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Fabrication and Study of an Optic Meter for the Hematological

Analysis

Final Year Design Project Report

Advisor

Dr. Hassan Sayyad

Co Advisor

Dr. Ikram Trimizi

Submitted by

M. Suwaid Khan 2005174

M. Owaim Khalid 2005168

Momina Rajput 2005143

Hira Asad 2005090

Faculty of Engineering Sciences

Ghulam Ishaq Khan Institute of Engineering Sciences and Technology.

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Acknowledgements

First, we would like to thank ALLAH Almighty for bestowing us with

knowledge, courage and hope to do this project. It required hard work and

perseverance that we were unable to achieve without the shadow of ALLAHs

help.

Second, we would like to thank our professors who being the guidelines and

support for us helped us in accomplishing the task at our hands. Our project

advisor Dr. Hassan Sayyad for being the complete support and motivation for

us and helped us through every stage of our project. He made this project a

success. We owe our entire project to his help and appreciate his for giving us

so much time out of his hectic schedule. We all are so grateful to him.

We got support intellectually by Brig. Dr. Rizwan Hashim, Head of

Department of Armed Forces Institute of Pathology. It was indeed an honor

interacting with such an intelligent person. He had so many brilliant ideas and

interesting points that we were greatly motivated and learnt new experience.

He really helped us all the way with his command on knowledge and

engineering technology. We would always miss working with him. It was a

great learning experience.

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ABSTRACT

To develop a systems Prototype by means of which Diabetes Mellitus Patients

would be able to monitor their sugar level, oxygen level and pulse rate by the

Non-invasive technique and record data into a data base of their home

computer, i.e. A device which consist of small circuitry for measuring oxygen

level and pulse rate with the integrated system of polarizer and laser for the

non-invasive glucose measurement which can be easily afford by every class

of people and is also pretty much safe from the hygienically point of view as

compared to the other glucose measuring systems. This will save a time and

also keeps records for any future complications. There is no need to go to

doctor because it also provides ease of electronically mailing the medical

history regarding glucose measurements.

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TABLE OF CONTENTS

Contents

TABLE OF CONTENTS ......................... ........................... .......................... ............................ ................. 4

Chapter No.1 The Gluco-Meter .......................... ........................... ......................... ....................... 6

1.1 Introduction .................................................................................................................................... 6

1.2 Types of Measurement Techniques .......................... ......................... ............................. ................ 7

1.2.1 Common Features of Non-Invasive Optical Techniques............................................................ 8

1.2.2Fluid Glucose Optical Measurement Strategies....................................................................... 10

1.3 The method used for glucose monitoring ............................. .......................... ......................... 12

1.3.1 Theory............................................................................................................................ 121.3.2 Experimental setup and procedure ................................................................................. 12

1.3.3 Processing ofthe signal................................................................................................... 14

1.4 Problems occurred and there solution. ......................... ......................... ............................ ...... 20

1.5 Results obtained ...................... ........................... ......................... ............................ ............... 22

&RQFOXVLRQV&KDOOHQJHVDQG,VVXHV5HTXLULQJ)XUWKHU6WXG\

CHAPTER No. 2 Oximeter ........................ ............................ ......................... ............................ ...... 25

2.1 Introduction: ........................................................................................................................... 25

2.2 Significance: ....................... ........................... .......................... ............................ ................... 25

2.3 Hardware Setup: .................................................................................................................... 26

2.4 Design Criteria: ........................ ........................... ......................... ............................ ............... 27

2.5 Design & Process: ....................... ........................... ......................... ............................. .......... 27

2.5.1 Pre-Existing Probe Reverse Engineering.......................................................................... 27

2.5.2 Complete Probe and Circuitry Prototype Construction .................................................... 28

2.6 Design Evaluation & Results: .......................... ......................... ............................ ................... 32

Chapter No. 3: Pulse Meter ........................ ........................... .......................... ............................ . 37

3.1 Introduction: ........................................................................................................................... 38

3.2 Working Principle:................................................................................................................... 38

3.2.1 Block Diagram................................................................................................................. 39

3.2.2 Signal Acquisition............................................................................................................ 39

3.2.3 Signal Conditioning ......................................................................................................... 39

3.2.4 Signal Manipulation ........................................................................................................ 40

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3.3 Circuit Components: ......................... .......................... .......................... ............................ ...... 40

3.3.1 Red LEDs:........................................................................................................................ 40

3.3.2 LDR ................................................................................................................................. 41

3.3.3 Filters: ............................................................................................................................ 42

3.3.4 Amplifiers: ...................................................................................................................... 43

3.3.5 Capacitors:...................................................................................................................... 44

3.3.6 Display:........................................................................................................................... 45

3.4 Features And Advantages of Pulse Meter: ....................... .......................... ............................ . 46

3.5 Sources of Error in the Circuit: ........................ ......................... ............................ ................... 46

3.6 Ways of Overcoming Errors ........................... ......................... ............................. .................. 46

3.7 Conclusion: ............................................................................................................................ 46

BIBLIOGRAPHY:..47

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Chapter No.1 The Gluco-Meter

1.1 Introduction

Diabetes mellitus is a medical condition in which the body does not adequately

produce the quantity or quality of insulin needed to maintain normal circulating blood

glucose. Insulin is a hormone that enables glucose (sugar) to enter the bodys cells to be

used for energy. Two types of diabetes are common. Type-I is also known as Insulin

Dependent Diabetes Mellitus (IDDM) and accounts for 5-10% of all cases. Type-II or

Non-Insulin Dependent Diabetes Mellitus (NIDDM) occurs in 90-95% of the diabetic

population. In IDDM, the disease occurs in childhood and requires insulin doses tomaintain life, in addition to healthy eating and exercise. NIDDM occurs later in life-

perhaps after 40 years of age and may require insulin or be controllable with oral

medication, weight loss, a nutritious diet and a regular exercise program.

