Chapter 9 Biomedical Sensors - melab.snu.ac.kr
Transcript of Chapter 9 Biomedical Sensors - melab.snu.ac.kr
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Chapter 9 Biomedical Sensors
Hee Chan Kim
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CHAPTER 9. Biomedical Sensors
9.1 Introduction
9.2 Biopotential Measurements
9.3 Physical Measurements
9.4 Blood Gases and pH Sensors
9.5 Bioanalytical Sensors
9.6 Optical Biosensors
In Vitro Diagnostics Technology
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지식과 수기
의사의 도구
의료기기의 정의
약 의료기기
생물학적제재
Medical Devices : the things that Biomedical
Engineers provide
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진료재료–의료소모품-의료비품-의료장비
8,264점 2,088억원
MRI,Monitor 등 16,603점 115억원
침대,냉장고 등
8,274점 39억원
각종수술기구, 램프,전극,센서 등
Varieties in Medical Device
Instrument Instrumentation
Bio(medical)instrumentation
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Definitions
Instrument : a tool used to facilitate work.
Instrumentation : 1) the application or use of
instruments, 2) the study, development, and
manufacture of instruments, as for scientific or
industrial use.
Instrument & Instrumentation 도구와 도구화(계측: 計셀계測헤아릴측)
The heart is the only broken
instrument that works.
- T. E. Kalem
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Sensor Analog signal processing A/D conversion
Main Control Unit
Digital Signal Processing
Data Input
User Interface
Calibration
Feedback Control
Actuator
BioSystem
measurand
Display Storage Xmission
target
Processor /Algorithm
Diagnostic Instrument
Therapeutic Instrument
Basic Bioinstrumentation System Electrical Energy Other types
of Energy vs
Electronic System
정의 2
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Processor & Algorithm Hardware & Software
• PC : general-purpose computer
• Embedded System : a special-purpose computer system designed to perform one or a few dedicated functions
• Programs : signal processing algorithm
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Sensors & Actuators As Transducers
변환기 (Transducer)
입력신호(에너지1) 출력신호(에너지2)
Transducer : A converter of one type of energy into another
Sensor : A transducer producing an electrical output
센서 (Sensor)
입력신호 (에너지1)
출력신호 (전기에너지)
Actuator : A transducer accepting an electrical input
작동기 (Actuator)
출력신호 (에너지2)
입력신호 (전기에너지)
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Actuators
• Mechanical – electrical motor, solenoid valve, piezoelectric
• Electrical - electrode
• Optical – LASER, LED, bulb
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Sensor characteristics
• Common characteristics – Accuracy : The ratio (expressed as a percentage) between the
true value minus measured value and the true value. (cf. precision) – Operating range : The maximum and minimum values that
can be accurately measured. – Response time : The time to reach 90% of the final value
measured. – Sensitivity : The ratio of the incremental sensor output to the
incremental input quantity. (cf. Selectivity) – Resolution : The smallest incremental quantity that the sensor
can measure with certainty. – Reproducibility : The ability of the sensor to produce the
same output when the same quantity is measured repeatedly. (cf. repeatability)
• In vivo characteristics – Safety and Efficacy/Effectiveness
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High accuracy, but low precision High precision, but low accuracy
Coefficient of variation : In probability theory and statistics, the coefficient of variation (CV) is a normalized measure of dispersion of a probability distribution. It is defined as the ratio of the standard deviation to the mean :This is only defined for non-zero mean, and is most useful for variables that are always positive. It is often reported as a percentage (%) by multiplying the above calculation by 100.
