JIMMA UNIVERSITY

JIMMA INSTITUTE OF TECHNOLOGY

SCHOOL OF BIOMEDICAL ENGINEERING

Project Tittle: Early Detection of Hepato-Biliary Disorder

FINAL REPORT

Author’s Name
Advisor’s Name:
1. Abdulferid Birhanu…………..0006/07
1. Solomon W/Tsadik
2. Abrham Bekele ………………0100/07
2. Washihun Alemayehu
3. Biruk Mulushewa……………..0426/07
4. Hafiz Abdulkerim……………..0842/07
5. NimonaKebede ………………0088/07
6. Mahlet Gashaw ……………….1109/07

Date: 13/06/2019
 EXECUTIVE SUMMARY
Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to
complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma.
Cirrhosis and liver cancer account for 3.5% of all deaths worldwide. Hepato-biliary disorders,
especially those related directly to liver, are chronic and undiagnosed until final stage. The poor
habit of taking routine check-up in our community makes the management of these disorders hard
and complex. Liver by its nature, don’t manifest its symptoms in the early stages of dysfunction
and late diagnosis makes may make the treatment plan ineffective and expensive to management
measures taken by physicians. Existing detection mechanisms are invasive, expensive, and non-
specific and require highly trained professionals to operate on and perform them. This project tries
to solve the problems associated with late diagnosis of patients with hepato-biliary disorders by
designing and developing cost effective device capable of identifying these disorders at their early
age without the aid of professionals.

Urinalysis is a method of studying different characteristics of urine and analyzing its parameters
in order to diagnose a patient. The developed device can accurately indicate the existence of
potential hepato-biliary disorders and classify them as hepatic, hemolytic or biliary obstruction by
Urinalysis (diagnosing a urine sample taken from the patient). It detects the presence and amount
of bilirubin and urobilinogen. Furthermore, to increase degree of certainty, the Specific Gravity of
the sample urine will also be measured. The design uses photometric properties of the mentioned
chemicals at different levels of concentration in a urine sample when they are subjected to specific
reagents that are prepared for them.

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 DECLARATION
We hereby declare that this report, submitted to the Biomedical Engineering Department at the
Jimma Institute of Technology as a partial fulfillment of the requirements for the degree of
Bachelor of Science in Biomedical Engineering, has not been submitted as exercise for a degree
at any other university. We also certify that the work described herein is entirely our own work
with the exception of paraphrased or quoted work whose source are appropriately cited in the
references.

This report may be made valuable within the university library and may be photocopied or loaned
to other libraries as a reference for others’ work.

Student’s Name Signature Date

1. Abdulferid Birhanu ---------------- --------------

2. Abraham Bekele --------------- --------------
3. Biruk Mulushewa -------------- --------------
4. Hafiz Abdulkerim -------------- --------------
5. Nimona Kebede -------------- --------------
6. Mahlet Gashaw --------------- --------------

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 STATEMENT OF APPROVAL
On behalf of the Department of Biomedical Engineering at the jimma Institute of Technology, We,
the mentors of this project, early detection of Hepato_biliary disorders, and we, the evaluator,
confirm that this project was approved as the topic for the final year project for the students,
Abdulferid Birhanu, Abrham Bekele, Biruk Mulushewa, Hafiz Abdulkerim, Nimona Kebede and
Mahlet Gashaw.

Mentors: Signature Date

1. Solomon W/tsadik ---------------- ----------------

2. Wasihun Alemayehu ------------------ ----------------

Evaluators: Signature Date

1. ---------------- ----------------
2. ---------------- ----------------

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 ACKNOWLEDGMENT
First and foremost, thanks to the God, the almighty, for his extensive blessings throughout our project work
to complete the project successfully.

We would like to express our deep and sincere gratitude to our advisors, Mr. Wasihun Alemayehu, MSC,
Head, School of Biomedical Engineering and Mr. Solomon W/Tsadik for providing invaluable guidance
throughout this project. They have taught us the methodology to carry out the project and to present the
final report as clearly as possible. It was a great privilege and honor to work and study on the project.
Therefore, we are extremely grateful for Jimma University, especially school of Biomedical Engineering.
We would like to extend our heartfelt thanks for Mrs. Yadeno Yazachew and other individuals who
supported the conduct of this project. In addition, to their friendship, empathy, and great sense of humor.
We are over helmed in all humbleness and gratefulness to acknowledge our depth to all those who have
helped us to put these ideas, well above the level of simplicity and into something concrete such as
Biomedical engineers in Arsho medical center and our clients.

Any attempt at any level cannot be satisfactorily completed without the support guidance of our parents
and friends. We would like to thank our friends and parents who helped us in gathering different
information, providing financial support, collecting data and guiding us from time to time in making this
project completed.

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Table of Contents
EXECUTIVE SUMMARY........................................................................................................................ I
Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to
complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis and
liver cancer account for 3.5% of all deaths worldwide. Hepato-biliary disorders, especially those related
directly to liver, are chronic and undiagnosed until final stage. The poor habit of taking routine check-up
in our community makes the management of these disorders hard and complex. Liver by its nature, don’t
manifest its symptoms in the early stages of dysfunction and late diagnosis makes may make the
treatment plan ineffective and expensive to management measures taken by physicians. Existing detection
mechanisms are invasive, expensive, and non-specific and require highly trained professionals to operate
on and perform them. This project tries to solve the problems associated with late diagnosis of patients
with hepato-biliary disorders by designing and developing cost effective device capable of identifying
these disorders at their early age without the aid of professionals. ............................................................... I
Urinalysis is a method of studying different characteristics of urine and analyzing its parameters in order
to diagnose a patient. The developed device can accurately indicate the existence of potential hepato-
biliary disorders and classify them as hepatic, hemolytic or biliary obstruction by Urinalysis (diagnosing a
urine sample taken from the patient). It detects the presence and amount of bilirubin and urobilinogen.
Furthermore, to increase degree of certainty, the Specific Gravity of the sample urine will also be
measured. The design uses photometric properties of the mentioned chemicals at different levels of
concentration in a urine sample when they are subjected to specific reagents that are prepared for them. ... I
DECLARATION ...................................................................................................................................... II
STATEMENT OF APPROVAL ............................................................................................................. III
ACKNOWLEDGMENT ......................................................................................................................... IV
CHAPER ONE .......................................................................................................................................... 1
1.1 Background and Clinical Significance ........................................................................................... 1
Liver failure is severe deterioration in liver function. It is caused by a disorder or substance that damages
the liver. Liver failure can result from many types of liver disorder, the most common is viral infections
including viral hepatitis, cirrhosis, inherited liver disorder, and liver damage from alcohol or drugs such
as acetaminophen. ....................................................................................................................................... 1
Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to
complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis and
liver cancer account for 3.5% of all deaths worldwide. About 2 billion people consume alcohol worldwide
and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated
liver disease. [3] .......................................................................................................................................... 1
According to WHO data published in 2017, Annually 14,213 people in Ethiopia lose their lives due to
hepato-biliary disorders. The number is likely to be growing year after year as researches indicate. [4] .... 2
1.1 The Liver Anatomy ......................................................................................................................... 2
1.2 Physiology of Liver ......................................................................................................................... 3