It is estimated that diabetes afflicts nearly over 100 million people worldwide.

Diabetes is the fourth leading cause of death by disease in the United States, killing more

than 169,000 people each year1. Frequent self-monitoring of blood glucose is crucial for

effective treatment and reduction of the morbidity and mortality of diabetes.

Diabetes can lead to severe complications over time, including blindness, kidneyfailure, heart failure, and peripheral neuropathy associated with limb pain, poor

circulation, gangrene and subsequent amputation (2). According to the American Diabetes

Association (ADA) complications arising from diabetes cost the US health care system in

excess of $45 billion. These complications are largely due to years of poor glucose

control. The Diabetes Care and Complications Trial (DCCT) demonstrated that more

frequent monitoring of blood glucose and insulin levels could prevent many of the long

term complications of diabetes (3). However, current blood (finger stick) glucose tests are

painful, inconvenient due to disruption of daily life, cause fear of hypoglycemia resulting

from tighter glucose control and maybe difficult to perform in long term diabetic patients

due to calluses on the fingers and poor circulation.

Thus, the average diabetic patient tests his/her blood glucose levels less than

twice a day versus the recommended 4-7 times per day. A non-invasive method (fast,

painless and convenient) for glucose monitoring could provide adequate control and

greatly reduce the complications seen in these patients and consequently reduce health

care costs.

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Currently glucose measurements are done by pricking a finger and extracting a

drop of blood which is applied to a test strip composed of chemicals sensitive to the

glucose in the blood sample. An optical meter (glucometer) is used to analyze the blood

sample and gives a numerical glucose reading. The various types of glucometers sold

usually cost less than $100 dollars or have been discounted greatly because of the

purchase of expendable, one-use-only test strips. These strips cost 50 cents ($0.50), a

modest cost if only a small use rate is required. A strip used every day costs about

$183.00 per year for the diabetic that tests only one time a day. Those requiring multiple

measurements (the elderly and children etc.) would easily have much higher yearly costs.

These figures and the revenue potential make development of the non-invasive glucose

sensor a most sought after device.

1.2 Types of Measurement Techniques

Non-invasive glucose monitoring techniques can be grouped as subcutaneous,

dermal, epidermal and combined dermal and epidermal glucose measurements.

Matrices other than blood under investigation include interstitial fluid, ocular

fluids and sweat. Test sites being explored include finger tips, cuticle, finger web,

forearm and ear lobe. Subcutaneous measurements include micro dialysis, wick

extraction, and implanted electrochemical or competitive fluorescence sensors. Micro

dialysis is also an investigational dermal and epidermal glucose measurement technique.

Epidermal measurements can be obtained via infrared spectroscopy, as well. Combined

dermal and epidermal fluid glucose measurements include extraction fluid techniques

(iontophoresis, skin suction and suction effusion techniques) and optical techniques. The

optical techniques include near infrared spectroscopy, infrared spectroscopy, Raman

spectroscopy, photo acoustic spectroscopy, scatter and polarization changes (4). This

overview is focused on a description of the optical techniques (Table 1) currently under

development by diagnostic equipment manufacturers for glucose monitoring in diabetics-the fastest growing segment of diagnostic testing.

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1.2.1 Common Features of Non-Invasive Optical Techniques

Non-invasive optical measurement of glucose is performed by focusing a

beam of light onto the body. The light is modified by the tissue after transmission

through the target area. An optical signature or fingerprint of the tissue content is

produced by the diffuse light that escapes the tissue it has penetrated. The

absorbance of light by the skin is due to its chemical components (i.e., water,

hemoglobin, melanin, fat and glucose). The transmission of light at each

wavelength is a function of thickness, color and structure of the skin, bone, blood

and other material through which the light passes (4).

The glucose concentration can be determined by analyzing the opticalsignal changes in wavelength, polarization or intensity of light. The sample

volume measured by these methods depends on the measurement site. The

correlation with blood glucose is based on the percent of fluid sample that is

interstitial, intracellular or capillary blood. Drs. Roe and Smoller (4) have devised

the following example. The fluid viewed through the limb is 63% intracellular

and 37% extracellular, of which 27% is interstitial and 10% plasma. A blood

glucose value of 100mg/dl is equivalent to a tissue sample glucose average of

38mg/dl of which 26% is due to blood, 58% is due to interstitial fluid and 16% is

due to intracellular fluid. What the tissue sample glucose means clinically in

respect, to therapy is still under investigation.

Not only is the optical measurement dependent on concentration changes

in all body compartments measured, but changes in the ratio of tissue fluids (as

altered by activity level, diet or hormone fluctuations) and this, in turn, effects the

glucose measurement. Problems also occur due to changes in the tissue after the

original calibration and the lack of transferability of calibration from one part of

the body to another. Tissue changes include: body fluid source of the blood

supply for the body fluid being measured, medications that affect the ratio of

tissue fluids, day-to-day changes in the vasculature, the aging process, diseasesand the persons metabolic activity.

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Dermal and Epidermal*Fluid Glucose Measurement Techniques

Technique Definition

Near Infrared Spectroscopy (NIR) Absorption or emission data in the 0.7 to

2.5 m region of the spectrum are

compared to known data for glucose.

Raman Spectroscopy Laser light is used to induce emission from

transitions near the level excited.

Photo acoustic Spectroscopy Laser excitation of fluids is used to

generate an acoustic response and a

spectrum as the laser is tuned.

Scatter Changes The scattering of light can be used to

indicate a change in the material beingexamined.

Polarization Changes The presence of glucose in a fluid is known

to cause a polarization preference in the

light transmitted.

Mid-Infrared Spectroscopy Absorption or emission data in the 2.5 m -

25 m region are examined and used to

quantitative glucose in a fluid.

