Theses & Dissertations

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https://hdl.handle.net/20.500.14170/2003

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Browsing Theses & Dissertations by Department "Universiti Malaysia Perlis"
  • Publication
    Development of silicon nanowire lab-on-chip microfluidics integrated biosensor for low concentration bio-molecules detection
    ( 2015)
    Tijjani Adam
    Lab-on-chip fabricated with one-dimensional nanowires offer excellent electrical properties where bio molecular analysis at very low concentrations is becoming increasingly relevant for medical and research communities. Good number of techniques and promising results has been established for detecting small concentrations; however, for high-throughput measurements and label-free detection are still area of fresh investigation. Many research groups have reported high level of bio recognition by using semiconductor nanowire. The semiconductors silicon nanowire biosensor utilizes a Nano wire between two conducting materials. The nanowire has its atoms concentrated on its surface. Thus, any small changes in the charges present on the nanowire will cause a change in the flow of current. In this thesis, a simulation study coupled with experimental approach to explain the change in wire surface behavior as function of the surface charge. The linear behavior of the conductivity to increase the sensitivity of a semiconducting nanowire biosensor is ascertained. The silicon wire should be between 5 to 20nm to allow mean distance between atoms, the oxide should be as thin as possible for optimum surface integrity, and the functional layer should be thin and have a high dielectric constant. The ionic concentration of the electrolyte should be kept low in order to have a large Debye screening length. To confirm these theoretical results, Silicon nanowire of ≈ 15nm was fabricated using conventional photolithography coupled with dry etching process. To determine the capability of the device, it subjected to various pH values and to achieve this, the device is being operated based on the principle of Field Effect Transistor (FET). The surface of the device is hole dominated (p-type material).
      6  11
  • Publication
    Electrical label-free sensing of cardiac troponin biomarker: FET-based integration with substrate-gate coupling
    ( 2017)
    Mohamad Faris Mohamad Fathil
    Acute myocardial infarction (AMI) is a leading cause of death worldwide despite the existence of therapy’s advances. Therefore, an early diagnosis method by using cardiac biomarkers is essential to enable correct countermeasures. Cardiac Troponin I (cTnI) is one of the cardiac biomarkers for early diagnosis of AMI and considered as ‘gold standard’ for cardiac muscle injury determination. The detection of cTnI through an electrical-based biosensor allows label-free detection by converting biomolecular binding event into a significant electrical signal via a semiconductor transducer. It utilizes conductivity to specify the existence of biomolecules. One of the electrical-based biosensors known as field-effect transistor (FET)-based biosensor has drawn much attention for owning the concept of charge transduction; thus, allows early, high sensitivity, high selectivity, and rapid diagnosis of the specific cardiac biomarker at low concentrations. In this work, the zinc oxide (ZnO)-FET biosensor coupled with substrategate has been designed and fabricated for the detection of cTnI biomarker. ZnO thin film, as n-type biocompatible semiconductor material, and also as transducer was deposited via sol-gel and spin coating techniques between p-type source and drain terminal on SOI substrate, forming a p-n-p junction, a device capable of bio-sensing application. The surface morphology of the thin film was characterized by using atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM). The thin film, which demonstrated hexagonal wurtzite phase as shown by X-ray diffraction (XRD) analysis appropriate for biomolecules interaction. The surface of the ZnO thin film was immobilized with cTnI monoclonal antibody (MAb-cTnI) as biological receptor via covalent binding technique for capturing cTnI biomarker. The process was validated by Fourier transform-infrared (FTIR) and X-ray photoelectron spectroscopy (XPS). The device structure was simulated in Silvaco Atlas 2D-simulator, to elucidate its electrical characteristic, by means of hole and electron concentration in the channel and buried oxide/substrate interface, respectively. The device demonstrated a new strategy via electrical characterization with the introduction of substrate-gate coupling that enhanced the formation of hole conduction layer at the channel between drain and source region. Finally, the biosensor shown significant increment in relative changes of drain current level in a linear range of 6.2 to 16.5 % with the increase of positively charge cTnI biomarker concentrations from 1 ng/ml to 10 μg/ml. The device sensitivity of the detection is at 2.51 %·(g/ml)-1 with limit of detection (LOD) down to 3.24 pg/ml.
