Requirements For The Urine Analyzer Biology Essay

Table of contents

Introduction

This project is collaboration between the Universitair Medisch Centrum Groningen(Hospital in Groningen; UMCG) and the Center of Excellence for Sensor Innovations (Hanze Institute of Technology, Assen; CENSI)

Abnormal (sudden or large) changes in the ion levels in urine might indicate a failure of organ. At this time, measurements of the quantities of ions in urine take at least 24 hours. Whenever this time can be reduced, doctors can receive an early warning and hereby react quicker to critical changes in the health of patients.

There have been other project groups working on this project to find the best way to analyze ion levels in urine. They concluded ion-selective electrode technology is the best possible measurement technology. The other project groups already got a Blood Gas Analyzer with ion-specific electrodes from the UMCG. For us the challenge to rebuild this Blood Gas Analyzer to an Urine Analyzer. In this project we will measure the range of all the ion-selective electrodes in the machine. The range of the ions in urine is wider than in blood, so we have to check the accuracy of the ion-specific electrodes for measurements outside the range of the ions in blood. We also have been asked to make a tube system from the catheter to the Urine Analyzer, which includes a volume measurement.

During the 20 weeks of this minor we managed to enhance the machine to measure the ion-levels of urine, outside the range of blood. We also made a working tube system, with automated valves. We took the interesting parts of the Blood Gas Analyzer, and made our own machine on a wooden board. This was the most invasive way to make the electronic part of the machine work automatically.

There is still a lot of work to do for the next project group, to let the machine work properly. Eventually the project group need to do some tests with the machine on real patients.

Overall Requirements

The previous group came up with some requirements for the urine analyzer. Those requirements are changed a bit and we added some requirements. In this chapter we will mention all the requirements needed to complete the project.

The urine analyzer has to be able to:

- Measure the most significant ions in urine (in terms of the indication of failure in organs).

The following data has to be gathered:

- The relative amount of the following ions(data needs to be available per item):

- Sodium

- Potassium

- Calcium or chloride (depends which ion is more important to measure, the machine

can only do one of these at this moment)

- The pH value of the solution

- Measure the total amount of urine during the day

In the current situation, the nurse will take a look at the waste bag with urine which indicates the total amount of urine. We made a buffer in the system which counts the amount of times the buffer empties. This way you will get a more accurate measurement.

- Analyze urine within 15 minutes

Currently, doctors and patients have to wait for 24+ hours in order to get results from urine tests. However, changes in the composition of urine can indicate internal organ failure. By reducing the time to 15 minutes to analyze urine, medical staff can react quicker and can possibly save lives of critically ill people.

- Be able to autonomously analyze urine of patients with a catheter every 15 minutes

In the current situation, a nurse has to take samples of certain patients every hour in order to analyze the urine. The device that we have developed during this project is able to sample and analyze urine automatically every 15 minutes or when there is enough urine stored to analyze. This reduces the operating costs of regular urine analysis.

- Be small enough so that the machine can be placed near to a patients bed

The device we made is not small yet, because it is a prototype. Future project groups first have to test this device before it can be made smaller, by for example Siemens. They are really interested in the outcome of our results and might want to invest in this machine when it works properly.

Background Information Urine

The urinary system consists of the kidneys, ureters, urinary bladder, and urethra. Changes in the urine value can be caused by every part of the urinary system.

The urinary system produces urine by a process of filtration, reabsorption and tubular secretion. This way water, sugars, minerals and other compounds won’t be wasted.

Urine contains, next to water, an assortment of inorganic salts and organic compounds, including proteins, hormones, and a wide range of metabolites, varying by what is introduced into the body.

Because of some pathologies you can also find compounds in the urine, you normally wouldn’t find in there. You will for example find sugar in the urine when the patient suffers from diabetes.

Apart from finding pathologies through examine the urine chemical analysis, you can also examine the urine by looking at it. The color can give you a good impression of the pathology in the urinary system:

- Dark yellow urine is often indicative of dehydration.

- Yellowing/light orange may be caused by removal of excess B vitamins from the bloodstream.

- Certain medications such as rifampin and phenazopyridine can cause orange urine.