• Accuracy, Precision, and CV
Sensor characteristics
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Biostatics
Disease
+ -
Test
+ 9990
True Positive (TP)
990 False Positive
(FP)
All with Positive Test
TP+FP
Positive Predictive Value=
TP/(TP+FP) 9990/(9990+990)
=91%
- 10
False Negative (FN)
989,010 True Negative
(TN)
All with Negative Test
FN+TN
Negative Predictive Value=
TN/(FN+TN) 989,010/(10+989,010)
=99.999%
All with Disease 10,000
All without Disease 999,000
Everyone= TP+FP+FN+TN
Sensitivity= TP/(TP+FN)
9990/(9990+10)
Specificity= TN/(FP+TN)
989,010/ (989,010+990)
Pre-Test Probability= (TP+FN)/(TP+FP+FN+TN) (in this case = prevalence)
10,000/1,000,000 = 1%
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Mechanical
Thermal
Electrical
Magnetic
Radiant
Chemical
Stimulus/
Measurand
1. voltage,
current,
resistance, or
electric field
strength,
2. easy to
handle,
3. many good
tools are
ready,
4. PC
EtCO2
IR absorption
(2.7/4.3/14.7μm)
LED +
photo-
detector
Blood
Pressure
displacement
of diaphragm
strain
gauge
Transducible
Property
Principle of
Transduction
Detection
Means
Conversion
Phenomenon
SENSOR
Electrical
Output
Sensors - Definition and Principles -
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Principle of
Transduction
Detection Means Conversion Phenomenon
Physical
Chemical
Biological
Physical
Chemical
Biological
Physical
Measurand/
Stimulus
“biosensor” chemical sensor
physical sensor
Thermoelectric Photoelectric Photomagnetic Magnetoelectric Electromagnetic Thermoelastic Electroelastic Thermomagnetic Thermooptic Photoelastic
ECG, EEG, EMG Pressure Flow Temperature pO2 spO2 Glucose DNA/RNA protein
Biological Chemical Electric, magnetic EM wave Heat, temperature Displacement, wave Radiation Radioactivity
SENSOR
Transducible
Property Electrical Output
Sensor Classification
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biological detection element biolayer
Detection
transducer
Transduction
electronic signal
electronics
Output
Signal Conditioning
olfactory membrane
sample nerve cell brain
analyte (substrate)
impurity
Substances
바이오센서 정의(functional & structural)
High Selectivity & Sensitivity
Introduction to Biosensor
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• 측정대상 : Any substance that is consumed or produced in a biochemical process and exists inside human body
Ions Gases Drugs Substrates Enzymes Microbiology
Sodium Potassium
Calcium pH
Oxygen Ammonia
CO2
Paracetamol Slaicylate
Amphetamine Barbiturates
Cocaine Morphine
Glucose Cholesterol Creatinine
Creatine kinase Amylase
Aspartate Aminotransferase
Chlamydia Strep A Strep B H. Pylori
I.M. Malaria
Tuberculosis
Hormones Cardiac Markers
Proteins Allergy Renal Dysfunction
Tumor Markers Viruses
hCG
FSH
LH
Prolactin
TSH
CK-MB
Myoglobin
TroponinI
CRP
IgE
Micro-Albumin
PSA
Hemoglobin
AFP
Ferritin
Adenovirus
HBsAg
HBsAb
Rotavirus
R.S.V.
Introduction to Biosensor
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생물학적 감지요소
• Can attach/combine to one particular substrate but not to others
• High selectivity & sensitivity
• Examples Enzyme Antibodies Nucleic acids Receptors Microorganisms Cell/Tissue/Organ materials
Introduction to Biosensor
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고정방법
• Adsorption
• Microencapsulation
• Entrapment
• Cross-linking
• Covalent bonding
B B B
B B B
B B B
B B B
B B B
Introduction to Biosensor
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변환기(transducer)
• Electrochemical potentiometric, amperometric, voltammetric,
conductometric electrode, FET-based
• Optical absorption, fluorescence, luminescence,
IRS(ATR, TIRF, SPR), light scattering • Piezoelectric : QCM, EQCM • Surface Acoustic Waves • Thermal
Introduction to Biosensor
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“최초의 바이오센서는 혈당센서!”
