College of Engineering

This thesis is submitted in partial fulfillment of the requirements for obtaining the degree of Master of Science in Electrical Engineering. I further declare that no potential conflict of interest exists with respect to the research, data collection, authorship, presentation and/or publication of this thesis. The main goal of this thesis is to selectively and rapidly detect the SARS-CoV-2 spike protein antigen in situ.

The designed sensor successfully detects the SARS-CoV-2 spike protein and exhibits outstanding electrical behavior for detection. The electronic transport properties of the rGO-FET biosensor such as transmission spectrum, electronic current and transfer curves are studied by using semiempirical modeling combined with a non-equilibrium Green's function. The rGO FET-based biosensor is developed and tested to take advantage of the unique electronic properties of the rGO channel and offer a fast, rapid, easy and accurate detection method for SARS-CoV-2 virus.

Introduction

• Overview
• Statement of the Problem
• Research Objectives
• Thesis Organization

Chapter 2 discusses and presents the literature related to this study, as follows, the COVID-19 pandemic, virus structure, SARS-CoV-2 detection techniques, virus detection biosensors, SARS-CoV-2 detection biosensors, graphene, band gap engineering in graphene and finally rGO functions and applications.

Literature Review

• COVID-19 Pandemic
• Virus Structure
• Coronavirus Detection Techniques
• Biosensors for Viral Detection
• Biosensors for SARS-CoV-2 Detection
• Graphene
• Bandgap Engineering in Graphene
• RGO Features and Applications

Angiotensin converting enzyme 2 (ACE2) which is surface structure found on most of the human cells. Different symptoms such as fever, cough, shortness of breath and fatigue have been detected in SARS-CoV-2 patients, but these symptoms are not compelling and are very similar to the number of other viral infections, therefore accurate diagnosis techniques are very necessary. Artificial intelligence has been used in various occasions, such as the prediction of virus spread, contact tracing, SARS-CoV-2 case monitoring and early diagnosis to help the medical staff [23].

Transcription Loop-Mediated Isothermal Amplification” RT-LAMP was introduced by Zhu's team [27], the newly emerging technique showed superior specificity compared to RT-PCR (the specificity of the test and the analytical sensitivity of SARS-CoV-2 are 100%), a collection of primer sets, opening reading frame and SARS-CoV-2N genes. Clustered Regular Interspaced Short Palindromic Repeats (CRISPR-Cas), a pending clinical validation technique previously used to detect bacteria, microRNAs and cancer mutations, has been trialled for the diagnosis of SARS-CoV-2. The binding event of the virus causes an increase in impedance that is proportional to the virus concentration [40].

Basically, three key factors should not be tolerated in SARS-CoV-2 detection, namely identification targets, detection methods and measured signals. Viral infection can be detected by detecting one of the following: whole virus, viral RNA/DNA, and antibody/antigen [9]. They used FETs using 2D semiconductor materials to detect SARS-CoV-2, depending on the easily modified electronic nature of such materials and their sensitivity.

The group used transition metal dichalcogenide (TMDC) semiconducting WSe2 monolayers functionalized with SARS-CoV-2 as a detection platform and achieved an LOD of 25 fg/μL in 0.01X phosphate-buffered saline (PBS) [49] . Again, AuNPs were used in this research with the SARS-CoV-2 spike protein antigen (SARS-CoV-2 Ag) being the detection target. The applicability of another interesting nanomaterial called Quantum Dots (QDs) was evaluated for the diagnosis of SARS-CoV-2.

Quantum Dots (QDs) which are nanometer-sized semiconductor particles with attractive properties [53] are very promising candidates yet to be used in the diagnosis and detection of SARS-CoV-2 field according to Sultan et al. 's review [54] .

Figure 1: SARS-CoV-2 structure [12]

Semi-Empirical Modelling and Simulation Settings

• Introduction
• FET Design
• Electrodes
• Channel
• Gate
• Metal Nanoparticles
• Viruses
• COVID-19 Spike Protein
• Device Testing
• Electrode-Channel Interface
• Semi-Empirical Model

The size compatibility of the electrodes was further confirmed from the convergence of the software simulations, moreover the chosen dimensions showed the optimal behavior. Dirichlet condition along the C direction and Neumann boundary condition along the A and B directions were applied to the electrodes when studying the device performance. This conclusion was further investigated by Quantumwise ATK software and the results are discussed in the coming sections.

