Development of Biomedical Devices in Africa for Africa: A Blood Glucose Meter

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1 International Journal of Electrical and Electronic Science 2015; 2(4): Published online February 15, 2016 ( ISSN: Development of Biomedical Devices in Africa for Africa: A Blood Glucose Meter A. R. Zubair 1, *, C. O. Adebayo 1, E. U. Ebere-Dinnie 1, A. O. Coker 2 1 Electrical/Electronic Engineering Department, Faculty of Technology, University of Ibadan, Ibadan, Nigeria 2 Civil Engineering Department, Faculty of Technology, University of Ibadan, Ibadan, Nigeria address ar.zubair@yahoo.co.uk (A. R. Zubair) Keywords Biomedical Devices, Diabetes Management, Self-monitoring, Blood Glucose Meter, Medical Technology Transfer Received: December 30, 2015 Revised: January 14, 2016 Accepted: January 16, 2016 Citation A. R. Zubair, C. O. Adebayo, E. U. Ebere-Dinnie, A. O. Coker. Development of Biomedical Devices in Africa for Africa: A Blood Glucose Meter. International Journal of Electrical and Electronic Science. Vol. 2, No. 4, 2015, pp Abstract Diabetes is a chronic disease characterised by high levels of glucose in the blood. A blood glucose meter is an electronic device for checking the level of glucose in the blood. Although the meter helps people monitor their condition, diabetes management is generally expensive. It is necessary to improve self-monitoring of blood glucose in Nigeria in particular and Africa in general by local design and production of blood glucose meters without compromising on accuracy and precision. The design and construction of a blood glucose meter with audio-visual output and computer interface is presented. The accuracy of the locally constructed blood glucose meter compared with an imported blood glucose meter was found to be within tolerable range of ± 3.17%. 1. Introduction Diabetes is a chronic disease characterised by high levels of glucose in the blood [1, 2, 3, 4, 5, 6, 7]. Blood glucose levels are controlled by insulin, a hormone produced by the pancreas. Diabetes occurs when the pancreas is unable to produce enough insulin, or the body becomes resistant to insulin, or both [1]. There are two major types of diabetes, type 1 and type 2. Type 1 diabetes is an auto-immune disease where the body's immune system attacks the insulin producing cells of the pancreas. People with type 1 diabetes cannot produce insulin and require lifelong insulin injections for survival [1]. Without insulin, the body cannot convert glucose into energy and instead burns its own fat as a substitute. Unless treated with insulin, people with type 1 diabetes will accumulate dangerous chemicals in their blood from the burning of fat, causing a condition known as ketoacidosis. This condition is potentially life-threatening if not treated. Type 2 diabetes is where an individual s body does not properly use insulin combined with a relative insulin shortage within the body. It is associated with hereditary factors and lifestyle risk factors including poor diet, insufficient physical activity and overweight or obesity [2]. Insulin is a hormone produced in the human body which is needed for the conversion of sugar, starches, and other food into energy. Without insulin or if insulin production or action are ineffective, the body cannot turn glucose into energy and results in glucose remaining in the blood, causing blood glucose levels to become high. This can result in a number of complications, including serious damage to the nerves and blood vessels [6]. Hyperglycaemia or high blood sugar is a condition in which an excessive amount of glucose circulates in the blood plasma. It refers to chronically high blood glucose levels.

