1. INTRODUCTION:

Electronic health (e-Health) uses digital information and communication technologies to improve the health care sector. The Mobile health (mHealth), a sub-segment of electronic health (e-Health) and the Global Observatory for e-Health¹ defined mHealth as “medical and public practice supported by the mobile devices, such as mobile phones, patient monitoring devices, personal digital assistants (PDAs), and other wireless devices”. mHealth involves the use and capitalization of mobile phone’s core utility of voice and short messaging service (SMS) as well as more complex functionalities and applications including general packet radio service (GPRS), third and fourth generation mobile communications (3G and 4G systems), global positioning system (GPS) and Bluetooth technology.

Furthermore, remote sensor installed in households or imaging device linked to mobile phones is often used to facilitate data transmission to the health service provider. This can reduce the patient’s need to visit heath care centre for check-ups.

Renal or kidney disease is one of the major health complications in the world². According to the world health rankings, about 40 countries in the world faces higher death rate and approximately 85 countries face moderate death rate due to renal diseases². World Health Report and Global Burden Disease (GBD) project stated that kidney and urinary tract related problems are important global burden diseases (GBD). According to these reports, every year approximately 850,000 people are dying and 1.5 million people are getting affected with the renal diseases. Hence, renal failure turns the 17^th leading cause of disability and 12^th leading cause of death^3,5,6. The renal related problems are detected and diagnosed at the end stage or a little earlier. After diagnosing, dialysis is one of the temporary solutions and is time-consuming continuous and prolonged process. The other therapeutic option for patients is renal replacement therapy (RRT), which is expensive and also relatively unavailable to the majority of patients. Hence, the earlier diagnosis of the preliminary stages of renal disease is essential to reduce the burden of end stage and to overcome the practical limitations of clinical treatment⁷.

Kidney diseases usually show minimum symptoms in its earlier stages. X-rays and ultrasound are some of the diagnostic methods are available to detect urinary diseases. The blood, urine and biopsy tests from kidney have been employed in the clinical examination to determine the kidney diseases. The limitations of these methods are invasive, time-consuming, and expensive, which also requires experienced operators to interpret the results and lack of continuous monitoring. To overcome these limitations, a better alternative method is exhaled breath analysis in which, the exhaled breath from normal as well as renal affected persons are compared and analyzed with various breath marking parameters. According to previous reports, ammonia, trimethylamine (TMA), dimethylamine (DMA), and monomethyl amine (MMA) are some important breath markers for renal disease^8,9. Among these, ammonia is significantly present at higher concentration levels, when compared with normal persons. The level of ammonia is 0.5 to 2 ppm for normal breath samples, whereas the level is > 2 ppm for renal disease affected breath samples^8,9. Davies et al¹⁰ have reported the mean concentration of ammonia in the breath of uremic patients and healthy individuals as 4.8 ppm (ranging from 0.8 to 14.7 ppm) and 0.9 ppm (with a range of 0.4 to 1.8 ppm).

There are different traditional methods available for breath gas / vapour detection which includes Solid Phase Microextraction-Gas chromatography-Mass spectrometry (SPME-GC-MS)¹¹, electrochemical sensors¹², laser technology¹³, Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS)¹⁴, Proton Transfer Reaction-Mass Spectrometry (PTR-MS)¹⁵, Infrared spectrometer¹⁶, Electronic nose¹⁷. Among all the above, Electronic nose (e-Nose) is a better alternative for traditional methods and it has many advantages which include a simple, economical, and portable method for the detection of ammonia. The metal oxide semiconductor-based sensing element is preferably in e-Nose due to its high chemical and thermodynamical stability. Paulsson et al.¹⁸ examined the detection of breath gas/vapour concentration using metal oxide based multisensory array and the results were validated through gas chromatography method. Moreover, different data evaluation techniques such as projection to latent structure (PLS) and artificial neural network (ANN) were applied. Jose Abraham et al.¹⁹ designed a compact wireless gas sensor using carbon nanotube/ PMMA thin film chemiresistor for the detection of various volatile organic compounds in which the output signals were observed in a personal computer.