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 1.3 Symptoms ........................................................................................................................................ 4
1.4 Complications .................................................................................................................................. 5
1.4 Literature review ............................................................................................................................ 5
1.4.1 Liver function test: Clinical urine tests .................................................................................. 5
1.4.2 Clinical significance of urine bilirubin ................................................................................... 6
1.4.3 Clinical Significance of Urobilinogen in Urine: ..................................................................... 7
1.4.3 Measuring urine specific gravity ............................................................................................. 8
1.5 Existing Solutions ............................................................................................................................ 8
1.5.1 Urine dipstick test .................................................................................................................... 8
Urine dipstick methodology ............................................................................................................. 1
1.5.2 Blood test .................................................................................................................................. 1
1.2.2 Liver biopsy .............................................................................................................................. 2
1.2.3 Ultrasound and X-ray machines ............................................................................................. 2
1.6 Preliminary Gap Analysis .............................................................................................................. 3
1.7 Project Mission ................................................................................................................................ 4
1.4.1 Problem Statement ................................................................................................................... 4
1.4.2 Need Statement......................................................................................................................... 4
1.4.3 Team Mission ........................................................................................................................... 4
1.8 Objectives and Constraints ............................................................................................................ 4
1.8.1 General objectives .................................................................................................................... 4
1.8.2 Specific objectives .................................................................................................................... 4
1.8.2 Constraints ............................................................................................................................... 5
CHAPTER TWO ...................................................................................................................................... 6
DESIGN STRATEGY .............................................................................................................................. 6
2.1 Background information ................................................................................................................ 6
2.2 Design approach .............................................................................................................................. 6
2.3 Brainstorming session ..................................................................................................................... 6
2.4 Evaluation of brainstormed idea.................................................................................................... 9
2.4.1 Creating awareness among the society ................................................................................... 9
2.4.2 Increasing number of physicians: ........................................................................................... 9
2.4.3 Device for gross examination ................................................................................................. 10
2.4.4 Device for blood sample test .................................................................................................. 10
2.4.5 Device for liver biopsy test ..................................................................................................... 11

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 2.4.6 Device for urine sample test .................................................................................................. 12
2.5 Concept screening Pugh matrix ................................................................................................... 13
2.6 Pugh matrix for the alternatives .................................................................................................. 13
2.7 Proposed solution .......................................................................................................................... 14
2.8 Component list and Discussion .................................................................................................... 15
2.8.1 Super LEDs ............................................................................................................................ 15
2.8.2 Heat-Sync................................................................................................................................ 15
2.8.3 Photodiode: ............................................................................................................................. 16
2.6.4 Light emitting diode ............................................................................................................... 16
2.8.4 Cuvette .................................................................................................................................... 17
2.9 Device implementation plan ......................................................................................................... 17
CHAPTER THREE ................................................................................................................................ 18
FINAL DESIGN...................................................................................................................................... 18
4.1 Implementation Design ................................................................................................................. 18
3.2 Design changes .............................................................................................................................. 19
3.2.1 Measurement change ............................................................................................................. 19
3.2.2 Parameter added .................................................................................................................... 19
3.2.3 Parameters removed .............................................................................................................. 20
3.3 Construction of prototype ............................................................................................................ 20
3.3.1 Initial prototype...................................................................................................................... 20
3.3.2 Second prototype .................................................................................................................... 20
3.3.3 Third prototype ...................................................................................................................... 21
3.3.4 Fourth prototype .................................................................................................................... 22
3.4 Final component lists .................................................................................................................... 23
3.5 Outcome of the project ................................................................................................................. 23
CHAPTER FOUR................................................................................................................................... 24
TEST AND RESULT.............................................................................................................................. 24
4.1 Design Criteria .............................................................................................................................. 24
4.1.1 Accuracy ................................................................................................................................. 24
4.1.2 Durability ................................................................................................................................ 24
4.1.3 Easy to Use .............................................................................................................................. 24
4.1.4 Portability ............................................................................................................................... 24
4.1.5 Cost ......................................................................................................................................... 25

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 4.2 Testing............................................................................................................................................ 25
4.2.1 Test for Accuracy ................................................................................................................... 25
4.3 Test conducted............................................................................................................................... 26
CHAPTER FIVE .................................................................................................................................... 29
SUMMARY AND RECOMMENDATION .......................................................................................... 29
REFERENCE.......................................................................................................................................... 30
APPENDICES ......................................................................................................................................... 32
Appendix A .......................................................................................................................................... 32
Appendix B .......................................................................................................................................... 35
A. Arduino Mega.......................................................................................................................... 35
Appendix D .......................................................................................................................................... 37
Appendix E .......................................................................................................................................... 39
Appendix F .......................................................................................................................................... 42
APPENDIX G ....................................................................................................................................... 47
ACRONYMS........................................................................................................................................ 47

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LIST OF FIGURES

Figure 1.1 Liver anatomy ................................................................................................................ 3

Figure 1.2 Liver physiology ............................................................................................................ 4
Figure 1. 3 Liver dipstick test ......................................................................................................... 1
Figure 2.1 Brainstorming idea ........................................................................................................ 8
Figure 2.2 Flow chart of gross examination ................................................................................. 10
Figure 2.3 Flow chart of blood sample test................................................................................... 11
Figure2.4 Flow chart for liver biopsy test ..................................................................................... 11
Figure 2.5 Flow chart for urine test ................................................................................................ 4
Figure2.6 Flow chart of diagnosis system .................................................................................... 15
Figure 2.7 Super LED ................................................................................................................... 15
Figure2.8 Heat sync ...................................................................................................................... 16
Figure2.9 Photodiode .................................................................................................................... 16
Figure2.10 LED ............................................................................................................................ 16
Figure2.11 Cuvette ........................................................................................................................ 17
Figure 3.1Implementation design flow chart ................................................................................ 19
Figure 3.2 Initial prototype ........................................................................................................... 20
Figure 3.3 Prototype mock-up ...................................................................................................... 21
Figure 3.4 Third prototype using can ............................................................................................ 21
Figure 3.5 Fourth prototype to display condition of liver diseases............................................... 22
Figure 5.1 while performing test ................................................................................................... 27
Figure 5 .2 Different conditions of hepato-biliary disorder .......................................................... 28
Figure 6.1 Arduino mega .............................................................................................................. 35
Figure 6.2 LCD ............................................................................................................................. 36
Figure 6.3 Other components........................................................................................................ 36
Figure 6.4 V-I characteristics of photodiode ................................................................................ 38

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LIST OF TABLES
Table 1.1 Clinical significant test results: ....................................................................................... 7
Table 2.1 Concept screening Pugh matrix .................................................................................... 13
Table 2.2Pugh matrix for alternatives ........................................................................................... 13
Table 4.1 Test conducted and evaluated ....................................................................................... 26

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 CHAPER ONE
1.1 Background and Clinical Significance

Liver failure is severe deterioration in liver function. It is caused by a disorder or substance that
damages the liver. Liver failure can result from many types of liver disorder, the most common is
viral infections including viral hepatitis, cirrhosis, inherited liver disorder, and liver damage from
alcohol or drugs such as acetaminophen.

Viral hepatitis is the most common causes of liver infection which inflames the liver. Hepatitis A
is caused by eating or drinking something that is tinted by fecal matter. It usually goes away by
itself within 6 months without long term harm. Hepatitis B is acquired from somebody else, such
as through unprotected sex or taking drugs with shared needles. If it lasts longer than 6 months, it
is more likely to cause liver cancer. Hepatitis C is caused by infected blood that gets into blood.
Symptoms may not show up for many years. Health care professionals are risk to hepatitis C. Auto
immune hepatitis, Primary sclerosing cholangitis, which scars the bile ducts, and Liver cancer,
which is called as hepatocellular carcinoma, is more likely occurred due to hepatitis or cirrhosis.
It affects women more often than men, and African-Americans more often than whites. [1]

A large portion of the liver must be damaged before liver failure occurs. Liver failure may develop
rapidly over days or weeks or gradually over months or years .In acute liver failure, people may
go from being healthy to near death within a few days. In chronic liver failure, the deterioration in
health may be very gradual until a dramatic event, such as vomiting blood or having bloody stools,
occurs. Blood in vomit or stool is usually caused by bleeding from varicose veins in the esophagus
and stomach. Ultimately, liver failure is fatal if it is not treated or if the liver disorder is progressive.
Even after treatment, liver failure may be irreversible. Some people die of kidney failure. Some
people develop liver cancer. [2]

Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to
complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma.
Cirrhosis and liver cancer account for 3.5% of all deaths worldwide. About 2 billion people

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consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders
and are at risk of alcohol-associated liver disease. [3]

According to WHO data published in 2017, Annually 14,213 people in Ethiopia lose their lives
due to hepato-biliary disorders. The number is likely to be growing year after year as researches
indicate. [4]

1.1 The Liver Anatomy

The liver is second largest internal organ in the human body, which is located in the right upper
quadrant of the abdomen, beneath the diaphragm, and is protected by the lower right ribs. It also
extends across the midline toward the left upper quadrant of the abdomen. As it becomes enlarged,
the liver will grow further across the upper abdomen and down towards the navel. The liver is
divided into two lobes and has a rich blood supply obtained from two sources; 1) the portal vein
delivers blood from the gastrointestinal tract (stomach, intestine, and colon) and spleen, and 2) the
hepatic artery supplies blood from the heart.