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1.2.2Fluid Glucose Optical Measurement Strategies

1.2.2.1 Near Infrared Spectroscopy (NIR)

Glucose produces one of the weakest NIR absorption signals per

concentration unit of the bodys major components. NIR spectroscopy

glucose measurement enables investigation of tissue depths in the range of 1

to 100 millimeters with a general decrease in penetration depth as the

wavelength value is increased. NIR transmission through an ear lobe, finger

web and finger cuticle or reflected from the skin of the forearm and lip

mucosa has been attempted in the NIR region between 1000nm to 2500nm.

NIR diffuse reflectance measurements have been performed on the finger

and cuticles have shown good correlation with blood glucose but 10% of the

predictions are not clinically acceptable [5].

Diffuse reflectance studies of the inner lip also have shown good

correlation with blood glucose and indicated a time lag of 10 minutes

between blood glucose and the measurement signal [6]. Salivary glucose

levels (a component of lip measurements) did not reflect blood glucose

levels. Physical and chemical parameters such as variation in pressure,

temperature, triglyceride and albumin interfere with glucose measurement.

Errors can also occur due to environmental variations such as changes in

temperature, humidity, skin hydration, carbon dioxide, and atmospheric

pressure [4]. Extensive validation and testing of the glucose prediction

equation is needed to determine if the glucose correlation is consistent in all

clinically important conditions in all types of patients.

1.2.2.2 Infrared Spectroscopy (IR)The IR glucose measurement systems at the epidermal surface

enables investigation of tissue depths in the range of 10 to 50 micrometers at

using a wavelength band in the IR region from 700 to 1000nm [7]. These

systems do not measure glucose in the blood containing tissues. Anattenuated total reflection technique has been used for oral mucosa;

however, the drawbacks include glucose contamination of the measurement

site by food and highly variable saliva of low rate [8]. Assays using used

whole blood as the sample matrix are subject to interferences due to

albumin, red cells and gamma globulin and changes in temperature and pH.

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Further, saliva glucose varies considerably and does not reflect blood

glucose methods [4].

1.2.2.3 Raman Spectroscopy

Raman spectroscopy measures scattered light that has beeninfluenced by the oscillation and rotation of the scatter. Various Raman

techniques have been attempted in blood, water, serum, and plasma

solutions and the eye, but multiple problems remain before human studies

can be performed. Analytical problems include instability in the laser

wavelength and intensity, errors due to other chemicals in the tissue sample

and long spectral acquisition times [4].

1.2.2.4 Photo Acoustic Spectroscopy

Photo acoustic spectroscopy uses an optical beam to rapidly heat the

sample and generate an acoustic pressure wave that can be measured by a

microphone. The determination of glucose in blood [9], tissue phantoms [10]

and humans [11] can provide greater sensitivity than conventional

spectroscopy when specific physical parameters are favorable. Excellent

correlations between the photo acoustic signal and blood glucose levels have

been shown on index fingers of healthy and diabetic patients. The

instrumentation is currently custom made, expensive and sensitive to

environmental parameters. The technique is also subject to chemical

interferences from biological molecules as well as physical interferencefrom temperature and pressure changes.

1.2.2.5 Scatter Changes

Scatter measurement monitors the changes in tissue reduced

scattering coefficient and is used for the determination of glucose in tissue

phantoms and humans.

Increased glucose in the sample is proportional to an increase in the

refractive index of the sample and thus the particle scattering properties ofthe sample are changed. Measurements on the abdomen of the diabetic

patients showed excellent correlation between the scatter signal and blood

glucose levels [12]. Many parameters contribute to a natural physiological

drift of the scattering parameter. Methods are needed to compensate for the

signal drift.

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1.3 The method used for glucose monitoring.1.3.1 Theory.

Although the change in optical signal by glucose is small, glucose is a

good optical rotator. This characteristic has been used to conduct in-vitro glucoseassays [13]. The intensity of light corresponds to the amount of light present. The

method we used for the glucose monitoring was the measurement using polarized

laser and the basic principal behind this technique is:

When a plane polarized light (He-Ne Laser) is passed through a glucose

solution (blood) it observes a rotation in its plane of polarization, depending upon

the concentration of glucose.

As we know that polarization is the phenomenon in which waves of light

or other radiation are restricted in the particular direction of vibration.

So what we did was the division of beams of light into separate planes or

vectors by means of polarizing filters in order to observe the rotation is its plane

of polarization using the appropriate polarizers.

1.3.2 Experimental setup and procedure.The experimental setup we used to measure the glucose level can be

explained by the flowing flow chart.

LASER (He-Ne

4mW)

Vertical

PolarizerSAMPLE

Vertical

PolarizerGeneration of

signal (LDR)

Processing of

signal

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The first issue at hand was the selection of an appropriate Laser, with a

particular wavelength which can b absorbed by the blood and gets rotated by itunique property; So we searched about it and found that the required Laser is the

one with wavelength in the red region (near 690nm), therefore we used He-Ne

Laser with worked perfectly according to out requirements. And also that we

needed such a Laser which was powerful enough to pass through the skin of a

human with the significant amount of information we need to measure the degree

of rotation cause by the glucose concentration present in the human blood;

without causing damage to the human skin, since we are intended to use this

device (gluco-meter) many times a day. We started out experiments with 1mW

laser n found it too week for our need to measure the degree of rotation. So we

tried 2 and 3 mW lasers and finally we got the satisfying results by using the4mW He-Ne Laser.

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The 4 mW He-Ne Laser was first vertically polarized and then passed

through the sample, where it gets rotated according to the concentration of the

glucose present in the sample; this degree of rotation was determined by the 2 nd

polarizer and then the final signal was obtained using the LDR (light dependant

resistor) which was further processed.