      5  11
  • Publication
    Fabrication and characterization of ZnO nanostructures for DNA detection
    ( 2013)
    Foo Kai Loong
    Zinc oxide (ZnO), a representative of group II-IV metal-oxide semiconductor material is widely studied in the current research community. ZnO with its wide direct band-gap (3.37eV) and high exciton binding energy (60meV) providing the advantages of their electrical and optical properties. Due to these unique properties and easiness to grow using bottom-up approach combines with high isoelectric point, toxic-free, high surface-area-to-volume ratio, biosafe, and biocompatible, ZnO nanostructures have great interest in the application of biosensor. The aim of this research work is to synthesis, fabricate, and characterize ZnO nanostructures based sensor for DNA immobilization and hybridization detection. Two types of ZnO nanostructures were studied, namely thin films and nanorods (NRs). Highly transparent ZnO thin films were successfully synthesized using ease and low-cost sol-gel spin-coating method. ZnO NRs with nanoscale possessed high crystalline structure was further grown from the asprepared thin films through low-temperature hydrothermal growth. In this thesis, we studied the influence of different solvents on the structure, optical and electrical properties of the ZnO nanostructures. Four types of solvents namely methanol, ethanol, isopropanol, and 2-methoxyethanol had been chosen for ZnO seed solution preparation. The observed results using FESEM indicated that the nanoparticles and nanorods with the size less than 40 nanometer and 60 nanometer, respectively were successfully synthesized. The investigation on optical properties using UV-Vis-NIR spectrophotometer confirmed ZnO is classified as a wide band gap semiconductor material. In order to fabricate a biosensor with high sensitivity and selectivity, a gold nanoparticles (GNPs) were selected for the surface modification of ZnO nanostructures which later formed gold-thiolate conjugation with thiol-modified ssDNA probes. Two approaches were used for the immobilization and hybridization of DNA detection, which were dielectric analysis and electrochemical analysis. DNA detection using dielectric analyzer was done on interdigitated electrodes gold modified ZnO thin films. The developed sensor clearly differentiated complementary and non-complementary of target DNA through the measurement of capacitance, permittivity, and impedance. DNA detection using electrochemical analysis with cyclic voltammetry confirmed surface ZnO NRs modified with (3-Aminopropyl)triethoxysilane (APTES) and gold nanoparticles provided better detection of target DNA in comparison with those only contained gold nanoparticles.
      4  9
  • Publication
    Gold nanoparticles enhanced DNA biosensor based on Silica interdigitated electrodes for detection of Human Papillomavirus
    ( 2018)
    Nor Azizah Parmin
    The increment in cervical cancer cases caused by the genital Human Papillomavirus (HPV) is a major worldwide problem for the women healthcare. In Malaysia, more than 5,000 cervical cancer patients, die from the delay in detecting cancer cells that are spreading to the final stage in 2015. The National Cancer Society of Malaysia (NCSM) reports that more than 11,000 women have been diagnosed with cervical cancer every year, especially young women in the late 30s. Rapid detection methods for the prevention and identification are required to solve the health and safety problems related to this pathogenic virus. Current detection methods require extensive specimen sample preparation and prolonged assay procedures. Thus, this research has focused on developing rapid detection methods, which are capable of sensing these viruses at a higher sensitivity. HPV 16 was used as the standard reference strain for the development of rapid methods. Nanoscaled interdigitated electrodes (IDEs) has been developed for the identification and miniaturizing the size of sensor but have higher performance for the biomedical engineering usage by detecting deoxyribonucleic acid (DNA) of HPV caused cervical cancer. With the conventional lithography (CL) for device fabrication, an electrical biosensor based on gold nanoparticle (GNP) IDE wasconstructed before the addition of 3-aminopropyltriethoxysilane (APTES). The optimized IDE was then employed for the detection of HPV DNA by the introduced two-steps mechanism after the surface modification by APTES. APTES is linking the modified HPV DNA probe with carboxyl group (-COOH) immobilization by covalent binding via amine (-NH2) coupling APTES on the sensing surface based IDE, and DNA hybridization. Surface structure analysis with scanning electron microscopy (SEM) was used to characterize the changes in the surface appearance. Fourier transform infrared (FTIR) spectroscopy analysis was used to assess the attachment procedures. The detection principle works by detecting the changes in the electrical current of IDE, which bridges the source and drain terminal to sense the immobilization of HPV DNA probe and hybridization with target DNA. It was found that the sensor showed the selectivity for HPV DNA target in a linear range with the concentrations ranges from 1 pM to 1 µM. With this analysis, the sensitivity limit of detection (LOD) was approximately 1 pM and it is comparable with the currently available sensors.In addition, the developed biosensor device was able to discriminate among complementary synthetic target, single mismatch, and non-complementary DNA sequences. A commercial, HCII Hybrid capture based Enzyme-Linked Immunosorbent Assay (ELISA) method for 13 types of high-risk HPV including HPV 16 and 18 wasused as a validation technique for confirming the effectiveness of GNP based IDE electrical biosensor in real samples. The advantage of this sensor is fast detection without labeling application and is useful in identifying the strength of HPV DNA probe binding to HPV target. This electrical biosensor system will be useful for the development of devices with on-site analysis.
