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  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 83 MEASUREMENT OF HUMAN BLOOD CLOTTING TIME USING LabVIEW Bharati. S R1 , Parvathi. C S2 and P. Bhaskar2 1 Department of Electroncs, Nutan Vidalaya Degree College, Gulbarga-585103, KA, INDIA 2 Department of Instrumentation Technology, Gulbarga University, P.G. Centre, RAICHUR-584133, KA INDIA ABSTRACT This paper focuses on development of a system where the human blood clotting time of is determined by measuring the blood conductivity during coagulation. The minimum amount of blood sample (1ml) is taken and conductivity cell is immersed into it. The signal produced by conductivity cell will be in terms of millivolts which is further signal conditioned and acquired by the onchip ADC of ATMEGA 328 microcontroller. This voltage is converted into corresponding conductivity by curve fitting methodin microcntroller. The conductivity thus measured is transmitted to PC through USB. Graphical user interface (GUI) is developed using LabVIEW software. Further LabVIEW plots the graph of variation of conductivity with respect to time. From the graph, the clotting time is determined when conductivity becomes almost constant and the same is displayed on the front panel of the PC. The proposed device has advantages of portability, easy operation and real time results for monitoring in the healthcare units. The results thus obtained from proposed device is correlated against clinical test and found efficient and accurate. Keywords: Blood Coagulation, ATMEGA328, Clotting Time, LabVIEW. 1. INTRODUCTION The human blood is composed of cells distributed in an aqueous solution. Many charged or polar molecules are present at both inside and outside the blood cells. Numerous inorganic ions are distributed through the blood volume. Hence it is a good conductor. And we can measure the conductivity by feeding small sinusoid amplitude [1]. Blood coagulation is one of the haemostatic processes of humans, which consists of a complex, physiological cascade. When the blood vessel is damaged, the substances released from the destroyed endothelium into blood induce formation of a platelet aggregation at first[2,3]. After activation, platelets tend to adhere to the damaged vessel wall and finally, an aggregated platelet plug INTERNATIONAL JOURNAL OF ELECTRONICS AND COMMUNICATION ENGINEERING & TECHNOLOGY (IJECET) ISSN 0976 – 6464(Print) ISSN 0976 – 6472(Online) Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME: www.iaeme.com/ijecet.asp Journal Impact Factor (2014): 3.7215 (Calculated by GISI) www.jifactor.com IJECET © I A E M E
  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 84 is formed to prevent the loss of blood. During this process, plasma clotting also happens. When the cells are placed in endothelium are exposed to blood, the plasma clotting, known as blood coagulation, is activated. Blood coagulation process has more complex cascade, which consists of enzymatic reactions in blood plasma [4]. As a result of complicated process, polymerized fibrin is formed from fibrinogen to prevent the loss of blood cells. It is important to monitor blood coagulation process because disorders in coagulation can lead to higher risk of bleeding. Also, blood coagulation disorders have possibilities to bring pathological complications in increasing thrombosis and embolism in the vascular system[5]. These are life-threatening, which can induce fatal danger in various clinical circumstances, such as cardiac surgery [6]. Therefore, it is essential to check the blood coagulation process regularly to allow the detection of clotting problems. Clinical laboratory examination of blood coagulation analysis allows observation of the amount of vitamin K in the blood indirectly and diagnosis of liver disorder. The treatment of drugs used in some hereditary and hemorrhagic diseases depends on the process of blood coagulation by measuring the clotting time or prothrombin time [7]. The coagulation of blood is a complex process during which solid clots are formed in the blood. The conversion of fibrinogen into fibrin and the subsequent covalent cross-linking of fibrin play important roles in this process, and can be induced by an imbalance between coagulant and anticoagulant factors. Although coagulating blood is vital to the preservation of life, blood clots can impede blood flow in the vessels. Thrombus formation is responsible for most heart attacks and strokes and complicates other pathological conditions such as coronary thrombosis, peripheral deep venous thrombosis, and pulmonary embolus, and can eventually cause death unless brought under control [8]. In addition, paralytic patients confined to bed usually suffer from intravascular clots due to coagulation that tends to occur when the flowing blood is obstructed for a few hours in any vessel of the body. Therefore, a clear understanding of blood coagulation properties is crucial for clinical diagnosis, and techniques for detecting blood coagulation need to be developed. A common method to assess the process of blood coagulation involves adding blood to three or four test tubes and then tilting the tubes at 30-s intervals until the blood can no longer flow. Clotting time is used as a screening test to measure all stages in the intrinsic coagulation system and to monitor heparin therapy [9]. LabVIEW is visual programming software developed by National Instruments. LabVIEW is an acronym for Laboratory Virtual Instrumentation Engineering Workbench. It is used in testing, automation, instrument control, and monitoring and data acquisition. Programming is done by connecting icons together to form a