In order to measure the degree of rotation we 1st calibrated the two

polarizes but rotation of 10 degrees. The limitation of the polarization setup we

were using was sensitive only to the 10 degrees of rotation. This was the reason

we used the blood plasma cerium for our project instead of real specimen. We

tried a lot to get more sensitive polarizers but found out that they were very

costly and require a lot of time for the shipment to bring them to us from abroad.

So we went on with the available ones.

The next task at hand was to detect the signal coming out of the second

polarizer, for that we had various options, we could use either the photo detectorsor the light dependant resistors (LDR). We went for the light dependant resistors

because it was relatively cheap and readily available.

After finalizing the use of LDR for detecting the signal we had to take care

of the external noise, which was caused by the light coming towards the LDR

from the external light sources, for that was switched off the light while taking the

reading. Along with that we made a wooden box which was covered with a black

cloth, so that the reflected light form the LDRs surface cant be reflected back to

the LDR.

The signal obtained from the LDR was actually the change in the

resistance due to the detected light. In order to process that signal we needed it to

be in the form of voltage variation, so that we can interface it to the computer and

use to calculate the glucose level. This was done using a simple potential divider

circuit, which gave us the change in resistance into equivalent change in voltage

which was further processed.

1.3.3 Processing of the signal.The signal obtained from the potential divider circuit was in the form ofthe change in voltage. This change in voltage is then sent to the computer

using 89C51 microcontroller. We used 24-bit ADC in order to convert the

analog data into digital. Data manipulation was done in two part:

I. Feeding signal to the Microcontroller.

II. Processing the acquired voltage difference in computer (using

MATLAB).

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1.3.3.1 Feeding signal to the Microcontroller:

First of all the value that we obtained from our circuit is fed into the

microcontroller using RS232.

CODE: Code we used to get the value from the circuit is as

follows:

#include void delay_ms(unsigned int);void wait_DRDY();void delay_us(unsigned int);void write_ADS12(unsigned char);unsigned char read_ADS12();

//P2.2 now = DRDY//P2.1 = SCLK

//P2.0 = SDIO

void main (void){// unsigned char ftemp1,ftemp2,ftemp3,ftemp4;// unsigned char voltage;

unsigned char index, i;unsigned char d[3];unsigned char mybyte = 0;

TMOD = 0x20;TH1 = 0xFD;SCON = 0x50;TR1=1;

P2_2 = 1; // make input

delay_ms(100);

wait_DRDY();write_ADS12(4);write_ADS12(80); // originally 80wait_DRDY();write_ADS12(5);write_ADS12(0);

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// while (mybyte -=5)// {// while(RI==0);// mybyte = SBUF;// RI = 0;

// }

while(1){

wait_DRDY();write_ADS12(192);for (index = 0 ; index < 3; index++)

{d[index]=read_ADS12();//P2 = d[index];}for (i = 0 ; i < 3; i++){

SBUF = d[i];while(TI==0);TI=0;}

delay_ms(150);}

}

void delay_ms(unsigned int itime){unsigned i, j;for(i=0;i

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void wait_DRDY(){//probe_status |= 2;

while (P2_2 == 0) ;}

void write_ADS12(unsigned char data1){

unsigned char i, temp;

delay_us(40);for(i=0; i>7;data1 = data1

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P2_1 = 1;delay_us(10);data2 = data2

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total = ptop2 * 65536 + ptop1 * 256 + ptop0

x = total * 5 / 8388608;

% dist=fittedmodel1(x)

% LSB=dec2bin(ptop,8);

% value=strcat(MSB,LSB)

% value=bin2dec(value);

end

fclose(ser);

Picture of the DATA Acquisition & Processing

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1.4 Problems occurred and there solution.While working on this part of the project we came across a significant no ofproblems, few of them I would like to mention here due to there importance.

1.4.1 Sensitivity of LDR.

The main issue we first encountered was the requirement of a very

sensitive sensor. We opted the LDR as discussed earlier due to it various

advantages, i.e. it was cheap, very sensitive, and readily available. The problem

occurred after the selection of the sensor was to use it in such a way that the

external noise was not interfering with the original signal. What we did was that

we took all the readings at night and after turning off all the lights. That is how wemanaged to obtain error free results. An other effort we made to minimize this

problem was that, we made a wooded box which was covered with a black cloth,

to cover the whole experimental setup. So that the reflected light from the plastic

surface of the LDR was not reflected back to the sensor and add up as noise.

That is how we managed to reduce noise as far as the sensor was concerned.

1.4.2 Decrease in the blood glucose concentrationAs we discussed earlier that due to the low sensitivity of out polarizers we

had to use the blood plasma serum. And while working with the blood

plasma serum we came across a strange problem that was the decrease in

the blood glucose concentration. This decrease in the concentration was

(10mg/dl) per hour. In order to solve this problem we had to keep the

plasma serum at below 8 degree Celsius. And also that if we had to use the

sample for more than two days we had to freeze the sample.

1.4.3 Measuring the offsetThe next problem was to measure the offset we were getting due to various

factors and incorporate it in the readings. The first offset was due to the

test tube we were using for measuring the degree of rotation in the blood

plasma serum. It was then adjusted in the original reading.

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1.4.4 AccuracyAs we all know for the range of the normal blood glucose levels is:

Range:

Normal(fasting) 70-115 mg/dl

Normal(random) 80-160 mg/dl

Since we have discussed the limiting factor of our hardware due to which

we were unable to achieve the accuracy of 1mg/dl. So what we tried to do

is that we have proved by a multiple readings that the method we intended

to use is a right one to use for a non-invasive gluco-meter. With the same

limited hardware you can find that either your blood glucose level is in the

normal range, higher or lower.

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1.5 Results obtainedIn order to obtain a significant amount of accuracy in the results we first

calibrated the second polarizer as shown in the table below.

