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Design of a Pulse Oximeter for Use in Mice Sponsor: Dr. Herbert H. Lipowsky Daniel J. Ford Deanna R. Nachreiner Robert E. Thomas Department of Bioengineering

Design of a Pulse Oximeter for Use in Mice

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Page 1: Design of a Pulse Oximeter for Use in Mice

Design of a Pulse Oximeter for Use in MiceSponsor: Dr. Herbert H. Lipowsky

Daniel J. FordDeanna R. NachreinerRobert E. Thomas

Department of Bioengineering

Page 2: Design of a Pulse Oximeter for Use in Mice

Pulse OximetryUsed to measure hemoglobin oxygen saturation levels quickly and non-invasively

Employs Light Emitting Diodes (LEDs) and Photo Detectors

Red ~ 600-750 nmInfared ~ 940 nm

Page 3: Design of a Pulse Oximeter for Use in Mice

Motivation

Animal studies using mice require blood oxygenation monitoringPulse oximetry currently works well in other small animals such as rats and rabbitsProblems in mice:

Small size & lack of available vascularizationFast heart rate (500-700 bmp)

Page 4: Design of a Pulse Oximeter for Use in Mice

Design CriteriaEffective

Economical

Probe dimensions: 1.5 cm x 1.5 cm

High sampling rate

High amplification

Low signal to noise ratio

Page 5: Design of a Pulse Oximeter for Use in Mice

Initial Approaches:Biopac System & Probe Reverse Engineering

Biopac System: modify parameters of an existing physiological monitoring system for use in mice

PROBLEMS: software and probe acquisition too expensive

SurgiVet Probe: obtain a functional pulse oximeter sensor, resolve pin configuration and detect signal via amplification circuit and oscilloscope monitoring.

PROBLEMS: device sophistication prevented adequate noise removal and amplification of signal

V3087 Mini Clip Sensor

Page 6: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Excitation Circuit

Constructed Sensor

Amplification Circuit

Oscilloscope

Oscilloscope

Computer

Design Flowchart

Verify Signal

Analog to Digital

Conversion

Data Analysis & Evaluation

Probe and Circuit Construction

Page 7: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Probe Construction

Red & Infrared LEDs

Red & Infrared Photodiodes

Plastic ClipCompleted Sensor

Page 8: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Circuit Construction1. LED Excitation Circuit

2. Transimpedance Amplification Circuit

Page 9: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Circuit Construction

Protoboard Wire-wrapped Circuit Board

Page 10: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Oscilloscope Verification

Signal from Red Diode

Signal from IR Diode

Page 11: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Oscilloscope Verification

Vmax Red

Vmax Infrared

Vmin Red

Vmin Infrared

Page 12: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Data Acquisition

Voltage Output from Red Photodiode

5.4

5.41

5.42

5.43

5.44

5.45

5.46

5.47

5.48

5.49

5.5

-2.5 -2 -1.5 -1 -0.5 0 0.5 1 1.5

Time

Volta

ge (V

)

CHAN1

Voltage Output from Infrared Photodiode

2.205

2.21

2.215

2.22

2.225

2.23

2.235

2.24

-3 -2 -1 0 1 2

Time

Volta

ge (V

)

CHAN2

Voltage Output from Red and Infrared Signals

Diastole = Maximum Output & Systole = Minimum Output

Page 13: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Data AcquisitionVoltage Output from Both Photodiodes

2

2.5

3

3.5

4

4.5

5

5.5

-3 -2 -1 0 1 2

Time

Volta

ge (V

)

RedInfrared

Page 14: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Data Analysis

Beer’s Law: I=Ioe-αcl

R = ln(IMaxRed/IMinRed)

ln(IMaxIR/IMinIR)

SpO2 = R*Ext(Hb IR) - Ext(Hb Red)

R*Ext(Hb IR)- R*Ext(HbO2 IR) + Ext(HbO2 Red) - Ext(Hb Red)

Page 15: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Design CalibrationVo vs. Thickness

LOG FITRed Photodiode

y = 7.6143e-0.1473x

0

2

4

6

8

10

12

14

16

0 5 10 15 20 25

Thickness (# sheets of paper)

Vo

(V)

Vo vs. ThicknessLOG FIT

Infrared Photodiode

y = 12.394e-0.21x

0

2

4

6

8

10

12

14

0 5 10 15 20 25

Thickness (# sheets of paper)

Vo (V

)

FIT: Vo=7.6143e-.1473t FIT: Vo=12.394e-.21t

Beer’s Law: I=Ioe-αcl

Proves that our device works under Beer’s Law, where l=t and Vo≈I

Page 16: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Data Analysis

R = ln(IMaxRed/IMinRed)

ln(IMaxIR/IMinIR)

SpO2 = R*Ext(Hb IR) - Ext(Hb Red)

R*Ext(Hb IR)- R*Ext(HbO2 IR) + Ext(HbO2 Red) - Ext(Hb Red)