In this work, we presented the design and experimental results of ammonia detection by chemiresistor method and its analysis through a smartphone. The detection principle is based on the changes in the electrical parameter of the sensing device due to the presence of ammonia vapor. The output data of the sensing device is transmitted to a mobile phone through Bluetooth module and the output signal of the device was displayed in the form of graphical user interface (GUI) on mobile screen through the developed Android application of Exhale Breath analyzer (EBA).

EXPERIMENITAL METHODS:

Ni-doped ZnO thin films were deposited on the glass substrates using home-build spray pyrolysis technique²⁰. The preparation method for precursor solution is as follows; 0.1 M of precursor salt as zinc acetate dihydrate (Zn(CH₃COO)₂·2H₂O, 99% purity, Sigma-Aldrich, Purity 99%) and 0.1M of dopant salt as nickel acetate tetra hydrate (Ni(CH₃COO)₂.4H₂O, Sigma-Aldrich, 98 % purity) were dissolved in 50 mL of deionized water. The fine mist of precursor solution was sprayed over the pre-heated glass substrates with the help of compressed dry air. The substrate temperature was measured with the help of microcontroller based thermostat supported with a thermocouple at an accuracy of ±1°C. The pyrolytic decomposition of the precursor solution takes place over the pre-heated glass substrate resulting Ni-doped ZnO thin films. The optimised spray deposition parameters are as given below, The pressure of compressed dry air is 2 kg/cm³, the substrate to spray nozzle distance is 30 cm, the spray gun positioning angle is 45°, precursor solution flow rate is 3 mL/min and the deposition temperature is 250° C. The spray time and successive spray interval were fixed at 5 s and 75 s for the proper growth of the film. After depositing, the films were annealed at 300° C for 120 minutes in the presence of oxygen to improve the crystalline quality of the film. The crystalline studies of the film were carried out using X-ray diffractometer (Bruker - D8 Focus XRD) with CuKα₁ (λ=1.5406 Å) radiation source. The surface morphology of the films was investigated using field-emission scanning electron microscope (JEOL - 6701F).

RESULTS AND DISCUSSION:

Structural studies and morphological studies:

The crystal structure and orientation of the spray deposited Ni-doped ZnO thin film were investigated by X-ray diffraction studies and is shown in Fig. 1. It shows that the prepared film is polycrystalline in nature with hexagonal wurtzite structure. The peak position are in good agreement with JCPDS card No: 36-1451 and are indexed to (100), (002), (101), (102), (110), (103) plane. The preferential plane was estimated using texture coefficient relation and the observed plane is (0 0 2). The crystallite size obtained from the preferred plane using well-known Scherrer formula was found to be 22 nm. Field-emission scanning electron micrograph shows a closely packed spherical shape smooth nanocrystalline with a size of 20 nm as shown in Fig. 2.

Device Construction:

The block diagram of developed Exhaled Breath Analyzer device is shown in Fig. 3. It comprised of a sensor module, microcontroller, Bluetooth module and an Android-based mobile phone. The sensor module comprises of a spray deposited Ni-doped ZnO thin films based sensing element and a signal conditioning circuit shown in the above figure. ATMEGA 32 microcontroller and HE05 Bluetooth module were utilised to process and to connect the sensor data to the mobile phone. An Android mobile displays the sensor output signal in the form of graphical user interface (GUI) in the developed Android application of “EBA” (Exhaled Breath Analyzer). Moreover, the obtained output data can be stored on the smartphone or secure digital (SD) memory card for further analysis.

