative effects on the quality of the life of the
mouse. Any harm to the mouse being used would be the result of whatever research is
being done on it, which is outside of the scope of this project.
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7. REFERENCES
1. Schnitz, Ben. MicroNova Technology, Inc. Personal interviews. October
2002-April 2003.
2. Diab, Mohamed K. “Signal Processing Apparatus.” United States Patent
5632272. 27 May 1997.
3. Blackwell, Timothy. Personal interview. 5 December 2002.
4. Facts About Pulmonary Fibrosis and Interstital Lung Disease. 9 April 2003.
http://www.lungsusa.org/diseases/pulmfibrosis.html
5. Nonin Medical, Inc. 6 December 2002. http://www.nonin.com
6. Webster, John G. Medical Instrumentation: Application and Design. New
York: John Wiley & Sons, Inc., 1998.
7. Mortz, Margaret S. “System for Pulse Oximetry SpO2 Determination.” United
States Patent 6385471. 7 May 2002.
8. Neamen, Donald A. Electronic Circuit Analysis and Design. Chicago: Irwin,
1996.
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