      7  18
  • Publication
    Impedimetric-based biosensor for Cardiac Troponin 1 detection: sensing strategy aided by Hybrid rGO and Gold Interdigitated Electrode
    ( 2021)
    Steven Taniselass
    Cardiovascular diseases (CVD) are the number one cause of death among the noncommunicable diseases globally. CVD are referred to diseases that associated with the abnormalities of blood flow in heart and often related with ‘heart attack’ condition or in clinical term as an acute myocardial infarction (AMI). Cardiac Troponin I (cTnI) biomarker is widely accepted as gold standard for AMI recognition due to its high specificity. Hence, the need for portable and highly sensitive sensor with fast detection is utmost required to diagnose AMI for fast treatments. Herein, a label-free impedimetric-based cTnI immunosensors were fabricated and their analytical performances were assessed and reported in this thesis. Reduced graphene oxide (rGO) and gold interdigitated electrode (Au-IDE) were employed to develop the immunosensors. The research work is divided into two main sections; first is to obtain a uniform deposition of rGO through single-droplet drop-casting technique and second is to fabricate the cTnI immunosensor aided by rGO. The deposition results revealed the method-3 involving post-sonication technique produces a large and self-assembled of rGO nanoflakes through single-droplet drop-casting without the use of any chemical solvent. Furthermore, the rGO modified Au-IDE devices show an excellent electron mobility, whereby the electrical conductivity was enhanced approximately ~1000-fold compared to the bare devices. Thus, the as-prepared rGO suspension was used to fabricate the immunosensors. Four different surface modification strategies on respective bioelectrodes mediated by the as-prepared rGO suspension were investigated. Electrochemical impedance spectroscopy (EIS) was performed to characterize the immunosensors by sweeping frequencies from 0.1 - 500 kHz at a small AC voltage (25 mV). Results revealed that one of the four immunosensors developed through strategy-4 shows an excellent analytical performance for the cTnI antigen detection in spiked buffer and human serum. A potential surface functionalization mediated by rGO basal plane functional groups was postulated based on XPS and FTIR analyses. The as-fabricated immunosensor showed a wide linear range (10 ag/mL – 100 ng/mL) of cTnI antigen detection in human serum with a linear regression coefficient (R2) of 0.9716 and the lowest analytes detected was 10 ag/mL, whereby it shows highly selective and sensitive trait. The immunosensor also showed a fast-detection that only required 5 minutes for probe and targets binding and stable for nine days. The bioelectrodes were highly reproducible. Hence, such an electrode sensing surface modifications strategy can be further extrapolated for later applications in various biomarker mediated disease diagnoses.