2 103 A. R. Zubair et al.: Development of Biomedical Devices in Africa for Africa: A Blood Glucose Meter This is generally a blood glucose level of 10 mmol/l (180 mg/dl) and above. Hypoglycaemia refers to dangerously low blood glucose levels that drop below 70 mg/dl. It is an acute complication of diabetes and occurs in individuals who use insulin or specific kinds of oral diabetes medication. Glucose meters today are small, portable, and easy to use. A blood glucose meter is an electronic device for checking the level of glucose in the blood. It is very helpful for those suffering from diabetes since very small quantity of blood is needed for the test to be performed, provided the patients carefully follow the instructions for the testing procedures. Self-monitoring task made possible and simple for patients will ease the numerous tasks of medical staff [7]. A single blood drop is made to come in contact with a disposable test strip connecting a digital meter. Within a few seconds, the reading of blood glucose level appears on the digital display. The mark of a good meter is one that the patient will use regularly and that returns accurate and precise results. This crucial device for diabetics has emerged and progressed in three decades. Over the past few years the trend with blood glucose meters has been to maximize patient comfort and convenience by reducing the volume of the blood sample required. Judging from the many complications associated with diabetes, there is a need for constant and up-to-date check of blood sugar level in the body. Of all the available life-long treatments for sustaining diabetic patients, the blood glucose meter has proven to be the most efficient and reliable, as it allows for regular monitoring of blood glucose levels, thus preventing the risk of falling into insulin shock and other very serious complications. Although the meter helps people maintain their condition, diabetes management is generally expensive. It is necessary to improve self-monitoring of blood glucose in Nigeria in particular and Africa in general by local design and production of blood glucose meters without compromising on accuracy and precision [3, 4, 5]. To achieve the Millennium Development Goal of Health for All, it is necessary to increase the availability of biomedical devices in Africa [8, 9, 10, 11]. The design and construction of a low cost blood glucose meter with locally available raw materials and components is discussed. The meter has necessary electronic signal acquisition and processing units, visual output display, audio output speaker and computer interface for storage and comparison of outputs over time [12, 13, 14, 15, 16]. 2. Materials and Methods 2.1. Test Strip The proposed meter is designed to use commercial test strips designed for the One Touch Ultra glucose meter made by Lifescan. The glucose concentration in a whole blood sample is measured amperometrically. The glucose sensor is an electrochemical diagnostic strip which uses glucose oxidase enzymes in conjunction with three electrically conductive electrodes. This approach is useful when using amperometric sensors due to the reliability of measuring voltage and current in the same chemical reaction. The glucose oxides are immobilized in a platinized activated carbon electrode. The sensor is composed of three electrodes: a glucose oxide membrane layer, a polyurethane film that is permeable by the glucose, oxygen, and hydrogen peroxide. Amperometry measures electric current between a pair of electrodes that are driving the electrolysis reaction. Oxygen diffuses through the membrane. As soon as the enzyme recognizes the glucose molecules, it acts as a catalyst to produce gluconic acid and hydrogen peroxide from glucose and oxygen as illustrated in Fig. 1. Figure 1. Electrode reaction. It is important to highlight that the expressed relationship in the equation is linear. This is different in reality since other biochemical substances might be involved in the reaction as well. The electrode recognizes the number of electron transfer due to hydrogen peroxide/oxygen coupling. This electron (current) flow is proportional to the number of glucose molecules present in blood, thereby giving the glucose concentration. The output of the sensor (system of electrodes) is further processed by signal conditioning circuits, a PIC16F877A microcontroller and the result is displayed on the Liquid Crystal Display (LCD) and also played on a speaker. The speaker helps to accommodate diabetics whose sight has been significantly impaired by the condition Hardware Design Fig. 2 illustrates the block diagram of the Glucose Meter hardware design. This contains all the necessary electronic parts for signal amplification, digitization, and display of the blood glucose measurement on the LCD screen and also via a speaker. An interface module (TTL to USB) is integrated with the device to allow for data processing. The Meter is designed to be portable and battery powered. The power for the components is delivered from two 9 Volt batteries connected to two voltage regulators, one for +5 Volts, the other for -5 Volts. A PIC16F877A microprocessor is the central processing unit of the meter. The microprocessor also