- Bloody urine is termed hematuria, a symptom of a wide variety of medical conditions

- Dark orange to brown urine can be a symptom of jaundice, rhabdomyolysis, or Gilbert's syndrome.

- Black or dark-colored urine is referred to as melanuria and may be caused by a melanoma.

- Pinkish urine can result from the consumption of beets.

- Greenish urine can result from the consumption of asparagus.

- Reddish or brown urine may be caused by porphyria (not to be confused with the harmless, temporary pink or reddish tint caused by beeturia).

Normal values urine (mmol/L)

Sodium  40-250 mmol/24h; The sodium value is important to detect renal failure. You can see it when the level of potassium decreases. For a one time urine sample the value will be 20>mmol

Potassium  25-125 mmol/24h; In case of GI (Gastro-Intestinal) loss of potassium, the urine potassium will be low. In case of renal loss of potassium, the urine potassium levels will be high.Decreased levels of urine potassium are also seen in hypoaldosteronism and adrenal insufficiency.

Calcium Female 20-275mmol/24h and male 25-300 mmol/ 24h; An abnormally high level is called hypercalciuria and an abnormally low rate is called hypocalciuria.

pH 4.5-8 (5.5-6.5)

Kidney function

The kidney or ren in medical terms is an organ that regulates the water in the body, removes toxins and drugs, releasing hormones into the blood, regulates blood plasma, regulates the acid-base (alkaline) ratio of the blood and regulates blood pressure. The most important function of the kidney is removing toxins, drugs and water from the blood. Waste compounds of for example the muscles are transported by the bloodstream. Those compounds are toxic for the human body and will be removed by the kidneys. The kidneys regulate the amount of moisture in the body. After drinking a lot of water the kidneys produce extra urine, but if you sweat a lot the kidneys produce less.

The produced urine is transported by the ureter to the bladder. In this urinary tract a lot of pathologies can occur. I will explain the most common.

- Acute tubular necrosis (ATN);

Occurs when the tubules are damaged. Therefore, they are incapable of actively reabsorbing sodium. You will get lower levels of sodium in the urine: > 40 mmol/L.

-Kidney stone;

Most common is the calcium containing stone (80%), but the patient can also suffer from a uric acid stone (5-10%). The pH value of the urine will increase if the patient suffers from a kidney stone.

- Glomerulonephritis;

Renal disease which is mostly found in both kidneys. If the patient suffers from glomerulonephritis, you will find blood or protein in the urine. But in the worst case scenario the patient will suffer from a renal failure. If this happens the kidneys won’t work anymore.

- Hydronephrosis;

The enlargement of one or both of the kidneys caused by obstruction (kidney stone) of the flow of urine. You will first notice hydronephrosis by measuring the urine. The volume will decrease. If hydronephrosis won’t be detected in an early stadium, the patient will develop urinary tract infections. This can lead to the development of additional stones and blood or pus in the urine. If complete obstruction occurs, the patient will eventually suffer from kidney failure.

- Kidney tumors; Wilms’ tumor&Renal cell carcinoma

The most common kidney cancer in adults is Renal cell carcinoma. You will notice an abnormal dark, rusty or brown urine color because of blood in the urine. You can also notice a lower calcium level in the urine.

Wilms’ tumor or nephroblastoma is mostly found in children and rarely found in adults. You will find blood in the urine if the patient suffers from Wilms’ tumor.

- Nephrotic syndrome;

Because of damage to the glomerulus there will enter a large amount of protein of the blood into the urine.

- Pyelonephritis;

Infection of the kidneys which is frequently caused by complication of a urinary tract infection. You will find nitrite and white blood cells in urine.

- Renal failure;

The kidney fails to filter toxins and waste products from the blood. This way the acid level in the urine will increase, which causes a decrease in the pH value. You will get abnormal levels of potassium, calcium and phosphate in the urine and you will also get blood and protein loss in the urine.

- Polycystic kidney disease;

Characterized by the presence of multiple cysts in both kidneys. This will affect the intracellular transport of calcium, which will lead to a decrease of calcium in the urine.