Its domed upper surface relates entirely to the diaphragm while its postero-inferior, or visceral,
surface rests against the abdominal esophagus, stomach, upper duodenum, hepatic flexure of the
colon, right kidney and suprarenal gland, as well as carrying the gall bladder. Its surface relations
can be marked out by joining points on the right costal margin in the mid-axillary line, (the 10th
rib), the right 5th intercostal space ditto and the left 5th intercostal space in the mid-clavicle line.
[5]

The biliary tree describes a system of tubes that collect bile, used to help digest food, and drains it
into the gallbladder or the intestine. Intrahepatic ducts are located inside the liver while extra-
hepatic ducts are located outside the liver. [6]

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 Figure 1.1 Liver anatomy

1.2 Physiology of Liver

The liver comprises around 2% of an adult’s body weight. The functional unit of the liver is the
lobule. It is hexagonal and has a portal vein, hepatic artery and bile duct to each corner. The
foundation of the lobule is composed of hepatocytes, which have physiologically distinct apical
and basolateral membranes.

Hepatocytes are responsible for making many of the proteins in the body that are required for many
functions, including blood clotting factors, and albumin, required to maintain fluid within the
circulation system. The liver is also responsible for manufacturing cholesterol and triglycerides.
Carbohydrates are also produced in the liver and the organ is responsible for turning glucose into
glycogen that can be stored both in the liver and in the muscle cells. The liver also makes bile that
helps with food digestion. [7]

The liver has multiple functions. It makes many of the chemicals required by the body to function
normally. The liver plays a role in nearly every organ system in the body. It interacts with the
endocrine and gastrointestinal system by aiding in digestion and metabolism. It is the storage
location for fat soluble vitamins and handles cholesterol homeostasis. It plays a role in hematology
with clotting factor and protein synthesis. The liver plays a role in RBCs breakdown into
unconjugated bilirubin and conjugates. It plays a role in sex hormone metabolism and produces
carrier proteins which are important in reproduction and development.

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The liver helps in detoxifying the body by converting ammonia, a byproduct of metabolism in the
body, into urea that is excreted in the urine by the kidneys. The liver also breaks down medications
and drugs, including alcohol, and is responsible for breaking down insulin and other hormones in
the body. The liver also stores vitamins and chemicals that the body requires as building blocks.
[6]

Figure 1.2 Liver physiology

1.3 Symptoms

People with liver failure usually have jaundice, ascites, hepatic encephalopathy, and generally
failing health. Jaundice makes the skin and whites of the eyes look yellow. Ascites may cause the
abdomen to swell. Hepatic encephalopathy may cause confusion or drowsiness.

Most people also have general symptoms, such as fatigue, weakness, nausea, and loss of appetite
and the breath may have a musty sweet odor. People may bruise and bleed easily. For example,
bleeding from a small cut or a nosebleed may not stop on its own and may even be difficult Loss
of blood can result in low blood pressure also called, hypotension and shock.

In acute liver failure, people may go from being healthy to near death within a few days. In chronic
liver failure, the deterioration in health may be very gradual until a dramatic event, such as
vomiting blood or having bloody stools, occurs. Blood in vomit or stool is usually caused by
bleeding from varicose veins in the esophagus and stomach. [8]

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1.4 Complications

Many effects occur because the liver malfunctions:

 The liver can no longer adequately process bilirubin so that it can be eliminated from the
body. Bilirubin then builds up in the blood and is deposited in the skin that results in
jaundice.
 The liver can no longer synthesize enough of the proteins that help blood clot. The result
is a tendency to bruise and bleed, which is called coagulopathy.
 Blood pressure in the veins that bring blood from the intestine to the liver is often
abnormally high, which is called portal hypertension.
 Fluid may accumulate within the abdomen.
 Brain function may deteriorate because the liver cannot remove toxic substances as it
normally does and these substances build up in the blood. This disorder is called hepatic
encephalopathy.
 New veins called collateral vessels that bypass the liver may form. They often form in the
esophagus and the stomach. There, the veins enlarge and become twisted. These veins
called varicose veins of the esophagus or esophageal varices or stomach gastric varices are
fragile and prone to bleeding.
 Liver failure may lead to kidney failure that is called hepatorenal syndrome.
 People may have metabolic abnormalities, such as a low potassium level in the blood
hypokalemia or a low blood sugar level hypoglycemia.[2]

1.4 Literature review

1.4.1 Liver function test: Clinical urine tests

Urine is an aqueous solution of greater than 95% water, with a minimum of these remaining
constituents, in order of decreasing concentration:

 Urea 9.3 g/L.

 Chloride 1.87 g/L.
 Sodium 1.17 g/L.
 Potassium 0.750 g/L.

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  Creatinine 0.670 g/L.
 Other dissolved ions, inorganic and organic compounds (proteins, hormones, metabolites).

Urine is sterile until it reaches the urethra, where epithelial cells lining the urethra are colonized
by facultative anaerobic gram-negative rods and cocci. Urea is essentially a processed form of
ammonia that is non-toxic to mammals, unlike ammonia, which can be highly toxic. It is processed
from ammonia and carbon dioxide in the liver. [9]

Clinical urine tests are various tests of urine for diagnostic purposes. The most common is a
urinalysis (UA), one of the most common methods of medical diagnosis. The word is a
portmanteau of the words urine and analysis. Other tests are urine culture (a microbiological
culture of urine) and urine electrolyte levels. The target parameters that can be measured or
quantified in urinalysis include naked-eye (gross) examination for color and smell plus analysis
for many substances and cells, as well as other properties, such as specific gravity. A part of a
urinalysis can be performed by using urine test strips, in which the test results can be read as color
changes. Another method is light microscopy of urine samples. [10]

The consistency, odor, and color of urine are often indicators of lifestyle and health condition. In
some cases, orange urine can indicate a problem with your liver or bile duct, especially if light-
colored stools are observed. In addition, some liver and kidney disorders can turn urine dark brown,
as can some urinary tract infections. Most of the time, urine does not have a strong smell for a
healthy person. The smell of urine usually is not such a direct indicator of a disease, but it can be
used as indication of abnormality along with other parameters. Musty smell usually indicates
potential liver disease and certain metabolic disorders. [11]

1.4.2 Clinical significance of urine bilirubin

A bilirubin in urine test measures the levels of bilirubin in urine. Bilirubin is a yellowish substance
made during the body's normal process of breaking down red blood cells. Bilirubin is found in
bile, a fluid in your liver that helps you digest food. If your liver is healthy, it will remove most of
the bilirubin from body. If liver is damaged, bilirubin can leak into the blood and urine. Bilirubin
in urine may be a sign of liver disease.

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Only the conjugated form of bilirubin appears in urine. Conjugated bilirubin can appear in the
urine when bile ducts are obstructed or when the integrity of the liver is compromised. Therefore,
urine bilirubin reflects increased levels of conjugated bilirubin in the serum. The presence of
bilirubin in human urine is consistent with hepatitis, cirrhosis, gall bladder disease, and various
hepatocellular cancers. Urine bilirubin levels are commonly assessed with the urinalysis dipstick
test; this test involves use of a pad that produces a diazotization color reaction in the presence of
bilirubin. Urine bilirubin testing became common when a colorimetric bilirubin test pad was
included in common urinalysis test strips. The goal of urine bilirubin screening is to potentially
reveal a pathologic liver or gall bladder condition early, before jaundice is apparent. [12]

1.4.3 Clinical Significance of Urobilinogen in Urine:

Urobilinogen is a colorless by-product of bilirubin reduction. It is formed in the intestines by

bacterial action on bilirubin. About half of the urobilinogen formed is reabsorbed and taken up via
the portal vein to the liver, enters circulation and is excreted by the kidney. In liver disease, the
intrahepatic urobilinogen cycle is inhibited also increasing urobilinogen levels. Urobilinogen is
converted to the yellow pigmented urobilin apparent in urine. Urinary urobilinogen may be
increased in the presence of a hemolytic process such as hemolytic anemia. It may also be
increased with infectious hepatitis, or with cirrhosis.