visual flow chart of processes. There is no code or syntax to memorize or acronyms to learn. Programming is like drawing a flowchart [10]. LabVIEW is growing in popularity. LabVIEW is completely graphical in its programming and visualization of the data and controls [11]. The program that we create is called VI the Virtual Instrument. Within this VI there are two screens. The front panel is the GUI (Graphical User Interface) where the human interacts and monitors the program while it is running. The front panel contains the voltage readings and the measurements etc. The block diagram contains the programming working behind the front panel. Just like wires, switches and circuits would work behind an instrument panel. The block diagram is icons wired visually together to create a flowchart of the program. Icons represent the functions of what is being controlled and wires contain the data that connects the icons together [12]. The present work utilizes LabVIEW 12.0 version. Literature survey on measurement of human blood clotting time reveals that many researchers re have done measurement using different techniques. George S Sutton has done measurement using Lee & White method [13]. Hyunjung Lim et al have done measurement using Light Transmission method where co-agulation of blood is measured by intensity of the light transmitted [14]. Robert A Schneider et al have done measurement by observing viscosity of blood
  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 85 during Coagulation [15]. Chih-Chung Huang et al, have studied the coagulation by Ultrasound Elastography Method [16]. The measurement methods as mentioned above authors are found to be time consuming and complex. This motivated us to design an instrument to measure human blood clotting time by measuring electrical conductivity which is found to be fast and easy compared with conventional analysis techniques. This work is valuable for the development of clinical equipment for routine coagulation tests. 2. HARDWARE DETAILS In this manuscript, we present a new blood coagulation monitoring method using LabVIEW. Fig. 1 shows the block diagram of the microcontroller based human blood conductivity measurement system. Fig 1. Block diagram of human blood clotting time measurement system It consists of • Conductivity cell • Signal conditioning circuit • Microcontroller • PC The complete schematic diagram of Atmel microcontroller based human blood conductivity measurement system is shown in figure 2. Microcontroller ADC SerialPort Sine wave Generator (1Khz) R R R C Instrumentati on Technology AmplifierRectifier and filter PersonalComputer LabView Monitor Keyboard
  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 86 Fig 2. Schematic diagram of human blood clotting time measurement system i. Conductivity Cell The conductivity cell consists of a pair of electrodes that are firmly located in a constant geometry. The cell used in the present study consists of two platinum electrodes of 1 cm2 cross sectional area that are separated by a distance of 1 cm. the cell constant of the cell used in the present study is 1.01. [Elico manual] ii. Signal Conditioning Circuit The proposed signal conditioning circuit is designed for this particular application which utilizes AC conductivity measurement. This circuit consists of a stable sine wave oscillator constructed by using an operational-amplifier {WEIN-BRIDGE OSCILLATOR}. This oscillator is designed to generate a sine wave frequency equal to 1 KHz at amplitude equal to nearly 10 VPP. The generated AC sine wave is used as an excitation source for the impedance bridge containing a sample in one of the bridge arm. The AC excitation source is capacitively coupled or coupled through the capacitor to the bridge. The differential voltage is amplified using differential amplifier designed by using an operational amplifier. The differential gain can be varied from 1 to 10. The amplified differential output is further amplified by another with maximum gain of 10, thus amplified AC voltage is rectified and filtered to get the average DC voltage, corresponding to the conductivity of the blood sample. This analog output is converted to 10 bit digital data by using an ADC which is inbuilt in the microcontroller which is being used. iii. Microcontroller In present system ATMEG 328 microcontroller is used. This microcontroller is a high- performance Atmel 8-bit AVR RISC-based microcontroller combines 32KB ISP flash memory with read-while-write capabilities, 1KB EEPROM, 2KB SRAM, 23 general purpose I/O lines, 32 general purpose working registers, three flexible timer/counters with compare modes, internal and external interrupts, serial programmable USART, a byte-oriented 2-wire serial interface, SPI serial port, 6- channel 10-bit A/D converter (8-channels in TQFP and QFN/MLF packages), programmable