- Cystinosis;

Occurs when the function of cells in renal tubules are impaired, leading to abnormal amounts of carbohydrates and amino acids in the urine, excessive urination, and low blood levels of potassium and phosphates.Cystinosis is a rare genetic disorder that causes an accumulation of the amino acid cystine within cells, forming crystals that can build up and damage the cells. These crystals negatively affect many systems in the body, especially the kidneys and eyes. Definitive diagnosis and treatment monitoring are most often performed through measurement of white blood cell cystine level using tandem mass spectrometry.

- Diabetes insipidus;

A condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine.Urinalysis demonstrates a dilute urine with a low specific gravity. Urine osmolarity and electrolyte levels are typically low.Adults with untreated DI may remain healthy for decades as long as enough water is consumed to offset the urinary losses. However, there is a continuous risk of dehydration and loss of potassium.

- Nephritis;

It is a disturbance of the glomerular structure with inflammatory cell proliferation. This can lead to reduced glomerular blood flow, leading to reduced urine output (oliguria) and retention of waste products (uremia). As a result, red blood cells may leak out of damaged glomeruli, causing blood to appear in the urine (hematuria). Low renal blood flow activates the renin-angiotensin-aldosterone system (RAAS), causing fluid retention and mild hypertension.

- Alport syndrome;

Because of mutations the basement membranes of the kidneys are not able to filter waste products from the blood and create urine normally, allowing blood and protein into the urine.

- Vesicoureteral reflux;

The urine will have a reflux of the urine from the bladder back in to the ureter. This can cause an urinary tract infection. If this happens, you will find white blood cells in the urine. But a reflux is mostly find earlier, because of the flank pain the patient suffers from.

- Goodpasture's syndrome;

A rare autoimmune disease in which antibodies attack the lungs and kidneys, leading to bleeding from the lungs and to kidney failure. You will find a small amount of blood and protein in the urine. You can also notice a decreased volume output of urine.

Because of the rapid advance of the disease the kidney function can be completely lost in a few days.

Changes in sodium, potassium, calcium and pH level in urine

The levels of sodium, potassium, calcium and urine fluctuate a lot in urine. I will explain the reasons why those levels may be increased or decreased.

Sodium level increased occurs in:

- Too much salt in the diet

- Certain medications, such as diuretics

- Adrenal gland insufficiency; less aldosterone production (a mineralocorticoid) which regulates sodium, potassium and water retention. Because of this the urinary lose a lot of sodium.

- Salt-wasting nephropathy; a rare endocrine condition featuring hyponatremia (low blood sodium concentration) and dehydration in response to trauma/injury or the presence of tumors in or surrounding the brain. This results in an excretion of sodium.

Sodium level decreased occurs in:

- Aldosteronism; is characterized by the overproduction of the mineralocorticoid hormone aldosterone by the adrenal glands. Aldosterone causes increase in sodium and water retention and potassium excretion in the kidneys.

- Cirrhosis; is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative leading to loss of liver function. This results in an excretion of water which results in an decreased sodium level in urine.

- Diarrhea and fluid loss; because of diarrhea and fluid loss you will lose a lot of water with minerals, what results in a decreased level of sodium in the urine.

- Hepatorenal syndrome; a life-threatening medical condition that consists of rapid deterioration in kidney function or full liver failure. It results in a low urine volume (less than 500 mL/per day), low sodium concentration in the urine, a urine osmolality that is greater than that in the blood, the absence of red blood cells in the urine, and a serum sodium concentration of less than 130 mmol/L.

- Kidney failure; a medical condition in which the kidneys fail to adequately filter waste products from the blood. This will result in an increased acid level, raised level of potassium and decreased levels of calcium and sodium.

- Nephrotic syndrome; a nonspecific disorder in which the kidneys are damaged. Because of this the kidneys will leak large amounts of protein. The patient will gain a lot of edema with retention of sodium and water, which results in a low level of sodium in urine.

Potassium level increased occurs in:

- Primary or secondary aldosteronism; is characterized by the overproduction of aldosterone by the adrenal glands. This causes an increase in sodium and water retention and potassium excretion in the kidneys.