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We did the whole 360 calibration in order to check that either the polarizer is

homogeneous or not. Its obvious that the readings the repeating in a sinusoidal

manner which verifies the homogeneity of the polarizer we are using.

blood plasma(148

mg/dl) suger(100 mg/dl) bsf(133mg/dl) bsf(93mg/

voltage 1.37v 1.65v 1.52v 1.70v

voltage+offset(0.69) 2.06v 2.34v 2.21v 2.45v

degree of rotation 15 degrees 5 degrees 10 degrees 3 degrees

Shown above are some of the readings we took using the apparatus and it clearly

shows that as the concentration of the glucose in blood increases so does the

degree of rotation. This proves our theory. But yet we are a long distance away

from achieving our ultimate goal of integrating all the three modules.

1.6 Conclusions, Challenges and Issues Requiring Further StudyDiabetes mellitus is a complex group of syndromes that have in common adisturbance in the bodys use of glucose, resulting in an elevated blood sugar. Once

detected, sugar diabetes can be controlled by an appropriate regimen that should

include diet therapy, a weight reduction program for those persons who are

overweight, a program of exercise and insulin injections or oral drugs to lower

blood glucose. Blood glucose monitoring by the patient and the physician is an

important aspect in the control of the devastating complications (heart disease,

blindness, kidney failure or amputations) due to the disease. There is no cure.

Intensive therapy and frequent glucose testing has numerous benefits. Dr.

William Herman and his colleagues have determined that intensive therapy delays

the time to first complication by about 15 years, blindness by about eight years and

end-stage renal disease and lower extremity amputation by about six years. Further,

intensive therapy prolongs the life of the diabetic by about five years at a cost of

about $30,000 per life year gained [3].

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With ever improving advances in diagnostic technology, the race for the next

generation of bloodless, painless, accurate glucose instruments has begun.

However, many hurdles remain before these products reach the commercial

marketplace.

Calibration of the instruments and validation of the results obtained by the optical

methods under different environmental conditions and used by different patient

populations (i.e., different ages, sizes and ethnic origins) must be performed. The

devices may have to be calibrated to individual users.

Current instrumentation lacks specificity due to substantial chemical and physical

interferences. The devices use multivariate regression analyses that convert the

optical signal to a glucose concentration. Large amounts of data are used to build

the glucose model and must take into consideration the concentration range,

sampling environment and other factors involved in the analysis. First an

instrument must be designed that accurately detects glucose concentration.

Correlation and clinical interpretation of this value, in respect to the patients true

glucose value, is imperative for optimum therapy and disease management.

Considerable progress has been made in the development of non-invasive glucose

devices however, at this time; frequent testing using invasive blood glucose

determination via finger stick provides the best information for diabetes disease

management. Industry spokespersons have said: anyone who can come up with

a viable noninvasive or painless technique is going to make a lot of money.Peoples lives are involved ... and we dont want to suggest that this technology is

right around the corner. This is very tricky, difficult work.[14].

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CHAPTER No. 2 Oximeter

2.1 Introduction:

Pulse oximetry is a method used to measure oxygen saturation levels in the blood

non-invasively. This measurement is not only crucial to grown patients undergoing

anesthesia, but is also of great value to babies undergoing similar procedures. While

pulse oximetry is relatively easy to employ on grown human, it is often difficult to obtain

a signal in babies. The goal of this project is to modify a pulse oximeter design such that

oxygen saturation levels can be measured economically and effectively in small children

and babies. The primary approach is to build a pulse oximeter sensor using two lightemitting diodes (LEDs) and two photodiodes, which will be connected to amplification

circuit and then fed to a Microcontroller and then to computer and by using Agilent

software process the results. Empirical relationships will yield SaO2 values. The

deliverable of this project is a pulse oximeter design that is capable of detecting

hemoglobin (Hb) saturation levels in small children and babies in the range of 65 -95%.

2.2 Significance:

The percentage of Hb in the blood that is saturated with oxygen can tell a

physician a great deal about a patients health status and in particular, can indicate

whether the patient is receiving enough oxygen to his or her vital organs. Pulse oximetry

is a quick, effective, non-invasive approach that uses light sources and photo detectors

with the goal of measuring blood oxygenation. In addition to its use in humans, pulse

oximetry plays a vital role in the animal research realm; the monitoring of blood oxygen

levels during surgeries and anesthesia is equally as important in animals as in humans.

While sensors suiting larger species of animals currently exist, a pulse oximeter small

enough to use on a baby finger and sensitive enough to detect the pulsatile signal of a

baby that is up to 140 pulse per minute or faster than that, though the development ofsuch a device is crucial for the advancement of small babies and animals research,

because animals like mice have pulse rate equals 6 times of a normal human being. An

effective, economical, non-invasive means by which to monitor blood oxygenation in

mice also would benefit investigators and animal well-being alike.

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2.3 Hardware Setup:

The basic concept behind pulse oximeter technology is that as infrared light (850-

1000 nm) and red light (600-750 nm) are being transmitted through the skin and absorbed

at different levels at these two wavelengths by oxygenated and deoxygenated

Hb. Deoxygenated Hb allows more infrared light to pass through and thus absorbs more

red light than oxygenated Hb. After the two wavelengths of light have been transmitted

through tissue and received by a photodiode, the ratio of red/infrared light intensity is

computed. The hemoglobin saturation can therefore be determined by the level of light

intensity incident at the two photodiodes. This process is illustrated as a general

schematic below in figure 1:

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2.4 Design Criteria:

This project is a sensor that will successfully be used to measure the hemoglobin

SaO2 of a baby as well as mouse. The device will attach to a baby finger and mouse tail and

will be capable of doing the following:

y Measure mouse hemoglobin SaO2 levels of 65 95%

y Work in a range of average mouse heart rates of approximately 400-600 beats per minute

y Fit comfortably on a mouse tail of approximately 3-5 mm diameter.