OHeOHO 442 22
1956, L.C. Clark (oxygen electrode) Chemical Sensor
Glucose + O2 Gluconic acid + H2O2
GOD
1962, L.C. Clark (enzyme electrode)
Biosensor
GOD
Introduction to Biosensor
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Sensor Packaging
• Sensors for in vivo applications;
– Safe, functionally reliable
– Long operational lifetime, biocompatibility (esp. for implantable sensors) • Membrane fouling : protein adsorption, cellular response -
Change of membrane permeability – loss of sensitivity and stability
• Nonthrombogenic, nontoxic
• Polymeric covering materials
– Withstand sterilization procedure (steam, ethylene oxide, gamma radiation)
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• Measurand
– physical quantity, property, or condition that the system measures
– accessibility :
• internal (Blood Pressure)
• surface ( ElectroCardioGram, ECG or EKG)
• emanate from body (IR radiation)
• separated form body (sample) – in vitro
diagnostics
Sensing Parameters
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9.2 Biopotential Measurements
• Origin of Bioelectricity = action potential of
excitable cells
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Medical Devices based on Bioelectricity
“Sensor” “Actuator”
Bioelectricity Electrical Machine Electrical Machine
Electrode(전극) Electrode(전극)
Therapeutic Instruments Diagnostic Instruments
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Active cell bathing medium body surface (Constant Current Source) (Volume Conductor) (Potential Difference)
Na+ Cl-
BAT
e e V
sea
Biopotential Measurement- principle
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Source identification problem from projections
ECG lead EEG lead
Biopotential Measurement
v source lead
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ECG EEG EMG/EP
ENG,EOG,ERG ECoG,EGG,E氣G,ExG?
Bioelectric Signal Instruments
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ECG의 종류
28
심전도(Electrocardiogram)
심전도술(Electrocardiography)
심전계(Electrocardiograph)
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Cardiac Pacemaker
Cochlear Implant
Deep-brain Stimulator
Advanced Pain Therapy-Neurostimulation
Functional Electrical Stimulation - restoring function through electrical stimulation -
Electrical Stimulation
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World War I Navy ship spark-gap transmitter at Harvard Univ.
1925 : W.T. Bovie Harvey Cushing for neurosurgery
1950 : widely used with nonflammable anesthetics
Electrosurgical Unit(ESU) - Bovie
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radio frequency oscillator : 300kHz - 3 MHz, noise generator
voltages : 1,000 - 10,000 volts peak-to-peak
breakdown field intensity in air : 30kV/cm 0.33cm @ 10,000 V
mode select : cutting, coagulation
return electrode : low resistance
Electrosurgical Unit(ESU) - principle
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Equivalent circuit of a cell and tissue model
Let-go current from arm to arm as a
function of frequency
How doesn’t ESU produce electrical shock in patients? - 6.3A is required @ 500kHz to generate action potential - causing the cells to vaporize rather than depolarize
Electrical Safety - ESU
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Energy levels
- External defibrillation: 2 - 360 J
- Capacitor charging time: 8sec to 360J/4sec to
200J.
Defibrillation pulse
- Waveform: Damped sinusoidal halfwave (Edmark)
- Synchronized delay: @ 40 ms from R-wave trigger
Defibrillation electrodes
- Hard paddles: Hard paddles (80 cm2)
Pediatric adapter (17 cm2).
Defibrillator
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Cl- Cl- Cl-
Na+ Na+ Na+ Na+
e-
Electrode as a sensor : ion to free electron conversion
Biopotential Measurement-electrode
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Electrode - definition
• Electrolyte : a substance with ionic dc conductivity.
– Pure electrolytes: charge carriers are ions, no separate
flow of electron.
– Living tissue : electrolytic conductor (intracellular and
extracellular liquids contain ions free to migrate.)
• Electrode :
– Two current carrying electrodes in an electrolyte are
the source and sink of electrons
– The electrode is the site of a charge carrier shift, a
charge exchange between electrons and ions.