Comparing the urinary bilirubin result with the urobilinogen result may assist in distinguishing
between red cell hemolysis, hepatic disease, and biliary obstruction.

Table 1.1 Clinical significant test results:

Condition Urine bilirubin result Urine urobilinogen result

Hemolytic disease Negative Increased

Hepatitic disease Positive or Negative Increased

Biliary obstruction Positive Normal

The test for urobilinogen is based on the ehrlich reaction. P-dimethylaminobenzaldehyde in an

acid medium with a color enhancer reacts with urobilinogen to form a pink-red color. The urine

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reagent strip reactivity increases with increasing temperature. The optimum temperature for testing
is 22-260 C. A freshly voided sample should be tested to ensure optimal result. [13]

1.4.3 Measuring urine specific gravity

The specific gravity (SG) of urine signifies the concentration of dissolved solutes and reflects the
effectiveness of the renal tubules to concentrate it when the body needs to conserve fld. If there
were no solutes present the urines SG would be 1.000, the same as pure water. The SG of urine is
around 1.010 but can vary greatly. Decreased SG may be due to excessive fluid intake (oral or IV
fluids), renal failure, acute glomerulonephritis, pyelonephritis, acute tubular necrosis and diabetes
insipidus. Increased SG may be due to: dehydration due to poor fluid intake, vomiting or diarrhea,
heart failure, liver failure, inappropriate antidiuretic hormone secretion, it also reflects a high
solute concentration, which may be from glucose (diabetes or IV glucose) or protein. [11]

Urine solution with more acidic concentration manifests the presence of H+ ions, interaction of
H+ ions with the chemical reagent bromothymol blue changes color of urine to dark green. The
change in color, show up, the presence of higher specific gravity in urine solution.[14]

1.5 Existing Solutions

Currently many kinds of liver function tests are available which use various testing mechanisms
and samples. Most often, diseases of the liver can be diagnosed by taking history, physical
examination, and blood tests. On occasion, should the diagnosis be unclear or to assess the degree
of damage to the liver, a liver biopsy may be necessary.

1.5.1 Urine dipstick test

Urine dipstick test is a microscopic examination of spun urinary sediment. It is rapid and semi
quantitive assessment of urinary characteristics. The dipstick test uses a thin plastic strip treated
with chemicals. It is dipped into urine, and the chemicals on the stick react and change color if
levels are above abnormal. The dipstick test checks for:

 PH  Glucose
 Protein  Ketones

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  Blood  Nitrites
 Urobilinogen  Leukocyte esterase, and
 Bilirubin  Specific gravity

Urine dipstick methodology

 Paper tabs impregnated with chemical reagents
 Reagents are chromogenic
 Reagents are time developed
 Some reaction are highly specific
 Other are sensitive to the presence of interfering substances or extremes of PH. [15]

Figure 1. 3 Liver dipstick test

1.5.2 Blood test

A series of special blood tests can often determine whether the liver is functioning properly or not.
These tests can also distinguish between acute and chronic liver disorders and between hepatitis
and cholestasis

The most commonly performed blood tests include the following:

 Serum bilirubin test: This test measures the levels of bilirubin in the blood. Elevated levels
of bilirubin may indicate an obstruction of bile flow or a problem in the processing of bile
by the liver.

 Serum albumin test: This test is used to measure the level of albumin (a protein in the
blood) and aides in the diagnosis of liver disease.

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  Serum alkaline phosphatase test: This test is used to measure the level of alkaline
phosphatase (an enzyme) in the blood. Alkaline phosphatase is found in many tissues, with
the highest concentrations in the liver, biliary tract, and bone. This test may be performed
to assess liver functioning and to detect liver lesions that may cause biliary obstruction,
such as tumors or abscesses.

 Prothrombin time (PTT) test: The prothrombin time test measures how long it takes for
blood to clot. Blood clotting requires vitamin K and a protein that is made by the liver.
Prolonged clotting may indicate liver disease or other deficiencies in specific clotting
factors.

 Alanine transaminase (ALT) test: This test measures the level of alanine aminotransferase
(an enzyme found predominantly in the liver) that is released into the bloodstream after
acute liver cell damage. This test may be performed to assess liver function, and/or to
evaluate treatment of acute liver disease, such as hepatitis.

 Aspartate transaminase (AST) test: This test measures the level of aspartate transaminase
(an enzyme that is found in the liver, kidneys, pancreas, heart, skeletal muscle, and red
blood cells) that is released into the bloodstream after liver or heart problems.

 Gamma-glutamyltranspeptidase test: This test measures the level of gamma-

glutamyltranspeptidase (an enzyme that is produced in the liver, pancreas, and biliary
tract). This test is often performed to assess liver function, to provide information about
liver diseases, and to detect alcohol ingestion.

 Lactic dehydrogenase test: This test can detect tissue damage and aides in the diagnosis of
liver disease. Lactic dehydrogenase is a type of protein (also called an isoenzyme) that is
involved in the body's metabolic process.

 5'-nucleotidase test: This test measures the levels of 5'- nucleotidase (an enzyme specific
to the liver). The 5'- nucleotidase level is elevated in persons with liver diseases, especially
those diseases associated with cholestasis (disruption in the formation of, or obstruction in
the flow of bile).

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  Alpha-fetoprotein test: Alpha-fetoprotein (a specific blood protein) is produced by fetal
tissue and by tumors. This test may be performed to monitor the effectiveness of therapy
in certain cancers, such as hepatomas.

 Mitochondrial antibodies test: The presence of these antibodies can indicate primary biliary
cirrhosis, chronic active hepatitis, and certain other autoimmune disorders. [16]

All the above mentioned clinical liver function tests require blood samples that need to be analyzed
by a skilled professional using expensive and complex medical devices like Chemistry machine.
Moreover, they all use invasive procedure for taking blood samples, which makes all of them
difficult to be performed solely by the patients themselves at their own residence.

1.2.2 Liver biopsy

A gastroenterologist or hepatologist or an interventional radiologist will insert a very fine needle
through the skin and into the liver, to retrieve a small bit of tissue. This can then be examined
under the microscope by a pathologist to help make the diagnosis. This procedure is done under
sterile conditions to prevent infection, and a local anesthetic is injected into the skin to decrease
the potential for pain. [17]

1.2.3 Ultrasound and X-ray machines

Ultrasound and chest X-ray are sometimes used as a screening tool for liver related disorders. They
possess a great deal of screening choice but they are way expensive and not helping with the poor
regular check-up habit; not to mention the requirement of skilled professionals and radiation risk
associated with the later one.

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1.6 Preliminary Gap Analysis
All the above mentioned clinical liver function tests require blood samples that need to be analyzed
by a skilled professional using expensive and complex medical devices like Chemistry machine.
Moreover, they all use invasive procedure (for taking blood samples), which makes all of them
difficult to be performed solely by the patients themselves at their own residence.

It is difficult to interpret Urine dipstick test results for individuals. False positive results might be
occurred and the result is affected by environmental factors such as: temperature and humidity.
Dipstick test only test for the certain chemicals in urine not their measured value.

Most of the time, failure of management measures taken by physicians and health professionals,
for the treatment of liver diseases, is due to the complications of the disorders on the late stages
that makes the treatment hard and impossible sometimes.

The main cause for late diagnosis is that, since patients are not alerted at the early stages, they have
no idea that they are getting sick. This is because our society has a poor habit of taking regular
health check-ups. Patients see their doctors only when they find out there is something that does
not feel right with their health status. Unfortunately, the main problem with liver failure is that
Liver by its nature, do not manifest its symptoms in the early stages of dysfunction and late
diagnosis makes the management of the disease very difficult and costly. Furthermore, The Liver
Functionality Tests are not as such available as they should be. In fact, Patients are expected to
visit higher health institutions and overpriced Private diagnosis centers in order to check their
health conditions related to liver disease.