  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 87 watchdog timer with internal oscillator, and five software selectable power saving modes. The device operates between 1.8-5.5 volts. 3. SOFTWARE DETAILS The program to acquire the data and to process is written in embedded C languagefor microcontroller.. The detailed flow chart is shown in figure 3. The conductivity measurement of the blood can be impacted by various criterions. One among them would be the curve fitting method. Finally the data is processed using the relation y= mX+C to get the result of the conductivity where y is voltage acquired by the ADC, X is conductivity of blood , m is slope and C is intercept. The equivalent conductivity is calculated for each voltage variation. The result thus obtained is transmitted to PC through USB where the LabVIEW is used for determining clotting time. A GUI has been designed in LabVIEW for the user sake i.e. for the display of the result such as clotting time. Figure 4 shows the designed GUI where the information about results can be viewed. A GUI program is a graphical based approach to execute the program in a more user friendly way. It contains components with proper labels for easy understanding to a less experienced user. These components help the user to easily understand how to execute or what to do to execute the program. When an user responds to a GUI’s components by pressing a pushbutton or clicking a check box or radio button or by entering some text using text box, the program reads the necessary information for that particular event, hence GUI programs are also known as event driven programs. Fig:3 Detailed flowchart for measurement of conductivity using microcontroller
  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 88 Fig 4 and Fig 5 show the block diagram of the VI designed to plot the graph of variation of conductivity with respect to time and display of clotting time on the front panel. Fig 4. VI Block diagram for measurement of conductivity Fig 5. VI Block diagram for measurement of clotting time.
  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 89 The LabVIEW program is written to acquire the data, to process, to measure and to display the clotting time on the front panel. The data analysis file is to be kept in the required format and placed in the a subdirectory. This file path is to be given to the path reference to read. All the variables such as convert data array, conductivity versus time, array length, clotting time, min and max values etc are to be initialized for default values or zero. Infinite while loop is executed with time delay so that other applications need time from cpu to work in multitasking mode and also to enable the polling of other functions. As the program has to be fit in the same screen stacked sequence is used which will also make debugging and any modifications simpler. When the program is running, inside the while loop the various inputs are continuously polled for the relevant input. The buttons which are polled are Read Data File and Plot buttons. The file path is to be entered to read the data file. During polling, pressing the read button, the raw data is read and converted to the tab separated string format for further processing. The data are further separated and put into two dimensional array as conductivity in one column and time in another column. Then string formatted array is converted to floating decimal number array which is required for plotting. By pressing the plot button, the 2D array is transposed and graph is plotted as conductivity vs time in the front panel. It will also find the total size of the array which is required for differentiation. Differential equation is applied for clot conductivity values versus time to find where the clot conductivity values remain constant. After finding the duration of the clotting time in seconds, which in turn is expressed in terms of minute and displayed on the front panel. Again the polling will continue for the next data set from different file to be input. This process will continue till we terminate the program. Fig 6 shows the front panel of GUI where we can see the display of clotting time. The detailed flowchart for measurement of conductivity and display of clotting time is shown in fig 7. Fig 6. Front panel of LabView showing clotting time
  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 90 4. RESULTS AND DISCUSSION Fig 8 shows the graphical representation of variation of actual conductivity with respect to time. It is clear from the plot that the conductivity decreases as time elapses due to disappearance of conductive ions. Once the blood is clotted, conductivity reduces to great deal and becomes almost constant. Fig 7. Flow chart Initialization of constants and variables Input path for data file Start Is button pressed? Read data and display Convert data into 2 dimensional array Is button pressed? Convert string array to floating array Plot graph time Vs conductivity Fine array size Find out constant dx/df Conductivity Find total duration Convert to minute and display Next set of data No Yes No Yes
  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 91 Fig 8. Variation of conductivity with respect to time The designed Instrument is subjected to measure the clotting time of 20 individuals. Fig 9 shows the clotting time of each individual measured by the instrument developed and also compared with the clinical measurements and found that there is 96% of accuracy. The normal range of time for the blood clotting is 5 to 15 min. Fig9. Results of testing Sample 5. CONCLUSION This work demonstrates the development of a system that allows precise detection of the coagulation time of whole blood by measuring conductivity during coagulation using LabVIEW. The method is shown to be useful for determination of the blood disorders like lack of hemoglobin, hemophilia, and hematocrit etc., Clotting time is used as a screening test to measure all stages in the intrinsic coagulation system and to monitor heparin therapy during major surgeries. In this work, analysis of the conductance change of blood sample during coagulation was conducted successfully and results showed that the clotting time measurement using LabVIEW is a sensitive and promising technique for monitoring blood coagulation process. This method found to be fast and easy measurement compared with other conventional analysis techniques. This work is found valuable for the development of clinical equipment for routine coagulation tests.