2.5 Design & Process:

2.5.1 Pre-Existing Probe Reverse Engineering

Following a generous donation of a pulse oximeter probe from AFIP, our

previously-proposed primary approach was modified: instead of using the system to

attempt to obtain SaO2 readings, we decided to attempt to reverse-engineer the donated

probe using pin-out diagrams also secured through AFIP. The V3087 Mini Clip Sensor

can be seen below in figure-2.

Figure 2 (V3087 Mini Clip Sensor)

Before undertaking this task, a preliminary circuit diagram and design were

completed, and transimpedance op-amps that are specifically used in photodiodeamplification. Using a female 9 pin connector, we accurately identified and powered the

pins on the device which controlled the LEDs. We also identified the pins contributing to

the Red/IR LED alternating feature of the probe and were able to supply the probe with

an appropriate signal using the labs signal generator. To complete the preliminary stage

of this process, we constructed an amplification circuit into which we were able to

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incorporate power, the generated signal, and the probe; using the oscilloscope, we saw a

very noisy output signal.

Finally we came to know that the sophistication of the probe would probably

prevent us from successfully removing noise and acquiring a workable signal, forcing our

group to take on a third design attempt.

2.5.2 Complete Probe and Circuitry Prototype Construction

The pulse oximeter design consists of LED excitatory circuits as well as

photodiode sensory circuits; the receiving circuits convert the red and infrared light

currents into voltages which can then be observed using an oscilloscope. Signal voltage

data is then be recorded and post-processed in excel in order to obtain blood oxygen

saturation levels. The approach can be broken down as follows:

1) Two light emitting diodes (LEDs), of red (600 to 750 nm) and infrared (940 nm)

wavelengths, were directed at tissue and activated by an excitatory circuit.

2) The light emitted from the LEDs were transmitted through the skin and detected by two

photodiodes. An infrared rejection filter photodiode was then placed across from the red

LED in order to detect transmitted red light and prevent infrared light interference.

Similarly, a visible light rejection filter photodiode was placed across from the infrared

LED with similar intentions.

3) The two photodiodes were then connected to a transimpedance amplification circuit that

converted the current to an appropriately-enhanced voltage signal. The general circuit

diagram for each photo diode are shown below in Figure 3 (Red Photodiode) and figure 4

(Infrared Photodiode). The circuitry when these two circuits are combined can be seen in

figure 5.

Figure-3 & Figure-4

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4) The output voltage was then observed through the use of an oscilloscope. The output

voltage received when a human was tested can be seen below in figure 6.

Figure 6 (human output voltage on oscilloscope)

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5) This oscilloscope signal was then acquired in a PC through the use of an RS32 connection

and Agilent waveform processing software. The data was placed into files readable by

excel, and were subsequently processed. The results can be seen below in figure 7

(Voltage Output from Red Photodiode) and figure 8 (Voltage Output from IR

Photodiode).

Figure 7 Figure 8

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6) The design accuracy was subsequently verified through intense calibration and

experimentation procedures. The results of these verification processes can be found in

the Design Evaluation section.

2.6 Design Evaluation & Results:

One of the first tests run on our device was performed by placing pieces of paper

between the LEDs and their corresponding photodiode. As more pieces of paper were

placed between the clamps, the intensity of light reaching the photodiodes was expected

to decrease. The results can be seen in figure 9 (Red log fit) and figure 10 (IR log fit).

Figure-9

Figure 10

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The curves displayed in the above figures show that our device works under Beer's Law

(equation 1). Where I=t and VoI.

(equation 1) I=Ioe(-ct)

Through the use of equations 2 and equations 3 the Oxygen Saturation (SpO2) can be computed

from the output voltage. The results can be seen in Table 1.

(equation 2) R = ln(IMaxRed/IMinRed) / ln(IMaxIR/IMinIR)

(equation 3) SpO2 = [R*Ext(Hb IR) - Ext(Hb Red)] / [R*Ext(Hb IR) -

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

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Table 1

(Calculation of Oxygen Saturation from Voltage Output)

TRIAL Vmax REDVmin REDVmax 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 0.7846478

8 10.95948 10.883223 6.265075 6.24445 2.11749098 0.79173471

10 5.2234 5.128088 1.9704 1.934463 1.00048088 0.81817188

The next evaluation that was performed was intended to prove that the each

photodiode was successfully monitoring the appropriate light signals while filtering out

the other signal. This was proved by powering one LED and one photodiode at one time

and comparing the output. The results can be seen in Table 2 below. The fact that the

red photodiode only detected the red LED and the IR photodiode only detected the IR

LED proves that the photodiode effectively rejects unwanted signals.

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Table 2

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 PULSE

The device also needed to be consistent in its ratios of Max/Min voltage for bothred and infrared signals. The results are shown in Table 3 below. While the outputmagnitude varied slightly between tests, the ratios of maximum to minimum were verysimilar as can be seen by the small standard deviation throughout the tests.

Table 3

Proof of Consistency

Ratio Max/Min

Trial Red Infrared

A 1.019 0.98724

B 1.02 0.98337

C 0.962 0.99222

D 0.953 0.98657

E 0.971 0.98271

F 0.976 0.98157

Average 0.983 0.9856

St Dev 0.029 0.0039

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One last evaluation that was carried out was proving that the device actually

detects changes in blood oxygen saturation levels. A test was performed where oxygen

saturation levels were taken as a test subject held his breath, thus decreasing the oxygen

levels as time increased. The results can be seen in figure 11, where it is clear that

oxygen saturation levels decrease as time without oxygen increases.

Figure 11

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Chapter No. 3: Pulse Meter

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3.1 Introduction:

The human heart beats with an average rate of 70-80 times per minute. A finger

placed between an LED and LDR results in a voltage signal. This voltage signal is then

conditioned using high order filters and an amplifier to retrieve a signal of peak to peak 1

Volt amplitude. This signal is a sine wave. It is converted into a square wave by using a

comparator. The square wave is then passed through a pulse counter ( a programmed

micro controller) which gives as its output, the pulse rate f the subject under test.