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EMG Surface Electrodes
Monopolar Needle Electrodes Concentric Needle Electrodes
EEG Single Disc Electrodes Disposable ECG Electrodes
Electrode Types
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9.3 Physical Measurements
• Pressure / Force
• Temperature
• Blood Flow
– Volume Flow
– Velocity
– Blood Volume Change
• Gas Flow
• Oxygen Saturation
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Unbonded Strain-Gauge
Pressure Sensor
(a) with increase pressure, the strain on
gage pair B & C is increased, while that
on gage pair A & D is decreased,
(b) Statham Pressure Transducer
P23XL
(a)
(b)
Pressure Measurement
Disposable Semiconductor
Pressure Sensor
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Strain Gage Sensor
• Strain Gage : a fine wire strained within its elastic limit converts extremely small displacement into resistance change due to changes in D, L, and
2
(1 2 )
(1 2 )
LR
A
dL ddR A LdA L
A A
R L A
R L A
R L
R L
R RG
L L L L
where Poisson’s ratio: D/D = - L/L
where gage factor G is useful in comparing various strain-gage materials
dimensional effect Piezoresistive effect
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Strain Gage Sensor
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Temperature Measurement
Tympanic thermometer
Respiration Detector
구강용 수은체온계
액와 수은체온계
항문용 수은체온계
이마용
액체 수은체온계
전 자 체 온 계 수은체온계
Infrared Pyrometer
thermistor
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Overview
The Thermocouple is a thermoelectric temperature sensor which consists of two dissimilar metallic wires, e.g., one chromel and one constantan. These two wires are connected at two different junctions, one for temperature measurement and the other for reference. The temperature difference between the two junctions is detected by measuring the change in voltage (electromotive force, EMF) across the dissimilar metals at the temperature measurement junction.
Typical Thermocouples
Thermocouple
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Overview
The Resistance Temperature Detector (RTD) or resistance thermometer uses the fact that the resistance of metals increases with temperature. Examples are RTD's are shown schematically below.
Resistance Temperature Detectors
RTD
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Thermistor Overview
Similar to Resistance Temperature Detectors (RTD), the Thermistor (Bulk Semiconductor Sensor) uses resistance to detect temperature. However, unlike an RTD's metal probe where the resistance increases with temperature, the thermistor uses ceramic semiconducting materials which respond inversely with temperature. Examples of thermistors are shown in the following schematic.
Typical thermistor sensors can measure temperatures across the range of -40 ~ 150 ±0.35 °C (-40 ~ 302 ±0.63 °F). The shape of the thermistor probe can take the form of a bead, washer, disk, or rod as illustrated in the above figure. Typical operation resistances are in the kW range, although the actual resistance may range from several MW to several W.
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Thermopile Overview
A thermopile is an electronic device that converts thermal energy into electrical energy. It is composed of several thermocouples connected usually in series. Thermopiles do not respond to absolute temperature, but generate an output voltage proportional to a local temperature difference or temperature gradient. Thermopiles are used to provide an output in response to temperature as part of a temperature measuring device, such as the infrared thermometers widely used by medical professionals to measure body temperature.
infrared thermometer module
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Measurement of Flow and Volume
of Blood
[O2] & other nutrients in the cells
Blood Flow
Blood Pressure
ECG
measurement
Primary
2nd
-class
3rd
-class
4th
-class
Difficulty
invasiveness
Quantity to be known
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Ci
Indicator’s input
concentration
Co
Indicator’s output
concentration
F : volume flow
dm/dt :rate of indicator injection
i o
o i
dmC F C F
dt
dm
dtFC C
Verify dimension (unit) of
flow F
• Concentration – principles of mass transport
INDICATOR-DILUTION METHOD
CONTINUOUS INFUSION
Volume flow
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• Fick Technique
a v
dm
dtFC C
Where
F : blood flow [L/min]
dm/dt : consumption of O2 [L/min]
= [O2] - [CO
2]
Ca : arterial concentration of O
2 [L/L]
Cv : venous concentration of O
2 [L/L]
Fig. 8.1 Several methods of measuring
cardiac output
INDICATOR-DILUTION METHOD
CONTINUOUS INFUSION
Volume flow
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INDICATOR-DILUTION METHOD