- Excess Potassium intake

Potassium level decreased occurs in:

- Acute renal failure; the kidney fails to filter toxins and waste products from the blood. This way the acid level in the urine will increase, which causes a decrease in the pH value. You will get abnormal levels of potassium, calcium and phosphate in the urine and you will also get blood and protein loss in the urine.

- Potassium-Sparing diuretics

- Diarrhea; because of diarrhea you will lose a lot of water with minerals, what results in a decreased level of potassium in urine.

- Hypokalemia; the condition in which the concentration of potassium in the blood is low.

Calcium level increased occurs in:

- Hypercalciuria; the condition of elevated calcium in the urine.

- Hyperparathyroidism; overactivity of the parathyroid glands. This results in excess production of parathyroid hormone (PTH). The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels. Excessive PTH secretion may lead to hypercalcaemia (raised calcium level).

- Cancer

Calcium level decreased occurs in:

- Hypoparathyroidism; is decreased function of the parathyroid glands with underproduction of parathyroid hormone. This can lead to a low levels of calcium.

- Not getting enough vitamin D

- Kidney problems; a medical condition in which the kidneys have problems to filter waste products from the blood. This will result in an decreased level of calcium.

- Malnutrition caused by diseases like celiac disease, pancreatitis and alcoholism.

pH level decreased (acidic) occurs in:

- Acidosis; an increased acidity in the urine.

- Respiratory diseases in which carbon dioxide retention occurs and acidosis develops

- Renal tubular acidosis; a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine.

- Urinary tract obstruction; can be caused by a kidney stone. The urine will accumulate and this results in an increased pH level in urine.

- Chronic renal failure; is a medical condition in which the kidneys fail to adequately filter waste products from the blood. This results in an increased acidic level.

pH level increased(alkaline) occurs in:

- Respiratory diseases that involve hyperventilation (blowing off carbon dioxide and the development of alkalosis)

- Diarrhea; because of diarrhea you will lose a lot of water with minerals, because of this the pH level will increase and will becomealkaline.

- Starvation and dehydration; your body doesn’t have enough water in the body and because of this the pH level will raise and will become alkaline.

Current Situation

The other project groups already explained that analyzing the urine nowadays takes at least 24 hours. With this project we try to make a device that is able to measure the urine automatically every 15 minutes. To make this device we use the Blood Gas Analyzer donated by Siemens. The ions we want to analyze in urine are the same as the ions which are analyzed by the Blood Gas Analyzer.

This 20 weeks we looked at the range of the ion-specific electrodes in the Blood Gas Analyzer. The range of those ions in urine is much wider than in blood. Luckily the ion-specific electrodes have a greater range than expected, so it is possible to analyze urine with those electrodes.

To make the device automatically we had 2 options to choose from. We could build a device around the Blood Gas Analyzer which would abolish the system of the Blood Gas Analyzer or we could make our own system and take out the parts of the Blood Gas Analyzer we need. We decided to take apart the Blood Gas Analyzer and make our own device. For this prototype we used a wooden plate to attach all the parts we needed to make the Urine Analyzer.

We also made a tubing system with automated valves. This tubing system will lead the urine from the catheter to the Urine Analyzer and the waste bag. We also included a buffer, so we can count the quantity of urine and this way we are sure of having enough urine for a measurement.

Changes Blood Gas Analyzer

The machine Siemens provides us is a RAPIDLab 348. This device is designed to analyse blood and is used in hospitals and other institutions were blood analysing is necessary. The device is able to measure the pH, the blood gases pCO2, pO2, the electrolytes Na+, K+, Ca++, and the Hematocrit HCT. For the urine project the sensors we need are the electrolytes, these are important for the wellbeing of a patient.

The sensor unit of the RapidLab 348 was taken and placed on a wooden plate. All the other components needed were placed around the module on the front and back of the plate.

Sensors and Solutions

The 348 Blood Gas Analyzer utilizes potentiometric sensors to measure the ion concentrations in the sample. During analysis, a potential is observed at the sensors due to the interaction between the sample and the electrolyte solution inside the glass membrane of each sensor. This potential is related to the amount of the specific ion in the sample and can be expressed by the Nernst equation [1]:

where and are the concentrations of Ox and Red, respectively, n is the number of electrons transferred, F is the Faraday constant, R is the gas constant, T is the absolute temperature, and is the electrode potential at a standard state.