The procedures for diagnosis and confirmation of hepato-biliary disorders require a highly trained
medical professionals and they are invasive, which requires blood samples and sometimes a small
tissue is taken for liver biopsy procedures, beside gross examinations.

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1.7 Project Mission
1.4.1 Problem Statement
The poor habit of our community for regular health check-ups makes it difficult to manage hepato-
biliary complications after late diagnosis. The liver function tests are only available at higher health
institutions and since the tests mainly use blood samples, it is difficult to adopt the testing
mechanisms into a household device that can detect liver disorders at early stages.

1.4.2 Need Statement

There is a need for a device that can detect potential presence of hepato-biliary disorders at early
stages, which can make the management measurements taken, much simpler and efficient.

1.4.3 Team Mission

The general mission of the project team is to minimize the deaths due hepato-biliary disorders and
improve the health status of the society by developing a device, which can assist in early detection
of the disorders. In addition, the team aims to provide a device, which can be used as a regular
screening mechanism that can alert the users about their liver related health conditions so that they
would know their status and take appropriate actions by consulting health professionals.

1.8 Objectives and Constraints

1.8.1 General objectives
 To develop a design that helps for early diagnosis of hepato-biliary disorders, Minimizing
management complications and deaths due late diagnosis of hepato-biliary disorders

1.8.2 Specific objectives

To design a device:
 Completely non-invasive prototype requiring no blood sample.
 Easy to operate and be available in each and every home
 Improving the habit of routine liver function check-ups.
 Providing easy, convenient, cheap and accurate means of diagnosis for hepato-biliary
disorders at home and health center.
 Study the anatomy and physiology of liver
 Study the characteristics of urine, bilirubin, urobilinogen and specific gravity
 Study the characteristics of photodiode

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1.8.2 Constraints
The absolute requirements from the device are:

 Portability- the device have to be movable, light enough to carry it around and small
enough not to hold huge space.
 Easy to use- the user should not find it hard to use the device. Apparently, the device has
to be easy to learn in just single training.
 Affordability- the device has to be a one-time purchase and not expensive.
 Self-use- the user should use the device alone with no professional help.
 Easy to adjust and maintain- the device has to be easily installed and easily maintainable
while failure.
 Accuracy- the device has to be in minimum of 95% exactness when it comes to detecting
the presence of hepato-biliary disorders.
 Effectiveness- the device must effectively differentiate liver related disorders from other
diseases in order to avoid generation of false positive results. Maximum of 5% false
positive result.
 Safety- the device should not bring any chemical, biological, electrical or psychological
harm to the user.

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 CHAPTER TWO
DESIGN STRATEGY
2.1 Background information
The most common Liver function tests are blood tests used to help diagnose and monitor liver
disease or damage. The test measures the levels of certain enzymes and proteins in blood. Blood
tests check for liver damage, and can help diagnose liver disease such as hepatitis and cirrhosis.
Currently, liver function tests may be adapted as part of a regular checkup or when having
symptoms of liver disease. The blood sample for liver function tests is usually taken from a vein
in the arm. The main risk associated with blood tests is soreness or bruising at the site of the blood
draw. To reduce risks associated with soreness of skin, urine test can be used as liver function test
which is more Comfortable and safe than blood test. The new design approach takes urine sample
form the user and test for the presence of bilirubin, urobilinogen and specific gravity.

2.2 Design approach

The design objective is to improve the health status of the society by developing a device, which
can assist in early detection of hepato-billiary disorders. The main goal of the design is to provide
an early self-assisted liver function test device. Urine sample is taken from the individual to be
examined in a sample holder or cuvette. In this case, three cuvettes are required to test the presence
of bilirubin, urobilinogen and specific gravity in urine. Each urine sample is then mixed with
appropriate reagents that can bring color change. Then it will be exposed to white, red and green
light emitting sources to examine for the presence of bilirubin, urobilinogen and measure specific
gravity respectively. Intensity of light passing through the sample is measured by photo detector.
The device can be used or deliver service either at home or in hospitals.

2.3 Brainstorming session

Brainstorming session is a program in which participants with different disciplines use their
collective power to bring forward a large number or more innovative ideas than an individual can
generate. Brainstorming session brings innovative ideas if members differ judgment, encourage
wild ideas, build on the idea of others, go for quantity, one conversation at a time, stay focused on
the topic and be visual. Since every participant should at least have some approximate knowledge
about the problem. Having many participants help to develop and raise ideas from different
perspectives, background and expertise.
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During brainstorming, Apart from solution ideas generated from members of the team, the session
involved physicians, who are working at JUSH, Biomedical engineers from Arsho medical center
and other healthcare organizations and advisors of the project and cooperative lectures.

The physicians provided detail clinical background on hepatic and biliary disorder, severity of the
disease, recent detection mechanisms, psychological impact on patients if late-diagnose.
Biomedical professionals forwarded technical support on the solution idea.

After brainstorming, concept screening followed which involves comparing all of the ideas against
the defined need specification to evaluate how well they satisfy the need. This process also
involves organizing the ideas into related groups to identify potential gaps or biases in the proposed
solutions, as well as opportunities to combine ideas into unique, synergistic solutions that better
address the need than any individual concept. If significant gaps are found or certain biases are
discovered that unnecessarily constrain the solutions, additional brainstorming may be required.
The final output of concept screening is a few concepts with which to begin the in depth concept
selection phases of the bio-design innovation process.

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 Figure 2.1 Brainstorming ideas

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2.4 Evaluation of brainstormed idea
During brainstorming, different design solutions were generated to overcome the identified
problem in both preventive and diagnosis ways. Preventive ways can reduce the occurrence of the
disease. Among the preventive ways;

 Developing Gross examination software.

 Increasing number of physicians in health institution.

 Creating awareness.

Possible solutions to detect hepato-biliary disorders:

 To design a device for blood sample test.

 To design a device for liver biopsy test.

 To design a device that can analysis urine sample.

2.4.1 Creating awareness among the society

In developing countries, the risk of hepatic disease increases as a result of poor regular health
checkup. Because liver disease does not manifest symptoms as the early stage, late diagnosis
makes the disease complicated and alleviate the proportion to death. Therefore, a planned course
of training on hepatic and associated biliary obstructions should be provided for the society.

Limitations:

 Some individual member of the society are not willing to take checkups even after
trainings.
 Financial problems

2.4.2 Increasing number of physicians:

As a conducted investigated in Ethiopian, physicians who works on hepatic disease and conduct
liver function are small in number. Increasing their number helps to provide accurate and on time
diagnosis to the patient.
Limitation:

 Increasing physicians’ is not totally curing if the disease reaches last stage.

2.4.3 Device for gross examination

This solution proposes software, which accepts the symptoms of the user as input parameters and
analyzes them in order to provide a useful suggestion for the user about their liver condition. This
solution is much easier than the first one to use, safer and less expensive but when it comes to
accuracy, reliability and effectiveness, it does not seem quite selectable.

Limitations: The system requires users to input symptoms of the disease, users should identify the
symptom clear.

The device accepts

input from the user

Inputs are analyzed

and interprated

Results are displayed

for the user

Figure 2.2 Flowchart for gross examination

2.4.4 Device for blood sample test

Blood test is used to determine whether a liver is functioning or not. Among the most commonly used blood
tests serum albumin and serum tests measure levels of bilirubin and albumin in the patient. Elevated level
of bilirubin may indicate an obstruction of bile flow and complications in the processing of bile by the liver.
Blood tests are used in diagnosis of liver disease. However, blood samples must be analyzed by trained
medical professionals and using expensive medical equipment such as blood chemistry analyzer and Blood
is acquired through incision of small needle into the patient.

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 Figure 2.3 Flow chart for blood sample test

2.4.5 Device for liver biopsy test

A liver biopsy is a procedure to remove a small piece of liver tissue, it can be examined under a microscope.
A liver biopsy is also used to determine the severity of liver disease. It is also commonly performed to help
diagnose certain liver disease such as chronic hepatitis B or C, Alcoholic liver disease and biliary cirrhosis.
However, the test uses invasive technique that induces pain at the biopsy site, bleeding, infection and
accidental incident to nearby organ.

