Theses & Dissertations

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

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Now showing 1 - 5 of 42
  • Publication
    DNA biosensor using gold-nanoparticles interdigitated electrodes for detecting human papillomavirus in cervical cancer
    (Universiti Malaysia Perlis (UniMAP), 2024)
    Nur Fareezah Nadhirah Jaapar
    In Malaysia, about 1,740 new cases of cervical cancer are diagnosed every year and 991 of them die annually because the cancer cells that are spreading unconsciously in the body are not detected in time. Thus, rapid and simple detection methods for prevention and identification are required to solve the morbidity and mortality related to the pathogenic virus. This research has focused on developing a simple, rapid, and novel multi-detection method to detect HPV 16, 18, and 58 at significantly lower concentrations, using these strains as reference to establish effective rapid detection strategies. Firstly, the surface morphology is analyzed using scanning electron microscopy (SEM) and 3D profiler to determine the width and spacing of the finger electrode to 50 μm and 1.5 μm, respectively. Subsequently, the physiochemical properties of colloidal gold Nanoparticles (AuNPs) were investigated using transmission electron microscopy (TEM) (D: ±9.5 nm) and ultraviolet (UV-Vis) (521 nm). Nanoscale IDEs were developed to determine and reduce the sensor size. In addition, IDEs were functionalized with colloidal AuNPs and constructed with APTES as linkers. The optimized IDEs were then used to detect HPV ssDNA by the presented two-step mechanism after surface modification by APTES. APTES links the modified HPV-designed ssDNA probe with the carboxyl group (-COOH) through immobilization by covalent binding via amine (-NH2). Consequently, each HPV ssDNA probe was used to detect its specific ssDNA target during hybridization. The detection principle works by detecting changes in the electrical current of the IDE, bridging the source and drain junction to detect immobilization of the HPV sDNA probe and hybridization with the target sDNA. During the hybridization process, the measured current of the target was higher than its probe as drastic changes in charges generated a spike in the current profile. It was also found that the sensor showed sensitivity for HPV ssDNA target in a linear range with concentrations from 1 aM to 100 μM. The regression coefficient for HPV 16, 18 and 58 was 0.99857, 0.98928 and 0.99583 respectively, and the sensitivity test for HPV 16, 18 and 58 measured at 0.00302 AM-1, 0.074 AM-1 and 0.28089 AM-1 respectively. With this analysis, the limit of detection (LOD) was approximately 0.1 aM, 0.02 aM, and 0.025 aM for HPV 16, 18, and 58 respectively. Next, HPV 18 and 58 were detected in the real sample with an accuracy of 90.42% and 91.92% also validated with PCR significantly. The reusability of the biosensors for HPV 16, HPV 18, and HPV 58 is up to two weeks after their development. Therefore, the first IDEs electrode biosensor based on Au-deposited NPs for early detection of cervical cancer is presented in this research thesis.
  • Publication
    First principles calculations for photovoltaic and optoelectronic properties of pristine and doped-graphene
    (Universiti Malaysia Perlis (UniMAP), 2024)
    Agbolade Lukman Olatomiwa
    This study employed density functional theory (DFT) calculations within the CASTEP code to investigate the effects of boron (B) and beryllium (Be) doping on the structural and optoelectronic properties of graphene. The computational method involved geometry optimization using the (L-BFGS) algorithm, the Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation (GGA) exchange-correlation functional, and ultrasoft pseudopotential. Structural analysis revealed higher bond populations and enhanced structural stability in B-doped configurations compared to Be-doped systems, with B-single-doped configurations showing the highest bond population and shortest average bond length. The electronic properties revealed that increasing B-doping concentrations led to higher band gaps: B-single (0.191 eV), B-dual (0.387 eV) and B-tri (0.44 eV). In contrast, the Be-doped configuration exhibited higher band gaps that decreased with increasing doping: Be-single (0.60 eV), Be-dual (0.550 eV), and Be-tri-doped (0.420 eV), suggesting potential for enhanced carrier mobility. The optical analysis revealed redshifted absorption peaks for B-single-doped graphene, suitable for infrared optoelectronics, while higher B-doping concentrations induced blueshifts, enabling visible and UV applications. The Be-single doped displayed blue shifted peaks, while the Be-dual doped exhibited visible light absorption and the Be-tri-doped had extended absorption peaks in the infrared region, making them suitable for UV applications, and IR image sensors. Additionally, Be-tri-doped graphene exhibited a high potential for photovoltaics, displaying multiple peaks in the visible range (1.6-2.4 eV), thus providing broader absorption properties. These findings provide valuable insight for tailoring the properties of graphene through controlled B and Be doping for diverse optoelectronic applications. The study demonstrates that Be and B doping can induce band gaps in graphene up to 0.60 eV and 0.44 eV, respectively, meeting the requirements for graphene based ON/OFF transistors. Future research can explore modelling graphene-based heterostructures for next-generation optoelectronics, leveraging their high charge mobilities and tuneable band structures.