Considering measurements made at room temperature (around) and adopting the following values for the physical constants [2]

then,

As this device has been built to measure blood, it is necessary to verify the feasibility of using the same sensor to measure concentration in urine, since the range of values can be completely different, as showed in Table .

Table - Range comparison

Measurement range (mmol/L) [1]

Range in urine (mmol/L)

Sodium (Na+)

80 – 200

25 – 250 [2]

Potassium (K+)

0.50 – 9.99

25 – 120 [3]

Calcium (Ca++)

0.20 – 5.00

2.5 – 7.5 [4]

Chloride (Cl-)

40 – 160

0 – 300 [5]

pH

6.001 – 8.000

4.5 – 8.5 [6]

In order to verify the ability of these sensors to measure ion concentrations in wider ranges, which is commonly observed in urine, it is necessary to know the relation between the output voltage and the respective concentration. The output voltage for each sensor was measured for some solutions prepared in the chemistry laboratory, and consequently with known concentrations. These solutions had concentrations within the blood range, therefore the accuracy in the measurements is guaranteed by the manufacturer. With these set of data, it is possible to determine the mathematical relation which allows to convert a voltage into a concentration. The next step is to validate this relation for concentrations outside the initial range, also measuring the output voltage and comparing the actual concentration with that one predicted by the equation found previously. Each sensor was tested using solutions with concentrations even in a wider range than the commonly observed in urine to assure all values of interest could be measured accurately.

Sodium sensor

Initially, a solution of sodium chloride (NaCl) 250 mmol/L was prepared and diluted to obtain new solutions with concentrations in intervals of 25 mmol/L, until reach the concentration of 25 mmol/L. Further measurements were performed using a solution of 500 mmol/L and decreasing by 50 mmol/L until 300 mmol/L; these high values were tested to assure this sensor will provide good results even in extreme cases. For each concentration, the measurements were repeated 5 times, as shown in Table .

Table - Sodium measurements

Concentration (mmol/L)

Output voltage (mV)

Average (mV)

25

35.39

43.54

45.76

46.42

44.12

43.05

50

57.22

57.19

59.73

57.83

56.98

57.79

75

65.75

66.64

66.99

68.27

66.96

66.92

100

73.45

73.29

73.69

73.63

74.23

73.66

125

77.64

78.55

78.19

78.05

77.85

78.06

150

82.06

82.14

82.86

82.81

82.86

82.55

175

88.04

87.56

87.62

87.03

87.52

87.55

200

90.91

90.44

89.24

90.81

90.40

90.36

225

93.12

90.77

92.24

93.63

93.70

92.69

250

94.76

95.27

96.16

95.71

96.18

95.62

300

98.78

98.91

99.50

99.46

100.60

99.45

350

103.21

103.49

103.41

103.81

104.31

103.65

400

107.65

107.73

107.41

107.62

107.68

107.62

450

110.77

110.96

111.17

111.37

110.79

111.01

500

114.41

114.47

113.95

114.17

114.27

114.25

To find the mathematical relation, only the values for concentration between 100 and 200 mmol/L were used (as said before, to guarantee the accuracy provided by the manufacturer). A linear regression using the output voltage and the natural logarithm of the concentration provides the desired equation:

This equation shows the angular coefficient is close to 25.35, which is the value theoretically predicted for these conditions. Using this equation to test the accuracy for concentrations outside the initial range, it can be observed that the percentage error is acceptable for this application, as show in Table .

Table - Concentration error for sodium

Concentration (mmol/L)

Expected values (mmol/L)

Error (%) (concentration)

25

29.69

18.75

50

53.85

7.70

75

77.86

3.82

100

102.21

2.21

125

122.07

2.34

150

146.34

2.44

175

179.14

2.37

200

200.64

0.32

225

220.45

2.02

250

248.09

0.77

300

289.63

3.46

350

343.12

1.97

400

402.82

0.70

450

461.99

2.67

500

526.62

5.32

Figure shows each measured value and the predicted transfer function for the sodium sensor.