Figure 2.4 Flow chart for liver biopsy test

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2.4.6 Device for urine sample test
This method is one of the viable solutions as the symptoms of hepato-biliary disorders manifest
their symptoms by altering the characteristics of urine. The analysis of urine characteristics is used
as an indication of the presence of liver related disorders in the patient. The device detects color
and odor of urine, measures the specific gravity of the urine sample, the presence of urobilinogen
and the presence of bilirubin in the patient’s urine so that it will effectively avoid false positive
results and alert the patient about his/her liver condition early.

Figure 2.5 Flow chart for urine test

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2.5 Concept screening Pugh matrix
The team has gone through screening the generated ideas by preparing a Pugh matrix containing
six decision criteria according to the need of the design.

Table 2.1 Concept screening Pugh matrix

Objectives Safety Affordability Efficiency Easy to Durability Portability Total
access
Safety X 1 0.75 1 1 1 4.75
Affordability 0 X 0 0.5 0.25 0.75 1.5
Efficiency 0.25 1 X 1 1 1 4.25
Easy to 0 0.5 0 X 0.5 0.75 4.75
access
Durability 0 0.75 0 0.5 X 0.75 2.00
Portability 0 0.25 0 0.25 0.25 X 0.75

Based on the screening objectives listed above, safety is the primary constraint to be considered further in
the design process.

2.6 Pugh matrix for the alternatives

The above objective’s weight screening calculation was applied to select the best solution from
the list of the proposed design.

Rank: 4-Best; 3-Good; 2-Sufficient; 1-Worst

Table 2.2 Pugh matrix for alternatives

Objectives Weight Urine analysis Blood sample Gross- Liver biopsy

analysis examination test
software
Safety 0.3167 3.5 1.10845 1 0.3157 3.5 1.10845 2 0.6334
Effectiveness 0.2834 3 0.08502 4 1.1336 1 0.2834 2 0.5668
Durability 0.1334 2 0.2668 1 1.1334 3 0.4002 4 0.5336
Easy to use 0.1167 4 0.4668 1 0.1167 3 0.3001 2 0.2334
Affordability 0.10 3 0.3 2 0.2 4 0.4 1 0.1
Portability 0.05 2 0.1 1 0.05 4 0.2 3 0.15
Total 1.0002 3.09225 1.9504 2.74215 2.22172

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According to the scoring computed among alternative solutions prescreening liver disease using
urine sample was assumed to be the best option. Because of complexity, expensive cost and time
consumption, the other alternatives were left out.

2.7 Proposed solution

The selected design is the one with the highest weight score. The analysis of urine characteristics
is used as an indication of the presence of liver related disorders in the patient. The device works
on spectrophotometer principle. Three light emitting diodes with different color specification such
as white, red and green light are essential to start the design. Because bilirubin absorbs violet wave
length, monochromator is paced next to the white light source, to select violet wavelength.

The first sample holder (cuvette) contains urine solution with bilirubin and its reagent diazonium
salt. In the presence of bilirubin, color of urine changes to dark violet, bilirubin absorbs violet
wavelength, and the resulting amount transmitted to photodiode can be processed and measured
in voltage. The second cuvette contains urobilinogen and the reagent P-dimethyl amino
benzaldehyde, depending on amount of urobilinogen in the solution, urine color changes to pink-
red. Urobilinogen absorbs red light and the rest will be transmitted to the photodiode. The third
urine sample contains acidic urine solution with bromothymol blue, which is an indicator to detect
change in PH value, higher acidic concentration results in dark green color, manifests higher
specific gravity. In each cases, photodiodes detect wavelength of light transmitted through the
samples and Arduino process the signal in voltage range. The design will effectively avoid false
positive results and alert the patient about his/her liver condition early.

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 Yes

Figure 2.6 Flowchart of the diagnosis system

2.8 Component list and Discussion

2.8.1 Super LEDs
LEDs which are specifically designed for higher illumination purposes with much better
brightness, hence, much better penetration into the sample urine.

Figure 2.7 Super LED

2.8.2 Heat-Sync
These are materials which are used to mimic the temperature rise in components like super
LEDs, which possess much current that can heat and blow them up. They usually are made of
copper, Aluminum and some times, alloys of both.

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 Figure 2.8 Heat sync

2.8.3 Photodiode:
The photodiode is a high speed and high sensitive PIN photodiode in a standard 5mm black plastic
package. The device is spectrally matched to visible and infrared emitting diode.

Figure 2.9 Photodiode

2.6.4 Light emitting diode

Green, red and blue LEDs are used in the design that have a capability to penetrate into urine
sample. It ranges from

Figure 2.10 Light emitting diode

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2.8.4 Cuvette
Cuvettes are small sealed containers that are designed to hold samples for spectroscopic
measurement, where a beam of light is passed through the sample within the cuvette to measure
the absorbance, transmittance and others. This measurement is done with a spectrophotometer.

Figure 2.11 Cuvettes

2.9 Device implementation plan

In order to transfer the ideal plan into actual design, electronic components such as electronic
chips, LEDs, photodiodes, super LEDs, cuvettes, Heat-Sync, Arduino and LCD are very essential.
Proper setting, arrangement and connection of each component, following the design procedure is
useful to acquire accurate and effective test results. A Programming code should be included to
run on Arduino interface that helps the processor (Arduino) to interpret the incoming signal
referring to the code. There is a need for chemical reagents such as diazonium salt,
amionbenzaldehyde and bromothymol blue that brings color change in the presence of bilirubin,
urobiliogen and high specific gravity respectively. Though it was the most challenging condition,
it has been solved by appropriately mixing colors that gives nearly similar output when urinary
products react with their specific chemical reagents.

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 CHAPTER THREE
FINAL DESIGN
4.1 Implementation Design
The implementation design involves putting the project plan into action. The device works in the
concept of spectrophotometer principle. It allows spectroscopic screening of urine sample along
with chemical reagents. Test for urinary bilirubin, urobilinogen and specific gravity together
determines either the presence of hepato-biliary obstruction or hemolysis process.

Three sample holder cuvettes are arranged in between LEDs and photodiode. LEDS that are used
in detection of bilirubin and urobilinogen are super LEDs, and the other normal LED is used in
detecting presence of specific gravity and each cuvette contains urinary bilirubin, urobilinogen and
acidic urine along with reagents. Reaction of the chemical reagent diazonium salt with bilirubin,
changes the color of bilirubin from yellow to violet. When Violet light, which is selected by
monochromator from blue light source, transmitted into urinary bilirubin, an increased amount of
bilirubin transmits a small proportion violet wavelength to the photodiode.

Test for urinary urobilinogen is based on aldehyde reaction, p-dimethyl aminobenzaldehyde in an

acidic medium, the reaction changes color of urobilinogen to pink-red. When red light transmitted
into the sample, the solution absorbs red wavelength. A small portion of red light is detected by
the photodiode.

When acidic concentration of urine increases more H+ ions are available in the urine solution,
interaction with the chemical reagent bromothymol blue changes color of urine to dark green.
When green LED transmitted in to the sample, concentrated acidic solution absorbs green
wavelength and the rest green wavelength is detected by the photodiode. This manifests the
presence of specific gravity. The result, show up, hepatic disorder.

For each case, photodiode detects amount of light transmitted from the urinary sample. Signal of
each solution is processed by Arduino mega. If presence of bilirubin and urobilinogen and more
H+ ion in urine solution increase, a Low voltage output is expected Then, LCD displays the final
result as hemolytic, hepatic or biliary obstruction and for high voltage output, LCD displays
negative result for liver diseases.

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 Figure 3.1 Implementation design flow chart

3.2 Design changes

3.2.1 Measurement change
It was planned to measure specific gravity of urine using weight sensor that is electromechanical
method. However, the measurement is changed to electrochemical system, which implements
acidity test.