      2  21
  • Publication
    Label-free gold interdigitated microelectrodes immunosensor for prostate cancer biomarker
    (Universiti Malaysia Perlis (UniMAP), 2020)
    Conlathan Ibau
    Prostate cancer is a slowly proliferating and non-symptomatic form of malignancy in the prostate gland. It is the second most commonly diagnosed type of cancer worldwide, with 28% deaths among diagnosed cases. Although with an introduction of cancer screening in the last few decades had saved countless lives, this technique could not reach out to the patients who live in rural areas due to its inherent complexities and non-portability. Recent developments in label-free and portable biosensing platforms using the gold-standard prostate-specific antigen are catered towards solving this current diagnoses loophole. Similarly, this research work develops a label-free gold interdigitated microelectrodes immunosensor which target to solve these limitations in the current cancer diagnostic technologies. In this work, an interdigitated microelectrodes architecture is chosen due to its superior detection sensitivity, portability and mass manufacturability. The device is fabricated in-house using an established Complementary Metal-Oxide Semiconductor fabrication process, with a gold microelectrode size of 10 μm and interdigitated gap size of 10 μm, integrated with a gold counter electrode and gold pseudo-reference electrode on a silicon dioxide substrate. For biosensing device development, two transducer surface modification schemes are demonstrated. Scheme 1 involves a self-assembled monolayer modification using amino-silanization of 3-aminopropyltriethoxysilane and immobilization of monoclonal antibody specific to prostate-specific antigen on the silicon dioxide substrate, meanwhile Scheme 2 involves modification of self-assembled monolayer using thiolation chemistry of 16-mercaptoundecanoic acid and immobilization of the monoclonal antibody on gold microelectrode surface. Successful sensor’s modification steps are validated using atomic force microscopy, water contact angle measurement, X-ray photoelectron microscopy, and cyclic voltammetry characterization techniques. The binding event of prostate-specific antigen target on device transducer is quantitatively measured using a highly-sensitive Electrochemical Impedance Spectroscopy technique in both Faradaic (in presence of redox species) and non-Faradaic (in absence of redox species) modes of measurement. The Faradaic measurement is performed by measuring the changes in charge transfer resistance in the electrochemical double layer upon target binding, meanwhile in non-Faradaic mode, the detection is made by measuring the changes in the double layer capacitance of the electrochemical system. Using the detection Scheme 1, the bio-detection of prostate-specific antigen in Faradaic mode reveals a linear detection range of 5000 ng/ml to 0.5 ng/ml, with a limit of detection at 0.377 ng/ml. On the other hand, in Scheme 2, Faradaic measurement reveals a linear detection range of 100 ng/ml to 0.01 ng/ml and limit of detection of 0.01 ng/ml. In non-Faradaic mode, linear detection range of 5000 ng/ml to 0.5 ng/ml and limit of detection of 0.5 ng/ml are reported. The sensors’ reproducibility, specificity and stability studies reveal highly promising sensing performances that warrant for future development into a point-of-care biosensing platform.
