Recent drastic improvement of plasma stability and confinement in the high performance C-2 advanced beam-driven field-reversed configuration (FRC) experiment at Tri Alpha Energy, Inc. (TAE) has led to consistently reproducible stable plasmas suitable for transport study. To understand and support the ongoing efforts towards an FRC-based reactor, the sources of the fluctuations and the mechanisms of the transport must first be identified such that a suitable transport scaling may be found and applied toward predicting confinement performance in larger, hotter, and denser FRC plasmas.

In the first half of this thesis, a mature, well-benchmarked turbulence simulation code, the Gyrokinetic Toroidal Code (GTC), has been extended and applied to a system with experimentally realistic C-2 parameters. Using GTC, local electrostatic drift-wave stabilities in the core and scrape-off layer (SOL) regions of C-2 have been characterized and compared to experimental findings. The drift-wave is found to be stable in the core. On the other hand, in the SOL, a class of ion-to-electron scale instabilities is observed. These simulation results are consistent with density fluctuation measurements in C-2.

Since experimental measurements show that fluctuations exist in the core, the discovery of the robust stability of the core suggests that the fluctuations may originate from the SOL. In the second half of this thesis, a new turbulence simulation code, A New Code (ANC), has been developed to study nonlocal phenomenon. Using ANC, the linear propagation and nonlinear spreading of a single-mode instability from the SOL to the core has been characterized. It is shown that nonlocal effects, due to the ion finite Larmor radius (FLR) effect and ion polarization drift, allows for the coupling of different drift-surfaces and for the instability in the SOL to spread into the core. The phase velocities of the instability is consistent with experimental measurements of radial propagation. The nonlinear saturation of the instability shows that the saturated mode amplitude in the SOL is higher than in the core, again, consistent with experimental measurements.

In addition, the first turbulent transport simulation in the FRC SOL has also been performed using gyrokinetic ions and adiabatic electrons. Self-consistent ion heat flux is calculated from these simulations to be ~6[kW/m^2] while an upper bound for the electron heat flux is calculated to be ~4[MW/m^2] through electron test particles, though the self-consistent electron heat flux is expected to be lower. An inverse spectral cascade is also observed, with unstable shorter wavelength modes feeding into stable or damped long wavelength modes.

Monoclonal antibodies are being increasingly utilized as highly-specific sensing elements and linkers for biosensing and chemical detection applications. Ideally, such sensors would demonstrate a real-time response to analyte concentration, but devices incorporating antibodies are often limited by the kinetics of antibody-antigen binding, which can take tens of minutes to measure accurately. Fast, single-molecule techniques show potential for reducing measurement time and revealing kinetics that are otherwise hidden during ensemble measurements. In this work, field effect transistors (FET) based on carbon nanotubes were used to record the binding activity of antibody 3C6 molecules with paclitaxel at the microsecond timescale. Single-molecule measurements revealed individual antibody-antigen binding and unbinding events, with statistics correlated to paclitaxel concentration, while ensemble measurements exhibited no consistent dependence on paclitaxel concentration. Further analysis of the single-molecule binding statistics showed deviations from simple receptor-ligand binding, suggesting the presence of cooperative binding dynamics between the individual binding sites on the 3C6 molecule. The measurement accuracy of the binding dynamics was limited by bandwidth, suggesting that measurements performed at higher bandwidth could increase the accuracy of the binding kinetics values obtained. Equilibration times for the single-molecule carbon nanotube FETs were under 60 seconds, demonstrating rapid response times that can be used in real-time sensing applications.

Studies of single biomolecules provide information that is buried in an ensemble-based measurement, including the evolution of an individual biomolecule’s behavior over time. Recent work showed that an electronic sensor composed of single-walled carbon nanotube field-effect transistors (SWCNT-FETs) can observe an individual biomolecule’s conformational motions over time and obtain accurate measurements of catalytic rates for a variety of enzymes (1-3).

This dissertation expands the scope of transistor-based biosensing techniques through several strategies. The first strategy extends previous work by investigating similar enzymes, such as other DNA polymerases, in order to identify unique characteristics of each enzyme. A second strategy focuses on investigating the dynamics of biomolecular interactions that have not been previously studied by this technique, such as ligand-binding interactions. A third strategy makes refinements to the measurement or analysis techniques to uncover additional, subtler dynamics and other information that was previously hidden in the acquired signal.

The dissertation is organized into two main parts. The first part (Chapters 1-3) discusses new measurements performed using the SWCNT-FET technique. Chapter 1 provides a brief introduction to the SWCNT-FET biosensing technique and details the methods and materials used in the experiments described in the following two chapters.

Chapter 2 studies the behavior of a weakly-interacting antibody-antigen system: antibody 3C6 in the presence of the antigen paclitaxel. SWCNT-FET recordings of antigen-antibody binding exhibited two conductance states corresponding to bound and unbound configurations, like the two-level dynamics previously recorded from enzymatic catalysis. The SWCNT-FET signal correlated with antigen concentration, remaining relatively static at concentrations far from the value of the dissociation constant K_D and fluctuating most actively near K_D. Analysis of the distribution of single-molecule bound and unbound times determined a value of K_D = 30 nM, a binding rate k_off = 10^4 s^-1, and a Hill coefficient of binding cooperativity of 1.8. Chapter 2 also compares antibody-antigen dynamics recorded in single-molecule, few-molecule, and many-molecule regimes of biofunctionalization.

Chapter 3 extends previous work on DNA polymerases by investigating an alternate polymerase, φ29 DNA polymerase, and characterizes its conformational motions and catalytic efficiency. Chapter 3 finds that the catalytic efficiency of φ29 DNA polymerase depends on the template composition. The enzyme continuously processed heteropolymer ssDNA templates and homopolymer templates containing thymine and cytosine at rates of ~50 s^-1 for 3-5 mins, but exhibited only 1-2 s bursts of conformational motion among 60 s of pauses when processing homopolymer templates containing adenine and guanine. Single-molecule recordings of the latter two templates showed the ability of the SWCNT-FET to measure enzyme motion when the enzyme’s activity in time was less than 2%, in contrast with ensemble-based observations which did not detect catalysis at such low activity. In addition, detailed analyses of the open and closed conformations of φ29 DNA polymerase suggested the presence of multiple operating modes during the catalytic cycle, including a closed conformation whose duration was 8 times longer than the typical catalytic event.

The second part of the dissertation (Chapters 4-5) expands the analysis toolkit with new methods. Chapter 4 introduces a wavelet-based denoising scheme and describes the optimization and application of the scheme to SWCNT-FET sensor signals. This chapter demonstrates the effectiveness of wavelet denoising in removing both low- and high-frequency noise from the SWCNT-FET sensor output and describes the artifacts introduced by the denoising process. The wavelet denoising scheme is also compared to other digital denoising methods.

Finally, Chapter 5 describes an automated analysis procedure for identifying conformational events and characterizing each event using a set of features. SWCNT-FET measurements from two variants of Taq DNA polymerase are compared to highlight features that are correlated to enzyme behavior, correlated to experimental noise, or completely uncorrelated. In addition, a preliminary analysis using principal component analysis (PCA) serves as an example of machine learning techniques that could be used in the future.