3.2.2 Parameter added

Previously, it was assumed to measure amount of bilirubin and specific gravity in urine. However,
after consultation with health facility organizations and referring to researches and literatures,
testing the presence of urobilinogen in urine is added into the design.

The use of super LEDs is another addition of the initial design consideration and it was done so
due the incapability of the LEDs (normal ones) to penetrate through the sample as a result of
decreased brightness due low current drop.

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3.2.3 Parameters removed
The first design plan incorporates analyzing the change in color and smell or urine, where these
parameter is not contained in the final design.

3.3 Construction of prototype

3.3.1 Initial prototype
Electronic components such as 16 *2 LCD, Photodiode and one green LED and Arduino Mega
microcontroller are contained in initial prototype. The photodiode was placed on the breed board
open space where it was subjected to ambient light interference and much more “dark current”
around 0.57V.

Figure 3.2 Initial prototype

3.3.2 Second prototype

To improve the initial prototype measures was taken; the photodiode was placed inside a can which
was painted black to absorb all possible light rays which can alter readings. The paint was also
useful to minimize “dark current” noise to 0.1V. Components used were the same as prototype
one.

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 Figure 3.3 Prototype mock-up

3.3.3 Third prototype

Three photodiodes where used beside three LEDS, green, red and violate, which are placed in dark
can; each for bilirubin, urobilinogen and specific gravity measurements. The final prototype uses
16*4 LCD to display much more information.

Figure3.4 Third prototype using can

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3.3.4 Fourth prototype
During test, the LEDs used for samples of urobilinogen and bilirubin were unable to penetrate
through the samples that made it difficult to acquire signal at the other end which is the
photodiodes. So, the use of a light source which possess high brightness characteristics and hence,
ability to penetrate the samples was necessary. Therefore Super LEDs were used in the fourth
prototype instead of normal LEDs.

Figure 3.5 Fourth prototype to display conditions of liver diseases

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3.4 Final component lists
 Arduino Mega 2560
 Potentiometer
 LCD 16*4
 Photodiodes
 Super LEDs
 Resistor (*3) and,
 LEDs (Green, Red)
 Buzzer
 Heat-Sync

3.5 Outcome of the project

The device is capable of performing two functions: The first one is to test for the presence of
bilirubin and urobilinogen and measure specific gravity in urine. The other is to classify hepato-
biliary disorders as hemolytic, hepatic and biliary obstructions. Therefore, it is a best solution to
manifest liver diseases before getting complicated.

The device, which is used for early detection of hepato_biliary disorder, can be used:

 In any hospitals and other healthcare facilities that could provide liver functionality test, In
Ethiopia and Africa, where liver disease prevalence is high.
 Allows any individuals who are capable of affording the device, to monitor their liver
condition. Because the device is simple and easy to be used at home.
 It can effectively prevents complications as a result of late diagnosis.
 Allows diagnosis of hemolytic, hepatic and biliary obstruction of liver diseases non-
invasively.
 Minimizes workload for governmental or private hospitals
 Reduces the occurrence and prevalence of the disease in Ethiopia.

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 CHAPTER FOUR
TEST AND RESULT
4.1 Design Criteria
A test plan is used to verify and ensure that a product or system meets its design specifications and
other requirements. It helps to be sure that the device is working properly, testing of the system
based up on the criteria specified by the developers of the project is mandatory. The following
were the design criteria of the proposed solution.

4.1.1 Accuracy
Accuracy is the degree of exactness possessed by the device. Specifically for this design it can be
put as the ability to detect hepato-biliary disorders without generating false positive results. The
criteria is that it had to be at least 95% right.

4.1.2 Durability
Durability is all about the amount time in which the design performs well. Determination of
equipment life time may vary between equipment due to the different type of components that are
used. If the life of the component is known we can estimate the devices‟ lifetime or this can be
achieved through experience or assessment of the device in use, simply using the device for
evaluation. The estimated life time for the totally integrated device for this project is 3 and half
years.

The device should also be firm and compact.

4.1.3 Easy to Use

Ease of use is one of the criteria that the device is expected to have since the main end users are
target individuals which will use it in their homes. Therefore the device should require minimal
training to be operated and preliminary maintenance skills to correct it during failure.

4.1.4 Portability
Since the system is home use device, it should be comfortable to move from place to place so it
must be less that 4 Kg.

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4.1.5 Cost
Since the main aim of the project is to eradicate the drawbacks poor habit of regular check-up in
our low income society, the device should not cost more than 3000 ETB.

4.2 Testing
In order to bear out that a product or system meets its design specifications and other requirements
different methods of testing are followed depending on what is tested. And a test plan is usually
prepared by significant input from group and advisors.

4.2.1 Test for Accuracy

In order to check the accuracy of the device, real-time diagnosis was necessary. The challenge
with that was the lack of chemicals like bilirubin, urobilinogen and their re-agents. To overcome
that problem, another testing mechanism was used which is stated as following.

Three different Inks were prepared that are Violet-Blue,Dark-Green and Pink-Red. They were
prepared as they were the end results following the reaction of bilirubin with diazonium salt,
Hydronium ions (H+) with bromothymol blue and urobilinogen with P-dimethyl-amino-
benzaldehyde, respectively. This was made possible by using a working spectrophotometry
machine that can distinguish different wavelengths of different solutions with the help of
professionals at JUSH clinical chemistry Laboratory.

Four batches of solutions for each parameter were prepared according to their wavelength using
the spectroscopy machine. The batches were prepared for maximum reaction wavelength (Lambda
max) and minimum reaction wavelength (Lambda min) and two ranges were selected for
quantification purpose.

The solutions with the maximum reaction wavelength were considered as concentrated positive
samples and the solutions with the minimum reaction wavelength were taken as negative samples;
the two other solutions were arranged in decreasing order of concentration so that they can be used
as a test varying mechanism for different patient conditions.

And the results were fascinating as the device was proved to distinguish between different
concentrations of samples and classify in accordance with the theoretical assumptions. There were
no observed false positive results generated during the test so it can be said that the device is proved
to be more than 95% accurate.

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4.3 Test conducted
The following table shows that how criteria are tested and evaluated.
Table 4.1 Test conducted and evaluated

№ Feature Input Method Criteria Result

1 Cost Market Summing up <3000
production cost
2 Durability Interview and Analysis >3 years >3 and half
Quantify total years
life time of
components
3 Accuracy Real-time test Testing the device >95% 100%
results by testing
samples with
spectrophotometer
4 Easy to use an end user Observation Operation Easy to use
literates & with minimal
illiterates training
5 Portability Total weight Measuring weight <4 kg 2 Kg

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Test on progress

Figure 4.1 while performing test

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Different test results and classifications of liver disorder

Figure 5 .1 Different conditions of hepato-biliary disorder

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 CHAPTER FIVE
SUMMARY AND RECOMMENDATION

Hepato-biliary disease is a major challenge extended across the world including Africa. In regions
where it is endemic, effective treatment and eradication of the disease are often challenged by lack
of access to rapid, accurate, and affordable diagnosis and prevention system. Unfortunately, the
best diagnostic technique technique currently available requires laboratory tests and skilled
technicians. Even if there are ways to detect and measure the presence of after occurrence. Since
the best diagnostic way is to detect the presence of liver disease early to avoid complications
associated with late diagnosis. Therefore, the device plays a significant role in reducing the spread
of liver diseases and provides better diagnosis system.

The device diagnosis liver diseases using non-invasive urinalysis method and tell user whether
they are positive or negative to hemolytic, hepatic and biliary disorders’ laboratory experiment
was conducted using a spectrophotometer to check accurate interpretations of the device with
similar concentration of urine sample. The device, show up, 95% accurate test results. Currently,
this prototype is designed to express the operation of the system.

For future, the team aims:

 To apply single source of light and single detector using varying chromator.
 Introduce reagent mixing automation system

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 REFERENCE
[1] “Digestive disorder” (2019). Internet: http://www.webmed.com/digestive_disorder

[2] Steven K., MD, Professor of Medicine, Division of Gastroenterology and Hepatology. (May,
2018). “Liver Failure “. Internet: https://MSD.org/Liver Failure/Liver and Gallbladder
Disorders/Manual Consumer Version.html

[3] Hepatol J. (2019). Burden of liver disease in the world. Us National library of medicine:
National institute of health.70 (1):157-171

[4] “Ethiopian liver disease” (2017). Internet: https://www.worldlifeexpectancy.com/Ethiopian

liver disease.html.