      2  11
  • Publication
    Nano-aluminosilicate on interdigitated electrode as genosensor for determining epidermal growth factor receptor mutation in non-small cell lung Carcinoma
    (Universiti Malaysia Perlis (UniMAP), 2020)
    Santheraleka Ramanathan
    Lung cancer is caused by mutations of the epidermal growth factor receptor (EGFR), which play an important role in non-small cell lung cancer (NSCLC) diagnosis. The present research demonstrates a specific and sensitive genosensor designed to detect EGFR mutation. Firstly, aluminosilicate was synthesized from joss fly ash. Morphological and structural analyses revealed the size of aluminosilicate to be ~25 nm, affirming the uniformly spherical shaped nanostructure, further revealing its physiochemical properties. Then, the research justified the promising application of aluminosilicate as drug carriers, through enzyme-linked apta-sorbent assay and antimicrobial analysis, claiming that the performance of aluminosilicate conjugated ampicillin is better. Next, the research execution encompasses the fabrication of interdigitated aluminium electrode (AlIDE) with four different microscale gap sizes, 400, 100, 60 and 45 μm. Aluminosilicate synthesized from joss fly ash was deposited on the least variated AlIDE (400 and 100 μm) upon ionic flux and electrolyte scouting performed. Based on the results, optimum microscale gap for aluminosilicate deposition is 100 μm gap sized AlIDE, selected for the development of geneosensor for NSCLC diagnosis. Third execution is the validation of designed oligonucleotides through genomic DNA-based colorimetric assay on unmodified gold nanoparticles (GNPs) for EGFR detection. GNPs aggregation were evidenced by microscopic analyses. The assay resulted a detection limit of 313 nM with mutant target strand. The last research execution is the development of genosensor with nano-aluminosilicate synthesized from joss fly ash was deposited on AlIDE for DNA immobilization and hybridization. Fourier-transform Infrared Spectroscopy analysis was performed at every step of surface functionalization to evident the relevant chemical bonding of biomolecules. Genosensor depicts a sensitive EGFR mutation as it is able to detect apparently at 100 aM mutant against 1 μM DNA probe. An insignificant voltammetry signal generated with wild type strand. With the absence of aluminosilicate, the sensitivity of genosensor is reduced significantly, specifying the important role of aluminosilicate in sensing. Based on the slope of the calibration curve, the attained sensitivity of aluminosilicate modified genosensor was 3.02E-4 A M-1. The detection limit of genosensor computed based on 3σ calculation is 100 aM. Finally, the aims of this research were achieved by developing a rapid and accurate diagnostic device, where the nano-aluminosilicate extracted from joss fly ash significantly enhance the genosensor sensitivity for NSCLC detection.
      9  2
  • Publication
    Gold nanostructures in mediating high-performance medical diagnosis of human blood disease biomarkers
    (Universiti Malaysia Perlis (UniMAP), 2020)
    Iswary Letchumanan
    The current research was carried out using three (3) different human blood disease biomarkers which were C-reactive protein (CRP), blood clotting factor IX (FIX) and squamous cell carcinoma antigen (SCC antigen). Two different types of dual probing system electrode were utilized in this research. A nano gapped electrode with the gap of ~100 nm was designed and modified to capture the target, CRP. Meanwhile, factor IX and SCC antigens were diagnosed by using an interdigitated electrode (IDE), which had finger like structure with the zinc oxide surface. In order to increase the amount of antigen to be captured a gold nanorod (GNR) of a 119 nm in length and 25 nm in width was integrated in CRP detection system. In addition, gold nano-urchins (GNUs) with 60 nm in diameter was integrated into a streptavidin-biotinylated aptamer strategy in Factor IX diagnosis technique. Whereby, dispersed and agglomerated state of gold nanoparticles with 30 nm was used in SCC antigen detection scheme. The physical characterization for the sensing surface and gold nanostructures was properly carried out atomic force microscopy, scanning electron microscopy, 3D nano-profilometry, high-power microscopy and UV–Vis spectroscopy. A comparative analysis in the existence and non-existence of gold nanostructures utilization was performed using electrical characterization. The amperometric measurement by a linear sweep voltage of 0 to 2 V at 0.01 V step voltage was implemented to study the sensitivity and specificity of the blood biomarker interaction. Current research using three different biomarkers which responsible for three different blood disease reveals a lower limit of detection as compared to real concentration of specific biomarkers in human serum. The obtained detection limit as low as pico- to femtomolar range was due to the conjugation of gold nanostructures with antibody (Probe) and the strategy used like streptavidin-biotinylated aptamer for Factor IX detection. Hence, the highlighted novelty of the research is the utilization of different gold nanostructures and also the strategy applied to enhance the detection system. Hence, gold mediated high-performance sensing able to lower the limit of detection down to pico- to femto-molar ranges and hold an outstanding performance in biosensing application.
      4  7