Data Analysis: Calculation of Oxygen Saturation from Voltage Output

TRIAL Vmax RED Vmin RED Vmax IR Vmin IR R SpO2

1 9.314 9.27815 5.003175 4.998488 4.11469184 0.71857286

2 9.42933 9.3487 5.21885 5.193225 1.74470432 0.8013729

3 9.49933 9.43683 5.261975 5.253225 3.96642333 0.72572573

4 10.16938 10.09 5.79815 5.768775 1.54285914 0.80622833

5 10.20938 10.15938 5.840025 5.832525 3.82041644 0.73242284

6 10.4107 10.33883 6.01835 5.995 1.78204151 0.80044796

7 10.7962 10.7262 6.15755 6.140675 2.37032148 0.78464748

8 10.95948 10.883223 6.265075 6.24445 2.11749098 0.79173471

9 5.2234 5.128088 1.9704 1.934463 1.00048088 0.81817188

Page 17: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Design Verification

Photodiode Monitoring Experimentation

Experiment Result

LED Configuration Photodiode Response

RED IR RED IR

ON ON PULSE PULSE

OFF OFF NONE NONE

ON OFF PULSE NONE

OFF ON NONE PULSE0.00390.0288St Dev0.98560.9834Average

0.9815730.975532F

0.9827050.971498E

0.9865660.953413D

0.9922180.96161C

0.9833741.019548B

0.9872411.018983A

InfraredRedTrialRatio Max/Min

Proof of Consistency

Proves that each photodiode is successful in monitoring the appropriate

light signal while rejecting the other

Proves that regardless of output magnitude, the ratio of maximum to

minimum values are very similar

Page 18: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Calibration and Verification

Oxygen Saturation vs. Timewith Breath Held y = -0.0172x + 81.947

R2 = 0.6684

80

80.5

81

81.5

82

82.5

0 20 40 60 80 100

Time (s)

SpO

2 (%

)

SpO2 %Linear (SpO2 %)

Proves that our device successfully detects changes in blood oxygen saturation levels

Here one sees decreased saturation as time without oxygen increases

Page 19: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Data Interpretation

•Observed values of oxygen saturation that were significantly lower than expected for healthy subjects

•The device was tested and is consistent in measuring changes in oxygen saturation levels

•The final step in developing commercially-available pulse oximeters is an aggressive calibration technique involving real-time measurements of blood oxygen partial pressures using blood gas analysis

•Possible sources of error in data analysis:

•Scope variance

•Motion artifacts

•Inconsistencies in probe placement

Page 20: Design of a Pulse Oximeter for Use in Mice

Final Design Approach:Comprehensive Probe and Circuit Construction

Animal Testing

•Animal testing on was performed in Centralized Biological Laboratory

•Mouse was placed under general anesthesia

•Probe was placed on mouse thigh

•Signal was observed

•Data was unable to be acquired

Page 21: Design of a Pulse Oximeter for Use in Mice

Design CriteriaEffective

Economical

Probe dimensions: 1.5 cm x 1.5 cm

High sampling rate

High amplification

Low signal to noise ratio

Page 22: Design of a Pulse Oximeter for Use in Mice

Deliverable… a device which:

Detects changes in hemoglobin light absorbance based on oxygen saturation levels in humans and mice

Detects changes in SaO2 levels in humans

Page 23: Design of a Pulse Oximeter for Use in Mice

Budget: All Design ApproachesFinal Budget

Equipment # Price Equipment # Price

SurgiVet Probe 1 $0.00 LED Holders 8 $2.58

OPA 380 4 $15.80 IR Photodiode 2 $0.00

OPA 343 4 $5.16 Red Photodiode 4 $0.00

OPA 350 5 $6.50 Project Box 1 $6.99

Red LED 4 $2.98 Banana Plugs 4 $5.18

Infrared LED 2 $2.98 Circuit Board 1 $0.00

TOTAL EXPENDITURE: $48.17

Conclusion: Operated within our means; definitely succeeded in producing an economic solution, as pulse oximeter systems are priced at upwards of thousands of dollars

Page 24: Design of a Pulse Oximeter for Use in Mice

Task January February March April

Wk1 Wk2 Wk3 Wk4 Wk1 Wk2 Wk3 Wk4 Wk1 Wk2 Wk3 Wk4 Wk1 Wk2 Wk3 Wk4

Idea Generation& Research

Meet with sponsor

Generate ideas

Research Sensors

Sensor Design

Determine Pin Configuration

Research Sample Rates

Material Ordering

Circuit Construction

Design Amplification Circuit

Construct Circuit to Oscilliscope

Construct Circuit to A/D Converter

Testing & Improvement

Contact Vet/ Obtain Mice

Detect Signal from Humans and Mice

Design Computation of Oxygen Saturation

Final Report

Prepare & Give Final Presentation

We successfully completed our objectives in time,

however with more time, a more accurate device could

have been designed

Page 25: Design of a Pulse Oximeter for Use in Mice

Future Directions

Complete further animal experimentation, including data acquisition and processingProgram code to acquire and process data in real-timeAttempt to remove motion artifactPerform blood-gas calibration to obtain accurate values

Page 26: Design of a Pulse Oximeter for Use in Mice

Acknowledgements

Dr. Herbert Lipowsky

Dr. Roger Gaumond

Dr. Nadine Smith

Dr. Kathleen Heiderstadt

Gene Gerber

Wade Reeser

Page 27: Design of a Pulse Oximeter for Use in Mice

Questions?