It can be observed that there are small deviations between the measured and predicted values. However, for concentrations smaller than 25 mmol/L, the output voltage varies a lot, even for small changes in concentration. This can be observed in a linear scale graph (Figure ), which shows that the transfer function approaches to a vertical line.

Figure - Sodium sensor (single-logarithm scale)

Figure - Sodium sensor (linear scale)

Potassium sensor

Following the same procedure described above, a solution of potassium chloride (100 mmol/L) was prepared and posteriorly diluted. In order to facilitate the dilution, another solution of KCl was prepared (10 mmol/L) to measure the low concentrations. The measured values for each concentration are shown in Table .

Table - Potassium measurements

Concentration (mmol/L)

Output voltage (mV)

Average (mV)

0.5

44.62

38.90

40.94

36.83

40.67

44.43

41.07

1

52.32

51.38

50.97

51.29

51.48

51.57

51.50

2

66.59

66.67

67.15

66.80

65.62

66.13

66.49

3

75.33

75.09

75.65

75.84

75.28

74.96

75.36

4

80.26

82.99

82.18

82.34

83.17

80.29

81.87

5

86.15

85.86

85.96

86.28

86.92

86.36

86.26

6

92.23

90.58

91.44

91.36

90.73

92.13

91.41

7

94.76

93.69

93.80

95.93

95.26

94.89

94.72

8

97.42

97.26

98.68

98.72

97.42

97.45

97.83

9

100.31

100.57

101.69

100.85

100.49

101.89

100.97

10

104.42

105.01

104.88

103.49

104.55

104.33

104.45

20

122.15

122.48

124.97

124.93

124.66

124.94

124.02

30

133.15

132.98

133.66

133.69

134.45

134.24

133.70

40

139.64

139.58

140.89

140.15

141.21

140.63

140.35

50

146.45

146.71

146.27

146.37

146.65

146.62

146.51

60

150.03

150.01

150.42

150.76

151.36

151.14

150.62

70

154.72

154.22

154.63

154.79

154.74

154.68

154.63

80

157.03

156.83

158.17

158.21

157.92

158.27

157.74

90

161.08

160.80

161.22

161.23

161.03

160.91

161.05

100

163.12

163.09

163.64

163.15

162.88

163.35

163.21

These data are related according to the following equation:

Once again, the angular coefficient is close to the predicted value. shows the percentage error for the concentration outside the initial range.

Table - Concentration error for potassium

Concentration (mmol/L)

Expected values (mmol/L)

Error (%) (concentration)

0.5

0.69

37.74

1

1.06

5.80

2

1.96

1.98

3

2.82

5.89

4

3.69

7.73

5

4.42

11.59

6

5.47

8.92

7

6.26

10.54

8

7.12

11.06

9

8.10

10.03

10

9.34

6.57

20

20.91

4.53

30

31.12

3.75

40

40.93

2.32

50

52.73

5.47

60

62.45

4.08

70

73.65

5.21

80

83.69

4.62

90

95.89

6.54

100

104.80

4.80

Figure shows each measured value and the predicted transfer function for the potassium sensor.

It can be noted that the measured values are close to the predicted function, especially for higher concentrations, which corresponds to the common values observed in urine.

Figure - Potassium sensor (single-logarithm scale)

Calcium sensor

For this sensor, a solution of calcium chloride (10 mmol/L) was initially used, and posteriorly diluted in intervals of 0.5 until 0.5 mmol/L. Each measured value is shown in Table .

The transfer function obtained with these data is shown below:

This solution contains the ions Ca2+ and Cl-; since the number of transferred electrons is 2 (corresponding to n in the Nernst equation), then the expected angular coefficient for this sensor is 12.6739, which is close to the experimental value. Error: Reference source not found shows the percentage error for the concentration outside the initial range.