  • International Journal of Electronics and Communication Engineering & Technology (IJECET), ISSN 0976 – 6464(Print), ISSN 0976 – 6472(Online), Volume 5, Issue 2, February (2014), pp. 83-92 © IAEME 92 REFERENCES [1] Chia-Chern Chen, “Electric Impedance and Coagulation time measure of human whole Blood”, Institute of Micro-Electro-Mechanical System. National Cheng Kung University, Tainan, pp .456-472 June 2005. [2] Rodvien, R. and C. Mielke Jr, “Role of platelets in hemostasis and thrombosis”, Western Journal of Medicine”, The BMJ Publishing Group, England, pp. 181-187 1976. [3] Nigel Mackman, Rachel E. Tilley, and Nigel S. Key, “Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis, Arteriosclerosis, Thrombosis, Vascular Biology”, Lippincott Williams & Wilkins, U.S.A., pp. 1687-1691, 2007. [4] James P. Riddel Jr, Bradley E. Aouizerat, Christine Miaskowski, and David P. Lillicrap, “Theories of Blood Coagulation”, Journal of Pediatric Oncology Nursing, SAGE Publications, U.S.A., pp. 123-131, 2007. [5] Paula HB, Bolton-Maggs,” The rare coagulation disorders, Review with guidelines for Manage-5”, World Federation of Hemophilia, Canada, pp. 1000-1001, (2006). [6] Parwis Massoudy, Sü;rreya M. Cetin, Matthias Thielmann, P. Kienbaum, Jarowit A.Piotrowski, Gü;nter Marggraf, Christof Specker, and Heinz Jakob,” Antiphospholipidsyndrome in cardiac surgery--an underestimated coagulation disorder?”, European Journal of Cardio-Thoracic Surgery, European Association for Cardio-thoracic Surgery, The Netherlands, pp. 133-139,2000. [7] G. Murano and R. L. Bick, “Basic Concepts of Hemostasis and Thrombosis”, Boca Raton, FL: CRC Press, pp.124-131 1980. [8] D. J. Kuter and R. D. Rosenberg, “Hemorrhagic Disorders III. Disorders of Hemostasis” in: W. S.Beck (Ed.), Hematology, 5thed. Cambridge, MA:MIT Press, pp. 577-598,1991. [9] J. M. Thomson, “Blood Coagulation and Haemostasis”, New York: Churchill Livingstone, pp .674-685 1991. [10] https://www.google.co.in/ richfatcat.hubpages.com [11] https://www.google.co.in/www.NI.com [12] Course Manual, LabVIEW Basics, By National Instruments. [13] George C Sutton, “Studies on blood coagulation and the effect of Digitalis”, circulation Journal of the American Heart Association. ISSN: 1524-1539. [14] Hyunjung Lim, Jeonghun Nam, Youngjin Lee, Shubin Xue, Seok Chung and Sehyun Shin”, Blood Coagulation Study Using Light – Transmission Method”, Korea University, Korea, vol-46, issue – 9, pp. 553 – 555.2006 [15] Robert A Schnider, M.D. and Violet M. Zangari, B.S. Variations in clotting time, Relative Viscosity and other Physiochemical Properties of the Blood Accompanying Physical and Emotional Stress in the Normotensive and Hypertensive Subject. Psychosomatic Medicine., vol 13, no. 5, pp.289-303. September 1, 1951 [16] Chih-Chung Huang, Yi-Hsun Lin, Ting-Yu Liu, Po-Yang Lee, Shyh-Hau Wang, Study of the Blood Coagulation by Ultrasound Journal of Medical and Biological Engineering, pp. 31(2): 79-86. 31, Mar 2011. [17] Chandrika V, Parvathi C.S. and P. Bhaskar, “Design and Development of Pulmonary Tuberculosis Diagnosing System using Image Processing Techniques and Artificial Neural Network in Matlab”, International Journal of Electronics and Communication Engineering &Technology (IJECET), Volume 4, Issue 2, 2013, pp. 357 - 372, ISSN Print: 0976- 6464, ISSN Online: 0976 –6472.