3 International Journal of Electrical and Electronic Science 2015; 2(4): performs Analog to Digital Conversion (ADC). The glucose measurement circuit includes three TL072 Operational Amplifiers (Op Amp.s), a 4052 Analog switch, and a Zener Diode. The Op Amps serve as current to volage converters. The instructions and measurements are displayed on a 16x2 character Liquid Crystal Display (LCD) unit. The measured blood glucose concentration value is converted back to analog form by a Digital to Analog Converter (DAC), before being played via a speaker. An M24C512 EEPROM is prestored with audio samples of 0 to 10 and mg/dl. The complete circuit of the blood glucose meter designed and constructed in this work is shown in Fig. 3. sample is applied. A potential of -400 mv is applied between Electrode 1 and Electrode 3 of Fig. 4. This voltage difference is required to initiate the redox reaction on the test strip. The glucose measurement originates as a small current generated by the chemical reaction occurring in the test strip. The redox reaction breaks down the glucose and releases electrons. The flow of electrons is known as current and is collected by electrodes built-in to the test strip. The current produced from the test strip comes from Electrode 3 and connects to the inverting input of the Operational Amplifier (used as a transimpedance amplifier) where it is converted to voltage. The Op Amp is used as a high impedance source that forces all of the current to flow through the resistor, thus amplifying the incoming signal. The resulting voltage is output at Electrode 1 where it goes to the filter. Another potential is applied to detect when a test strip is inserted Signal Processing: Microcontroller and Analog-to-Digital Conversion Figure 2. Block Diagram of the Blood Glucose Meter Detection and Amplification The glucose detection circuit includes the current-tovoltage converter and the 100 Hz low pass Butterworth filter. The glucose test strip is connected to the circuit and blood The microcontroller is responsible for the 10-bit Analogto-Digital conversion (ADC) and LCD control and uses a 20 MHz clock. The resolution is controlled by the number of bits of the ADC and the voltage reference. Bit Range = 2 10 = The digital counts are related to the input voltage through the use of a reference voltage. The reference voltage (V ref ) used in the meter is 5 Volt. Eqn. (1) is the expression for the voltage resolution [16]. V ref 5 Voltage Res olution = = = Volts (1) Range 1024 Figure 3. Circuit Diagram of Blood Glucose Meter (Hardware).

4 105 A. R. Zubair et al.: Development of Biomedical Devices in Africa for Africa: A Blood Glucose Meter Table 2. Pre-recalibration measurement readings obtained with locally constructed meter and imported meter. Figure 4. Test Strip. The glucose measurement is taken from a single acquisition from the ADC. When a sample is applied to the test strip, the voltage jumps to a peak value and then begins to decay linearly between 1 and 5 seconds. The voltage reading is taken 4 seconds after the sample is applied. A typical voltage curve for glucose is shown in Fig. 5. Local Local An average difference of 90 mg/dl was discovered between the two meters and this was used to recalibrate Eqn. 2 to obtain corrected glucose concentration - voltage relationship of Eqn. 3. GC = x V (3) Figure 3. Typical Glucose Voltage Curve. The voltage level V is then converted to blood glucose concentration GC. The relationship between V and GC was determined experimentally. Fifteen test measurements shown in Table 1 and Fig. 6 were taken over a range of glucose concentrations ( mg/dl). A line of best fit was drawn as shown in Fig. 6. The slope and intercept of this line gives glucose concentration - voltage relationship as: GC = x V (2) Table 1. Glucose Concentration -Voltage Relationship. V (V) GC V (V) GC Recalibration Twenty-Two blood samples with a defined distribution of blood glucose concentration from mg/dl from patients were used for calibration purpose. The subjects were between the ages of 13 and 60 years. The locally constructed blood glucose meter and an existing imported One Touch Ultra blood glucose meter were used to measure these blood samples. The readings of the two meters are presented in Table Computer Interface The microcontroller is programmed to store up to 30 past measurement results. A TTL to USB module is connected to the microcontroller to interface the meter with a Digital Computer to harvest and back up the measurement results stored on the microcontroller. The harvested results can be aggregated and plotted as illustrated in Fig. 7. The response of a diabetic to treatment can be assessed with the aid of such harvested results and graph. GC Voltage Figure 4. Glucose Concentration - Voltage Relationship (Best Fit Line).

5 International Journal of Electrical and Electronic Science 2015; 2(4): Software Implementation Figure 7. Graph of stored meter readings. Fig. 8 shows the flow chart for the associated software implementation with regard to the microcontroller. Figure 5. Flow Chart of the Associated Software. 3. Results and Discussion After the recalibration exercise, the locally constructed blood glucose meter was again tested with another set of twenty-two blood samples and its performance is found comparable with the performance of the existing imported One Touch Ultra blood glucose meter as illustrated in Table 3 and Fig. 9.