Table - Calcium measurements

Concentration (mmol/L)

Output voltage (mV)

Average (mV)

0.5

47.48

45.15

44.84

47.11

46.03

46.12

1.0

53.18

49.75

49.78

52.49

52.91

51.62

1.5

57.93

57.71

57.83

57.16

57.75

57.68

2.0

60.17

61.09

60.35

60.56

60.81

60.60

2.5

63.35

63.39

63.48

62.90

63.21

63.27

3.0

65.63

64.86

64.45

64.87

65.42

65.05

3.5

66.84

66.39

66.43

66.50

66.57

66.55

4.0

68.48

67.93

68.63

68.60

68.62

68.45

4.5

69.75

69.01

70.09

69.49

69.38

69.54

5.0

70.42

70.91

70.82

70.22

70.74

70.62

5.5

71.99

71.23

71.16

71.58

71.90

71.57

6.0

72.63

72.87

72.73

72.49

72.85

72.71

6.5

73.18

73.58

73.97

73.80

73.49

73.60

7.0

74.45

73.94

74.52

74.26

74.61

74.36

7.5

75.55

75.03

74.98

75.37

75.14

75.21

8.0

75.38

75.06

75.87

75.94

76.97

75.84

8.5

76.72

76.23

76.46

76.48

76.62

76.50

9.0

77.23

76.99

77.50

76.84

77.35

77.18

9.5

77.60

77.85

77.69

77.83

77.72

77.74

10.0

78.37

78.34

78.17

78.45

78.41

78.35

Table - Percentage error for calcium

Concentration (mmol/L)

Expected values (mmol/L)

Error (%) (concentration)

0.5

0.54

7.04

1.0

0.88

11.65

1.5

1.53

2.27

2.0

2.00

0.09

2.5

2.55

2.13

3.0

3.00

0.10

3.5

3.44

1.63

4.0

4.10

2.40

4.5

4.52

0.55

5.0

4.99

0.16

5.5

5.44

1.03

6.0

6.04

0.67

6.5

6.55

0.78

7.0

7.02

0.22

7.5

7.59

1.15

8.0

8.03

0.43

8.5

8.53

0.36

9.0

9.08

0.85

9.5

9.55

0.50

10.0

10.09

0.94

Figure shows each measured value and the predicted transfer function for the potassium sensor.

Figure - Calcium sensor (logarithm scale)

The analysis of the above figure also leads to the conclusion that the use of this sensor is appropriate for measurements in urine, due to the relative small errors between the actual and measured values.

pH sensor

The measurements with this sensor used 3 standard solutions with known pH, covering all the range of values observed in urine. Table contains the output voltages for these standard solutions and 2 more solutions provided together with the 348 Blood Analyzer.

Table - pH measurements

pH

Output voltage (mV)

Average (mV)

4

495.64

495.29

494.59

494.1

494.73

497.01

496.01

495.34

7

324.41

324.44

324.41

324.99

324.96

324.98

325.32

324.79

10

160.09

160.1

163.46

163.41

163.65

170.23

171.26

164.60

7.5425

292.83

292.64

292.66

291.51

291.45

290.53

290.24

291.69

7.1935

315.56

315.18

315.03

314.01

313.93

312.4

310.29

313.77

These values are related according to the following equation:

Since , this equation can be rewritten in terms of concentration, as in the general form of Nernst equation:

Note that the angular coefficient is close to the expected value. Table shows the error in concentration for each value considered.

Table – Percentage error for pH

Concentration (mmol/L)

Expected values (mmol/L)

Error (%) (concentration)

4

3.97

0.78

7

7.06

0.89

10

9.97

0.31

7.5425

7.66

1.60

7.1935

7.26

0.96

Figure shows each measured value and the predicted transfer function for the pH sensor.

Figure – pH sensor

It can be observed that all values measured are very close to the prediction of the transfer function, representing small errors.

Considerations

All sensors analyzed showed good response in the measurements of broader ions concentration, representing your ability to be used in urine applications.

The considered output voltage in these measurements is the value read in the screen of the 348 Analyzer, which represents the voltage directly in the electrodes, before the amplification. As in the current configuration the values are measured after the amplifier circuit (shown in Figure ), then each value read was multiplied by the gain, which is

.

Figure - Amplifier Circuit

Data Acquisition System

Data collection

The recorded data from the machine needs to be collected and shown in a clear understandable and visible way. The data is therefore stored in a database and recalled from a website. This website is made to be used on tablets and laptops for a quick reading of the latest values.