  • Publication
    Synthesis and optimization of Anodic Aluminium Oxide thin film electrode for DNA sensing
    ( 2021)
    Shahidah Arina Shamsuddin
    Recent years, anodic aluminum oxide (AAO) has been extensively explored as an inexpensive, portable and sensitive DNA biosensing device. Apart from their ability to self-grow into well-ordered nanoporous with high porosity and huge surface area, AAO has one special feature wherein their nanopores‘ dimension are capable to be altered and engineered by controlling the main anodizing parameters namely voltage, temperature, time and electrolyte concentration. Since sensitivity and limit of detection of AAO-DNA biosensor depends on the nanopores‘ dimension itself, therefore, many researchers have tried to understand the effect of each anodizing parameters to the nanopores‘ dimension while tried to optimize and improve the sensitivity of AAO in detecting DNA. However, those studies were only focused on the trend of single variable parameter at one time by one-factor-at-a-time method (OFAT), rather than investigating all the interactions between the anodizing parameters simultaneously. Hence, they only reported the improvement made to the sensitivity of their AAO-DNA biosensor at the particular parameter range that they have tested without providing the best of optimum combination levels of all anodizing parameters while the most critical and influential anodizing parameter is still remained unknown. As a contribution to solve these problems, Taguchi method has been proposed in this research as an optimization tool to study the existing interaction between the parameters while at the same time providing the best combination of all parameters levels to improve the AAO-DNA biosensor sensitivity at its optimum performance. Meantime, ANOVA analysis has been proposed to obtain the most influential anodizing parameter to the sensitivity of AAO-DNA biosensor. Prior to optimization, correlation study between the pores‘ dimension and resistance charge transfer (Rct) that affects the sensitivity of AAO-DNA biosensor has been conducted. For this research, AAO thin film-DNA biosensor electrode was synthesized using a single step anodization method in oxalic acid. FESEM was used to observe the AAO surface, while EIS was utilised to study the electrochemical system for DNA hybridization detection. From the first finding, sensitivity of AAO-DNA biosensor was found to be influenced by the ratio of AAO thickness to the pore size. Rct remained under 100 kΩ as long as the ratio of AAO thickness to the pore size was maintained in the range between 1:11 to 1:16. Exceeding the ratio of more than 1:25 will result to the sudden increased in Rct and hence affecting the sensitivity to be reduced. From the second finding, optimization through Taguchi method is the main novelty of this research. The optimum combinations of anodizing parameters were found at 40 V, 17 °C, 0.3 M of oxalic acid at 1 hour. A repetition in experiment was conducted to confirm the efficiency of Taguchi where the sensitivity of the optimized AAO-DNA biosensor electrode was successfully improved to 62.57 % at 0.278 kΩ/M (LOD at 6.497 x 10-15 M) compared to the nominal. From the third finding through ANOVA analysis, the sequences of the most influential anodizing parameter to the AAO-DNA biosensor sensitivity are following the order: anodizing voltage (34.13%) > anodizing time (29.85%) > temperature (20.27%) > electrolyte concentration (15.74%). At the end of this research, optimization of the synthesis of AAO thin film electrode by Taguchi method for DNA sensing was successfully achieved. Since this research had used nonspecific type of DNA target analytes for prototyping development purposed, therefore, it is targeted that this optimized and sensitivity improved AAO thin film electrode will have greater chance to be used widely in the future for detecting various types of DNA, such as dengue, E-coli, or salmonella. Besides, it is of great hope that the outcome from this research may help other researchers to synthesize AAO thin film at its optimum anodizing condition as to improve the sensitivity of the AAO-DNA biosensor
  • Publication
    The optimization of multi-walled carbon nanotubes surface modification via nitric acid oxidation for DNA immobilization
    ( 2014)
    Shahidah Arina Shamsuddin
    This thesis discussed on the optimization of MWCNTs surface modification via nitric acid oxidation for DNA immobilization. After acid oxidation treatment, the impurities in multi-walled carbon nanotube (MWCNTs) such as carbonaceous and metal catalyst particles are successfully reduced as has been analyzed by energy dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD) and thermogravimetric analyzer (TGA). Acid oxidation will caused to the opening of MWCNTs tips and structural defects formed on the MWCNTs surface due to the acid attack. Oxygen containing functional groups, mainly, carboxylic group (COOH) has been introduced on the MWCNTs opened tips and at the defect sites which are useful to interact with other molecules, in this case, aminated-ssDNA probe. The results from fourier transform infrared spectroscopy (FTIR) and Raman Spectroscopy have shown that the COOH amount is depended on the MWCNTs structure defects. Meanwhile, cyclic voltammetry (CV) results have indicated that the immobilization current is directly proportional to the COOH amount. However, structure defect will affect to the immobilization current when ID/IG ratio is increased. The acid oxidation parameter should be optimized, thus the amount of COOH can be increased with the minimal structure defect. Therefore, the main goal to have a maximum immobilization current can be achieved. L9 Taguchi orthogonal array has been used to optimize the acid oxidation parameters. From the result, 5 M of nitric acid concentration, 120 °C of treatment temperature and 6 hours of treatment time are selected as the most optimum combination of acid oxidation parameters. The percentage influence of each main factor is also calculated to be 46% xvi 35% and 18% for nitric acid concentration, treatment time and treatment temperature, respectively. The improvement is happened to be 11.6% of increment in the immobilization current.
      3  19