[5] Harold E. “Liver anatomy”. Internet: https://www.up.bgmu.u/images/home/liveranatomy

[6]“Liver_anatomy_and_function”.Internet:https://www.medicinenet.com/liver_anatomy_and_fu
nction/article.html

[7] “Liver physiology and anatomy” (2018).internet: https://www.web.uniz.it/uploads/liver

phyiology and anatomy.

[8] Steven K. Herrine, MD, Professor of Medicine, Division of Gastroenterology and

Hepatology. Sidney Kimmel Medical College: Thomas Jefferson University

[9] Mcmurry,et al. Fundamentals of general organic and biological chemistry; Body fluids, the
kidney and urine formation. “Introductory
internet:https://www.chem.libertexts.org/Bookshelves/Introductory_chemistry

[10] Simerville J., Maxted W., Pahira J., (March 2005). "Urinalysis: a comprehensive review".
American Family Physician.71 (6): 1153–62. PMID 15791892

[11] “Bilirubin in urine”. internet:https://www.nlm.nih.gov/?_ga=12348767.1671481098

[12] Kevin F., Joseph W., (2014).Laboratory medicine. Clinical significance of urine. (45):59__61

[13] “Urobilinogen in urine”. internet:https://www.labce.com spg506379_urobilinogen –

reaction.aspx

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[14] Denise K. (March, 2015).Understanding urinalysis. National kidney foundation. The
university of Texas: south western medical center.

[15] Denise K., (March 2015).Understanding urinalysis. National kidney foundation. The
university of texes; south western medical center.

[16] “Liver function test’. Internet: http://www.stanfordhealthcare.org/medical-conditions/liver-

kidneys-and-urinary-system/chronic-liver-disease/diagnosis/liver-function-tests.html

[17] “Liver anatomy _and _function”. internet:https://www.medicinent.com/liver

antomy_and_function/article.html

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 APPENDICES
Appendix A
End user worksheet

Name of End user: ________________________________

Signature: _______________

Title of End user: _________________________________

Date: ___________________

Question 1: What features do you like best about the design? Why?

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

Question 2: What features need improvement, replacement, removal, or modification? Why?

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

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Question 3: What additional features would you like to see for this design? Why?

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

Photograph:

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Appendix B
A. Arduino Mega

Single board microcontroller kits for building digital device and interactive objects that can sense
and control objects in physical and digital world. Arduino Mega is used for programming based
on level of voltage and gives instruction for the LCD display healthy or cancer detected. The mega
2560 R3 Board is 100% compatible with Arduino. Powered via the USB connection or with an
external power supply. The power source is selected automatically. The ATmega2560-16au has
256 KB of flash memory for storing code (of which 8 KB is used for the bootloader), 8 KB of
SRAM and 4 KB of EEPROM (which can be read and written with the EEPROM library).

Figure 6.1 Arduino mega

B. LCD

LCD stands for Liquid Crystal Display .is a flat panel display or other electronically modulated
optical device that uses the light modulating properties of liquid crystal .liquid crystals do not
emit light directly, instead using a back light or reflector to produce images in color or
monochrome. It is 16x4 LCD that used for displaying the output voltage in terms of word.

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 Figure 6.2 LCD

C. Other components used

Potentiometer, Resistor, breed board and Connecting tables

Figure 6.3 Other components used

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Appendix D
A. Basic principles of spectrophotometry and their application in chemical analysis
Spectrophotometry is based on the measurement of light absorbed or
transmitted by a chromogen placed between the light source and light intensity
measuring device. The wavelength where the chromogen exhibits maximum
absorbance (Xmax) under the experimental conditions and the extinction coefficient (e)
of the chromogen are the two spectrophotometric characteristics of great importance
in chemical analysis. These are experimentally evaluated by recording the absorbance
of the chromogen under given experimental conditions at different wavelengths of
light. The quantitative spectrophotometry is based on the two principal laws of
photometry namely Lambert’s law and Beer’s law. These can be briefly stated as
follows.

B. Beer’s Lambert Law

In a homogenous medium, light intensity lose due to the absorption as it passes through an
absorbent medium transmittance of the light is given by:

I out / I in=e-µa*d…………………………………. (1.1)

Where: Iin is intensity of incident light, I out is intensity of transmitted light at distance d (mm)
from input, µa is attenuation coefficient of a medium. Transmission can be described as:
I out/Iin=T………………………………….. (1.2)

Then absorption can be obtained by:

A= -log T…………………………………….. (1.3)

C. V-I characteristics of photodiode

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 Figure 6.4 VI characteristics of photodiode

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Appendix E

Preparation of test samples

A. Bilirubin reaction with Diazonium salt

The maximum wavelength for the solution is 455 nm which lays in the blue light spectrum
specifically the violet region. This wavelength indicates maximum concentration of bilirubin.
Similarly, the minimal reaction wavelength is 492 nm.

For the procedure a violet ink was used; which was mixed with dilute saline solution (resembling
some characteristics of urine) and the proper wavelength was set by trial and error using
spectrophotometer machine by the assistance of lab technician.

Hence 4 batches were prepared in the following proportion using a highly precise micro-pipette

Batch-1
4ml of saline solution + 1ml of Ink
Transmittance 0.02%
Wavelength of 454 nm
Max concentration
Batch-2
4.9ml of saline solution + 0.1ml of Ink
Transmittance 0.04%
Batch-3
4.75ml of saline solution + 0.25ml of Ink
Transmittance 0.56%
Batch-4
4.95ml of saline solution + 0.05ml of Ink
Transmittance 99.1%
Wavelength of 490 nm
Min concentration

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 B. Urobilinogen reaction with P-dimethyl-amino-benzaldehyde
The maximum wavelength for the solution is 635 nm which lays in the red light spectrum
specifically the pink region. This wavelength indicates maximum concentration of bilirubin.
Similarly, the minimal reaction wavelength is 615 nm.

For the procedure a pinkish red ink was used; which was mixed with dilute saline solution
(resembling some characteristics of urine) and the proper wavelength was set by trial and error
using spectrophotometer machine by the assistance of lab technician.

Hence 4 batches were prepared in the following proportion using a highly precise micro-pipette

Batch-1

4.5ml of saline solution + 0.5ml of Ink

Transmittance 0.02%
Wavelength of 634 nm
Max concentration
Batch-2
4.75ml of saline solution + 0.25ml of Ink
Transmittance 12.2%
Batch-3
4.9ml of saline solution + 0.1ml of Ink
Transmittance 58.4%
Batch-4
4.95ml of saline solution + 0.05ml of Ink
Transmittance 98.2%
Wavelength of 612 nm
Min concentration
C. Reaction of urine with bromothymol blue due to release of H+ ions
The maximum wavelength for the solution is 500 nm which lays in the green light spectrum
specifically the dark green region. This wavelength indicates maximum concentration of bilirubin.
Similarly, the minimal reaction wavelength is 580 nm.

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For the procedure a Dark Green ink was used; which was mixed with dilute saline solution
(resembling some characteristics of urine) and the proper wavelength was set by trial and error
using spectrophotometer machine by the assistance of lab technician.

Hence 4 batches were prepared in the following proportion using a highly precise micro-pipette

Batch-1

4.3ml of saline solution + 0.7ml of Ink

Transmittance 0.01%
Wavelength of 502 nm
Max concentration
Batch-2
4.5ml of saline solution + 0.5ml of Ink
Transmittance 1.66%
Batch-3
4.9ml of saline solution + 0.1ml of Ink
Transmittance 28.4%
Batch-4
4.98ml of saline solution + 0.02ml of Ink
Transmittance 98.2%
Wavelength of 576 nm
Min concentration. These batches were the solutions used as samples to test the device.

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Appendix F

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APPENDIX G
ACRONYMS
WHO: world health organization
LED: Light emitting diode
LCD: liquid crystal display

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