The data is collected via an Arduino which reads the voltages from the sensors. The voltage values are send from the Arduino over the serial line to the computer. The Java program running on the computer listens continuously to the serial line. When data is available it will collect it and send it to a database.

A web interface has been prepared to read data from the database and display this in a graph and a table. The table shows the last recorded value and the graph shows the data for the past 24 hours.

The next chapters will explain each of these steps in more detail.

Microcontroller

The system uses an Arduino Mega 2560 to perform all the tasks. This microcontroller provides everything needed to create the system, it runs at 16MHz, and has 256kb flash memory. It is capable of serial communication as well as spi, I2C. Others features include PWM and interrupts.

Program flowD:\Dropbox\Urine Sensor\Flow chart\urineflowchart.png

The software on the Arduino Mega is programmed using the Arduino environment provided by Arduino.

The flow of the program is described in the sketch on the right. The program contains several functions, every function is responsible for executing a specific part of the code. When the urine machine is powered up it initializes, setting all the parameters and cleaning the sensors before the first sample is presented. Then a 15 minute loop is started. If after this loop ended and enough urine is present a sample will be measured and stored.

If after 15 minutes there is not enough urine present the system will wait until there is enough.

After each measurement the sensor and tubing is rinsed.

Java

The computer program is set up to listen to the serial line. As soon as data becomes available it will store it temporary and it will look for certain specific lines. The lines (pH, Na+, K+ and Ca+) are followed by the recorded value from the Arduino. When all values are known and the line is empty the program will continue to send the available data to a local database.

Database and web interface

The database has been set up for quick and easy storage. The database will store the patient ID, operator ID, the time at which the measurement was taken and the values for each of the different sensors. Every measurement there will be those six entries.

As for the web interface, it has been built in such a way that it is easy and visible. The user will be able to enter the patients ID number and after submitting this see the available data. Data displayed is the patient ID, the operator ID, pH, Na, K, Ca and the time at which the last recording has been recorded by the sensors. Under each of the recorded values a button is visible which allows the user to see the data from this specific patient from the last 24 hours. This way the user is able to see what the results of the urine measurements are and what the course of the measurements have been over the last 24 hours.

This web interface makes it easy to quickly see the most important data from this specific patient.

Results

The prototype is tested with prepared samples instead of real urine, therefore there is a chance that testing the device with urine gives complications e.g. cells that are in the urine could decrease the flow though the valves of the device or interfere with the sensors.

The buffer is using LED’s and light sensitive sensors that indicate whether there is stored enough urine in the buffer to analyze or if the buffer is full. This is tested with clear water, due to the color and translucency of the urine these sensors might not give the right values, which leads to a buffer that is not working as it is intended to.

The buffer has to be replaced at the same time as when the catheter has to be replaced for it is not being cleaned with the washing solution during the regular washing procedure. This due to the fact that the buffer would take too much washing fluid to be cleaned within the washing process of the machine. However, with a few spare buffers the contaminated ones can be cleaned along with other medical instruments, which means the buffers can be re-used.

Future Improvements / Conclusion

To complete the urine analyzer there are still some improvements left for the future project group. The web interface needs to be improved due to the expectations of the hospital. Also the results need to be validated. To protect the patient data the interface needs to be secured. Our options are to make a special login or to make specific tablets. If you use tablets, the graphs need to be perfected. The points are too small to perfectly touch for results.

Also the data transfer can be improved by the future project group. Just skip the java step and let the microcontroller upload the data directly into the database. This will eliminate the need for a mini-pc which uploads the data. You can for example use a raspberry PI.

Regarding the device the future project group should make a new frame. This wooden frame is just for the prototype. They should also add a flow meter or volume meter which is accurate enough to measure all the urine automatically.

It’s also important to look into the possibilities of adding more sensors to the system, this will give a more accurate reading of the urine contents.

The database should automatically delete older entries. The data over 5 days old is not needed anymore, so it is not a problem to delete this. It is also necessary to add an fail safe to the system, to be sure you don’t lose your patient data.

For the future it might be a good option to connect the patient database of the hospital to the urine sensor database. This way more information will be available for the medical staff and you have less paperwork.