3.2 Working Principle:

The portable pulse meter is useful for measuring the pulse of a person who istaking physical exercise such as running a marathon. The pulse of a person can bedetected by detecting a blood stream through a blood vessel. For detection of blood

stream a light source is so arranged as to project light onto a portion of the surface of theskin of a person to be examined. The projected light passes through the skin to impingeon a blood vessel to be reflected thereby, and a photoelectric element is so arranged as todetect the reflected light.

The intensity of the reflected light is different when the projected light hits ablood stream from when it does not. Therefore, by detecting the output produced by thephotoelectric element when it has detected the reflected light, it is possible to measure thepulse. Practically, the output signal from the photoelectric element caused by the lightreflected by blood stream is measured for a unit period of time.

A portable pulse meter is conveniently mounted on a finger of a hand of a personto be examined so that the instrument is not obstructive to physical exercise. To this end alight source and a photoelectric element are mounted on a detector plate, which may beworn by a finger of a hand of a person to be examined.

As can be easily understood from the above-mentioned principle of pulsemeasurement, the relative position between the detector plate having a light source and aphotoelectric element mounted thereon and the finger carrying the detector plate must befixed. Otherwise, the photoelectric element could not receive the light reflected by thesame portion of a blood vessel, and the amplitude of the output pulse from the elementwould fluctuate. Moreover, if the above-mentioned relative position is unstable, noise

would be produced so as to be superimposed on the output pulse of the photoelectricelement, so that it would be impossible to detect the pulse accurately.

The finger and the detector plate must always be kept in contact with each otherwith a constant pressure. If the pressure is too high, the detector plate squeezes the bloodvessel to stop the blood stream therethrough. If the pressure is too low, the relativeposition between the detector plate and the finger is likely to change.

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3.2.1 BlockDiagram

Accordingly, the primary object of the invention is to enable accurate detection ofthe pulse.

3.2.2 Signal Acquisition

A human finger is placed between a Light Emitting Diode and a Light Dependent

Resistor. There is a consequential change of voltage on the LDR. This voltage signal is

the basic signal that is further conditioned, processed and manipulated to generate the

Pulse Rate.

3.2.3 Signal Conditioning

The voltage signal on the LDR has a tremendous amount of noise, a DC

component of 7 Volts and unwanted frequencies up to 100 Hz. First of all, to block the

DC component, we pass the signal through a 10 C capacitor. The DC blocked signal is

then passed through a 4th order Low Pass Filter with a cutoff frequency of 30 Hz.

The filtered signal is again passed through a capacitor to further block any traces

of DC component. The resulting signal is a sign wave rising and falling with rate of heartbeat and its amplitude is 0.1 Volts. This signal passed through an amplifier with a gain of

10 to achieve a sine wave of peak to peak 1 Volt amplitude.The circuit developed for

signal conditioning is as follows:

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3.2.4 Signal Manipulation

A pulse counter can only count a square wave. Therefore the generated sine wave

is made into a square wave using a comparator that sets a high value for a specified

voltage range and sets a low value for the rest of the voltages. This square wave is then

read into a micro controller which is programmed to work as a counter. The counter

counts the number of high pulses in a minute and hence generate the pulse rate.

3.3 Circuit Components:

3.3.1 Red LEDs:

Like a normal diode, the LED consists of a chip of semiconducting materialimpregnated, or doped, with impurities to create a p-n junction. As in other diodes,current flows easily from the p-side, or anode, to the n-side, or cathode, but not in thereverse direction. Charge-carrierselectrons and holesflow into the junction fromelectrodes with different voltages. When an electron meets a hole, it falls into a lowerenergy level, and releases energy in the form of a photon.

The wavelength of the light emitted, and therefore its color, depends on the bandgap energy of the materials forming the p-n junction. In silicon or germanium diodes, theelectrons and holes recombine by a non-radioactive transition which produces no opticalemission, because these are indirect band gap materials. The materials used for the LED

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have a direct band gap with energies corresponding to near-infrared, visible or near-ultraviolet light.

We used Red LEDs as sensors for which light transmitted through the fingervaries with each surge of blood through the body with each heart beat. This variation

appears as varying voltage across the LDR (Light Dependent Resistor).

3.3.2 LD

RLDRs or Light Dependent Resistors are very useful especially in light/dark sensor

circuits. Normally the resistance of an LDR is very high, sometimes as high as 1000 000

ohms, but when they are illuminated with light resistance drops dramatically.

When the light level is low the resistance of the LDR is high. This prevents

current from flowing to the base of the transistors. Consequently the LED does not light.

However, when light shines onto the LDR its resistance falls and current flows into the

base of the first transistor and then the second transistor. The LED lights. The preset

resistor can be turned up or down to increase or decrease resistance, in this way it canmake the circuit more or less sensitive.

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3.3.3 Filters:

We have constructed 3rd order passive filter of cut off frequency 5 Hz in our

circuit.

Passive implementations of linear filters are based on combinations of resistors(R), inductors (L) and capacitors (C). These types are collectively known as passivefilters, because they do not depend upon an external power supply.

Inductors block high-frequency signals and conduct low-frequency signals, whilecapacitors do the reverse. A filter in which the signal passes through an inductor, or inwhich a capacitor provides a path to ground, presents less attenuation to low-frequencysignals than high-frequency signals and is a low-pass filter. If the signal passes through acapacitor, or has a path to ground through an inductor, then the filter presents lessattenuation to high-frequency signals than low-frequency signals and is a high-pass filter.Resistors on their own have no frequency-selective properties, but are added to inductorsand capacitors to determine the time-constants of the circuit, and therefore thefrequencies to which it responds.