RAPID(Bolus) INJECTION
• equation
Bolus injection [m] Sampling site
dm/dV F
1
1
0
1
0
at sampling site
( )
( ) ( )
( ) or ( )
where t is the point C(t) reaches zero (pre-injection level)
( )
t
t
dm C t dV
dm dVC t C t F
dt dt
dm C t Fdt m F C t dt
mF
C t dt
Fig. 8.2 Rapid injection indicator-
dilution curve
Volume flow
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• Dye dilution
– Indocyanine green(cardiogreen)
– Optical absorption peak at 805nm
(independent of blood oxygenation)
– Injected into pulmonary artery
– Concentration curve obtained at femoral
or brachial artery
Volume flow
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where Q : heat content of injectate [J = ViΔT
iρ
ic
i]
ρb : density of blood [kg/m
3]
cb : specific heat of blood [J/kg°K]
• Thermodilution
– Cold saline
– 4-lumen catheter (Swan-Ganz catheter)
1
0
( )
t
b b b
QF
c T t dt
Volume flow
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ELECTROMAGNETIC FLOWMETERS
• PRINCIPLE – Faraday’s law of induction
1
0
L
e u B dL
where B : magnetic flux density (T or Wb/m2)
L : length between electrodes (m)
u : instantaneous velocity of blood (m/s)
Fig. 8.3 Electromagnetic flowmeter
Velocity
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ULTRASONIC FLOWMETERS
• Transit-time Flowmeter
2 22 2
distance
conduction velocity cos
2 cos 2 cos
cos
(nsec order)
Dt
c u
Du Dut
cc u
u t
Velocity
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• Continuous–wave Doppler Flowmeter
Velocity
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THERMAL-CONVECTION
VELOCITY SENSORS
• Principle :
logW
a b uT
where W : power dissipated by current passing through Ru,
ΔT : temperature difference above blood temperature,
u : blood velocity
• Probes :
Fig. 8.13 Thermal velocity probes
Velocity
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•Plethysmography is a test used
to measure changes in blood
volume or air volume in different
parts of the body.
•Photoplethysmography (PPG)
is the electro-optic technique of
measuring the cardiovascular
pulse wave found throughout the
human body
Volume Change Measurement
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MEASUREMENT OF
GAS-FLOW RATE
Fig. 9-3 Pneumotachometer for measurements at the mouth
P=f(Q)
- differential pressure flowmeters (pneumotachometers)
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- Turbine flow meter
http://spirxpert.com/technical.htm
MEASUREMENT OF
GAS-FLOW RATE
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- Hot wire anemometer
- A chip is required to linearize the output
of hot wire anemometers.
- As anemometers are insensitive to the
direction of flow, two heated wires need
to be placed in series; the flow direction
can then be determined from the wire
that cools first.
- A disadvantage of this type of meter is
its sensitivity to gas composition and
gas temperature; in addition these
measuring systems are very vulnerable
to damage and need to be handled with
special care.
http://spirxpert.com/technical.htm
MEASUREMENT OF
GAS-FLOW RATE
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Pulse oxymeter analyzes the light absorption at two
wavelengths of only the pulse-added volume of oxygenated
arterial blood.
① transmission type : fingertips, toes, ear lobes, or nose
② reflectance type : at various locations on the body surface
including more central locations (such as chest, forehead, and
limbs)
NONINVASIVE BLOOD-GAS MONITORING
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-Beer's law : "equal thickness of an absorbing material will absorb
a constant fraction of the energy incident upon it"
where P0 = radiant power arriving at the cuvette
P = radiant power leaving the cuvette
a = absorptivity of the sample
L = length of the path through the sample
C = concentration of the absorbing substance
Absorbance A is defined as log(P0/P), so
: obey Beer's law.
where u : for unknown concentration material
s : for standard material
010 aLCP P
0log( )
( )uu s
s
PA aLC
P
AC C
A
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Ext = the extinction coefficient, function of & absorber, c = the concentration of a single light absorber, d = thickness of absorber
)exp(
][][
][
0
2
22
dcExtII
HbOHb
HbOSO
4 unknowns
Oxygen Saturation - Pulse Oxymetry (SpO2)
Lambert-Beer’s Law
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),(),()),(),((
),(),(
),()1)(,(
),()1)(,(
)(I
)(Iln
)(I
)(Iln
]))[,(])[,(()(I
)(Iln
])))[,(])[,((exp()(I)(I
)),(exp()()(I
112222
122
22222
21221
2m
2m
1m
1m
22
m
m
22mm
1
m
HbExtHbOExtHbOExtHbExtR
HbExtHbRExtSpO
SpOHbOExtSpOHbExt
SpOHbOExtSpOHbExtR
HbOHbOExtHbHbExtd
HbOHbOExtHbHbExtd
dciExtI
in
ax
in
ax
in
ax
axin
N
i
iiLEDax
Oxygen Saturation - Pulse Oxymetry (SpO2)