6 107 A. R. Zubair et al.: Development of Biomedical Devices in Africa for Africa: A Blood Glucose Meter Table 3. Post recalibration test results obtained with locally constructed meter and imported meter. Local Local Meter GC programmes for the Development of Innovative Interdisciplinary Biomedical Engineering Programs in Africa organised by Northwestern University (NU), Chicago, USA in collaboration with University of Cape Town (UCT), Cape Town, South Africa, University of Ibadan (UI), Ibadan, Nigeria and University of Lagos (UNILAG), Lagos, Nigeria under United States National Institutes of Health Grant No 1D43TW References [1] World Health Organisation, (2012). Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. WHO/NCD/NCS/99.2. [2] Shaw, J., Chisholm, D. (2003). Epidermology and Prevention of Type 2 Diabetes and the Metabolic Syndrome. MJA. 179: pp [3] International Diabetes Federation, (2006). Facts and Figures: Prevalence. [Accessed February 14, 2014] [4] Whiting, D. R., Guariguata, L. Weil, C., Shaw, J. (2011). IDF Diabetes Atlas: Global estimates of the prevalence of diabetes for 2011 and Diabetes Research and Clinical Practice Vol. 94, No. 3, pp [5] Ogbera, A.O., Ekpebegh, C. (2014). Diabetes mellitus in Nigeria: The past, present and future. World J Diabetes Vol. 5, No. 6, pp Figure 9. Comparison of the Performance of Locally Constructed Blood Glucose Meter with that of the Existing One Touch Ultra Blood Glucose Meter. The constructed blood glucose meter presents acceptable accuracy for a prototype. It is shown here that the accuracy of the constructed blood glucose meter compared to the existing imported One Touch Ultra blood glucose meter is approximately ± 3.17%. The Food and Drug Administration stipulates that a device s measurements must fall within a range of ± 20%. The tests performed show that the constructed blood glucose meter is well within the FDA requirements. 4. Conclusions The performance of the locally constructed blood glucose meter is satisfactory. The accuracy of the meter in comparison with an imported meter is well within the United State of America s Food and Drug Administration (FDA) requirements. Thus, the meter can be used in lieu of imported meters for diabetes management. The device is portable, rugged, affordable and with low energy consumption. Acknowledgement The authors of this work benefitted from the training [6] Australian Institute of Health and Welfare, (2008). Diabetes: Australian Facts. Cat no. CVD [Accessed February 14, 2014] [7] Lekoubou, A., Awah P., Fezeu, L., Sobngwi, E., Kengne, A. P. (2010). Hypertension, Diabetes Mellitus and Task Shifting in Their Management in Sub-Saharan Africa. International Journal of Environmental Research and Public Health. Vol. 7, No. 2, pp [8] Zubair, A. R. (2010). Biomedical Instruments: safety, quality control, maintenance, prospects & benefits of African Technology. African Journal of Medicine and Medical Sciences, Afri. J. Med. med. Sci. (2010) 39, Suppl [9] Malkin, R. A. (2007). Design of Health Care Technologies for the Developing World. Annual Review of Biomedical Engineering. Vol. 9, pp [10] Peña-Mohr, J. (1987) Distributing and Transferring Medical Technology. International Journal of Technology Assessment in Health Care Vol. 3, No. 2, pp [11] IAEA (2000). Handbook on Care, Handling and Protection of Nuclear Medicine Instruments. A publication of the International Atomic Energy Agency (IAEA), Vienna. [12] Theraja, B.L., Theraja, A. K. (2005). A Textbook of Electrical Technology, S. Chand & Company ltd, New Delhi. [13] Brown, J.M., and J.O. Carr, J.O. (1981). Introduction to Biomedical Equipment Technology, John Wiley & Sons, New York. [14] R.S. Khandpur, R. S. (1987). Handbook of Biomedical Instrumentation, McGraw-Hill, New Delhi.

7 International Journal of Electrical and Electronic Science 2015; 2(4): [15] Martin, J., Norris, B., Murphy, E., & Crowe, J. (2008). Medical Device Development: The Challenge for Ergonomics. Applied Ergonomics, Vol. 39, No. 3, pp [16] Athinarayanan, R. Microcontroller Based Temperature Measurement with Software Linearization, Department of Technology Northern Illinois University DeKalb, IL U.S.A. Available at [Accessed February 14, 2014].