Oxygen functional groups are randomly spread on the surface of rGO, in fact this is one of the challenges when dealing with graphene, each sample has its unique structure, therefore it is difficult to produce identical samples with exactly the same electronic behavior [102] . Studies have found four types of oxygen-containing groups in graphene, namely hydroxyl (C-OH), epoxide (C-O-C), carboxyl (COOH) and carbonyl (C˭˭O), with the former two located in the basal plane and responsible for most of the unique electronic properties of graphene, while the latter was found at the edges [103–107]. Second, another reason to use MNPs is to avoid the immediate interaction between the rGO channel and the biomolecules, this is so important since the immobilization of the antibodies can affect the electronic structure of the rGO, such as conductance and electron distribution [112] .

Bio-recognition molecules are used to further increase the selectivity of the sensor and amplify its affinity. According to the literature the gate electrode can be placed either on top, back or on top and back (double structure) of the channel. The top-gate structure is useful for high-frequency applications as it provides precise control of the graphene channel, on the other hand, the back-gate setup is more suitable for bio-sensing and photodetection applications because it allows the graphene channel to be in full contact. with the detection medium.

The port for the designed sensor is placed on the back of the channel, but does not touch it. The sensor is not expected to show a significant change in the transmission spectrum when exposed to the other virus, as the detection probes used are SARS-CoV-2 antibodies. Nevertheless, Kohn-Sham equations and single-particle states can pose many problems in terms of insufficient description of the unoccupied energy levels and the need for parallel computers to perform the demanding calculations.

Another interesting value known as the self-energy, which is a description of the effect the electrode states have on the electronic structure of the central region, is calculated by the software, basically four methods are available, namely direct self-energy [129], self-recursion energy [129] 130], Krylov- self-energy [131–132] and finally sparse recursion self-energy, which is used in our design due to its effectiveness with large-sized systems [130] .

Figure 7: Electrodes dimensions and geometry 3.2.2 Channel

Results and Discussions

Channel’s Performance

FET-Based Biosensor Performance

• Biosensor’s Characterization
• Biosensor’s Transmission Spectrum
• Biosensor’s Output Curves
• Biosensor’s Selectivity

At first glance, it can be seen that all spectra have a similar behavior in general, which is a suppressed valence band, a multiple. We previously expected that the transmission spectrum of the whole system would be significantly reduced in its valence band until complete damping is achieved in some positions. This behavior can be attributed mainly to two main reasons: firstly, the position of the functional oxygen groups near the edge, which increases the backscattering and localization of the states [141], and secondly, the addition of gold electrodes or metal contacts (MC) which introduces an additional contact resistance, which has resulting in reduced conductivity.

Contact resistance is actually one of the biggest challenges when designing a device based on a 2D material since a large part of the applied bias is lost to parasitic resistance [108]. Second, the metallization can also be observed by the unmistakably reduced transmission compared to that of the channel before the MCs are added (from 16 to almost 9). The appearance of Lorentzians and reduced conductivity has been specifically attributed to the impact of destructive interference on electrons traveling along the FET, which is a result of the continuously expanding nature of MCs [152].

In contrast, the virus-bound sensor shows a distinct negative differential resistance (NDR) behavior, this result was expected because MNP channel decoration was used here to avoid direct contact between the biotarget and the rGO channel, as this may lead to of changing the electronic structure of rGO, which eventually results in a distorted. In Serhan's work, the NDR phenomenon was also related to the coverage ratio, which is the percentage of carbon atoms that have bonds with oxygen functional groups in the sample. It is worth noting that our rGO channel has 11.2% coverage, which is very close to the ratios in the mentioned survey.

These opposing trends were attributed to the charge carriers' movement between the introduced MNPs and the rGO sheet. It can be noted that the movement of the device channel was toward the MNPs in the Cu atoms case while it was in the opposite direction in the Ag atoms situation. The COVID-19 dot antibody was used to ensure the sensor accuracy and selectivity for the COVID-19 dot antigen.

It is expected that the target molecules of the COVID-19 spike antigen will bind to the COVID-19 spike.

Figure 17: I-V curve of the bare G-FET sensor at V g = 1 v

Conclusion and Future Works

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Lee, “pH sensing characteristics and biosensing application of solution-controlled reduced graphene oxide field-effect transistors,” Biosens. Szunerits, “Reduced graphene oxide-based field-effect transistors for the detection of human papillomavirus E7 protein in saliva,” Anal. Zhang, “A field-effect transistor modified with reduced graphene oxide for immunodetection of Ebola virus,” Microchim.

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