Sensor module

↓

Microcontroller

↓

Bluetooth module

↓

Android mobile

Fig. 3: Block diagram of simple breath analyzer

The photographic view of developed breath analyzer device is shown in Fig. 4. The main components of the device are an MOS based sensing module, microcontroller, Bluetooth module, Android phone based mobile phone and power source. The sensing module comprises a metal oxide semiconductor-based sensing element and a signal conditioning circuit. A spray deposited Ni-doped ZnO thin film was used as a sensing element for the detection of ammonia vapor at ambient temperature. The electrical contacts were developed over the thin film surface using copper wire and silver epoxy. The signal conditioning circuit is used to filter the noisy signal. After the implementation of circuit connections, the ammonia vapor was blown onto the sensing element. In the absence and presence of ammonia vapor environment, the output voltages of the sensing device are monitored using the external measuring device. The sensor module is connected to the microcontroller unit, which converts the analogue output signal to digital signal. Finally, the microcontroller unit is an interface with a Bluetooth module, which is used to receive the wireless digital data and transmit to the mobile phone. In Android mobile phone, the EBA (Exhaled breath analysis) application is developed through Android Studio-Software Developing Kit (SDK) and JAVA coding. The Android mobile phone is used to monitor the sensing performance of the device.

Fig. 4: Photograph of Android mobile phone based ammonia breath analyzer device

Ammonia sensing studies:

Ammonia test:

The ammonia test confirmed the sensing behavior of developed breath analyser device. The device was allowed to reach equilibrium conditions by placing it in dry air environment which showed a stable baseline voltage. Then, the device is exposed in ammonia vapor environment, a sudden rise in voltage was observed, which indicates ammonia sensing response of the device. Upon returning to dry air conditions, the voltage value of the sensor element decreased and attained its baseline voltage, which represents the recovery behavior of the device. The changes observed in voltage with respect to time were measured for every 1 s; the change was visually observed on the smartphone screen in the developed “EBA” Android application. Further, ammonia sensing studies were repeated several times in order to confirm that the behavior of the device is reproducible.

The sensing performance of the developed breath analyzer device is based on the voltage changes in the presence and absence of the ammonia vapor. Hence, the threshold voltage value plays a significant role in ammonia vapors detection. The standard threshold value was fixed as 350 mV. In a dry air environment, the device reads a baseline value of 175 mV and the mobile screen consequently displayed the message, “ammonia is absent”. In an ammonia vapor environment, the device voltage increased the threshold value (>350 mV), and immediately the mobile screen displays the message, “ammonia is present”. Based on this threshold voltage value, the ammonia level (either low or high) can also be monitored using the developed application. By selecting the “Change View” option in an Android application, the ammonia identification, level of ammonia clearly displayed based on these visual representations of the sensor signal, one can easily analyze the ammonia content. Moreover, the obtained sensing data are also stored in the smart phone’s memory through the EBA application and are easily transferable to other computing devices such as mobiles, tabs, laptops, personal computers etc. Hence, the developed Android application and ammonia sensor device are simple, easy to handle and user-friendly. The logo of EBA (Exhaled Breath analyzer) Android application (see the white circle) is displayed in Fig. 5. (a) Output voltage changes in the absence and presence of ammonia vapour at different concentrations are shown in Fig. 5. (b) The obtained sensing data, which are stored in phone’s memory, are displayed as shown in Fig. 5. (c).

Ammonia sensing mechanism:

The metal oxide semiconductor-based gas sensors work on the basis of change in electrical conductance/resistance/voltage upon exposure to different reducing/oxidising gas/vapour atmosphere. The Ni-doped ZnO thin film based on sensor operated at ambient temperature. The molecular ionic oxygen species (O₂^-) dominant on the film surface up to 150°C. The oxygen molecules consume the electrons from the conduction band of metal oxide surface atoms and convert them to atomic oxygen species which is chemisorbed over the thin film surface ²¹. This oxidation reaction is conveyed as follows;

Conclusion:

A smart mobile phone based wireless ammonia sensor has been developed for analysing exhaled breath and the experimental results were evaluated. The developed device works on the basis of change in voltage of the nanostructured ZnO sensing element due to exposure to ammonia. The estimated ammonia sensing response value increases from 164 % to 584 % for 10 ppm and 50 ppm respectively. Furthermore, the prepared ZnO is high sensitive and selective to ammonia vapour at ambient condition. Thus, the preliminary work indicates that nanostructured ZnO thin film would be extended as an electronic nose (e-Nose) for diagnosing the renal disease.

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Received on 11.09.2017 Modified on 24.11.2017

Research J. Pharm. and Tech. 2018; 11(3): 841-846.

DOI: 10.5958/0974-360X.2018.00156.7