The inductors and capacitors are the reactive elements of the filter. The number of

elements determines the order of the filter. In this context, an LC tuned circuit being usedin a band-pass or band-stop filter is considered a single element even though it consists oftwo components.

At high frequencies (above about 100 megahertz), sometimes the inductorsconsist of single loops or strips of sheet metal, and the capacitors consist of adjacentstrips of metal. These inductive or capacitive pieces of metal are called stubs.

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A low-pass electronic filter realised by an RC circuit:

The simplest passive filters consist of a single reactive element. These areconstructed of RC, RL, LC or RLC elements.

The quality or "Q" factor is a measure that is sometimes used to describe simpleband-pass or band-stop filters. A filter is said to have a high Q if it selects or rejects arange of frequencies that is narrow in comparison to the centre frequency. Q may bedefined for bandpass and band-reject filters as the ratio of centre frequency divided by3dB bandwidth. It is not commonly employed with higher order filters where otherparameters are of more concern, and for high-pass or low-pass filters Q is not normallyrelated to bandwidth.

3.3.4 Amplifiers:

Generally, an amplifier or simply amp, is any device that changes, usuallyincreases, the amplitude of a signal. The "signal" is usually voltage or current. The

relationship of the input to the output of an amplifier usually expressed as a functionof the input frequency is called the transfer function of the amplifier, and themagnitude of the transfer function is termed the gain.

The gain of an amplifier is the ratio of output to input power or amplitude, and isusually measured in decibels. (When measured in decibels it is logarithmically related tothe power ratio: G(dB)=10 log(Pout /(Pin)). RF amplifiers are often specified in terms ofthe maximum power gain obtainable, while the voltage gain of audio amplifiers and

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instrumentation amplifiers will be more often specified (since the amplifier's inputimpedance will often be much higher than the source impedance, and the load impedancehigher than the amplifier's output impedance).

The initial signal obtained from the LDR has a frequency range of 100 Hz, most

of which is noise. Since we only need to take into account around 1.2 Hz of the signal toextract the information about the human heart beat, we filter out of most of the noise by

using 3rd order passive filters at the required cut off frequency. The filtered signal gives a

voltage variation so small; to be able to detect it we must amplify it around 1000 times.

3.3.5 Capacitors:

Like a battery, a capacitor has two outside connections. Unlike a battery,however, the polarity of these connections is interchangeable. A battery always has one

side positive and the other side negative, and these symbols are permanently labeled onthe outside of the battery. A capacitor, however, can have either side be positive ornegative; The polarity is determined by how you charge the capacitor. If you hook up thecapacitor to a power source, the side connected to the positive side of the source willbecome positively charged, and the side connected to the negative side of the source willbecome negatively charged. The two leads from the capacitor are essentially symmetricalwhen the capacitor comes from the factory, and it can be charged whichever way youlike.

A capacitor's capacity is measured in capacitance. Capacitance is measured infarads (abbreviated F), named after Michael Faraday, the great chemist who invented the

capacitor in the 1800s. One farad (1F) is an uncommonly large amount of electricity forelectronics work, so in electronics you'll mostly see capacitance expressed in microfarads( F), nanofarads (nF), or picofarads (pF).

An interesting property of capacitors is that they will block DC after they becomecharged, but will (for the most part) allow AC to flow through. When a capacitor is fullydischarged, DC can flow through it freely, but as it is doing so, the cap is graduallybecoming charged. Finally, when it has reached its storage limit, the cap will not allowany more electricity to flow through it, and will act as a blocker on the circuit. This canbe observed if you simply wire a capacitor in series with a simple circuit connecting abattery to a light. When the circuit first comes on, the light will turn on, but after some

time (when the cap becomes fully charged) it will turn off. Exactly how long it takes thisto happen depends on the capacitance of the cap; with very low-capacitance caps, it willprobably happen faster than your eye can perceive, but it still will happen. If you removethe battery and simply leave the cap connected to the light, the light will turn on again asthe cap flows into itself, acting like a battery, and the light will stay on until the cap fullydischarges.

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DC blocking is must in the formation of the circuit of a pulse meter since thepulses cannot me counted unless the signal has been dc blocked and passed through acomparator to convert the sine wave into a square wave.

3.3.6 Display:

The display of the heart rate was done using a 7 segment digital displayprogrammed through a micro controller to display the heart rate in real time. The countercounts up pulse for every 10 seconds and cumulates the result in previous 10 secondsuntil 60 seconds. Then the previous 10 seconds are discarded and the next 10 seconds aretaken into account to calculate the heart rate. This way an accurate update continues.

3.3.6.1 Crude Circuit Diagram

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3.4 Features And Advantages of Pulse Meter:

y Used for continuous real time measurement of heart rate of patients

y Used to monitor the heart beat during anesthetic conditions

y Used to monitor heart rates while running/jogging/workouts

y

Portabley Inexpensive

y In-house manufactured

y Accuracy

y Real time measurements

3.5 Sources of Error in the Circuit:

y Very sensitive to light. If T-tube not properly sealed, major errors

y Frequency filtering and correct cut offsy Lack of proper DC Blocking

3.6 Ways of Overcoming Errors

y Use of non polar capacitors to reduce the noise generated from the presence of dc

component

y Use of greater than 10 k ohms while constructing the amplifiers at appropriate gain

y Ensuring movement protected input of signal i.e. well constructed T- Tube for finger

instruction.

y Ensuring light protected environment to improve the sensitivity and performance of

the circuit to generate appropriate results.

3.7 Conclusion:

Our current product is an accessible, transferable base product capable of

successfully detecting changes in hemoglobin light absorbance based on oxygen

saturation levels in humans and mice. It is also capable of detecting changes in SaO2

levels in humans. For future models in mice we predict that with more time and

possibly some slight modifications of our design, an accurate reading of a mouse's

saturated oxygen levels in its hemoglobin will be able to be performed.

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