The response of living cells to electric field (EF) has been observed for more than a hundred years, but the mechanism of how cells interact with EF is not entirely ascertained. Although many efforts have been devoted to the application of EF stimulation in tissue engineering and regeneration, the fundamental scientific principle of such practice remains unveiled and keeps drawing attention during the pursuit of consistent outcomes. In this regard, my research focuses on the underlying mechanism by which EF stimulation evokes cellular responses and the EF modulation of cell signaling pathways to physiological behaviors. The first part of my research focuses on developing the platform for controlled EF stimulation and real-time imaging/analysis. High-k dielectric passivated microelectrodes are fabricated to send capacitively coupled alternating current electric field (AC EF) stimulation to cells. I have developed two generations of EF stimulation devices with environmental control chambers: the first one is used to study cell signaling pathway dynamics; the second one is upgraded with long-term culture capability to study cell physiological behaviors. The second part of my research focuses on the quantification and mechanistic study of AC EF perturbation of the extracellular signal-related kinase (ERK) signaling pathway. I demonstrate that AC EF stimulation can induce both inhibition and activation of the ERK pathway, with different AC EF amplitude thresholds and time and magnitude scales. The mechanistic study shows that the ERK activation is initiated by AC EF-induced epidermal growth factor receptor (EGFR) phosphorylation, and the ERK inhibition is related to AC EF-induced change of Ras activities. In addition, these ERK responses show high sensitivity to AC EF waveform and timing, indicating electrostatic coupling mechanism and providing new parameter spaces for further investigation on the modulation of the ERK signaling pathway via AC EF stimulation. The last part of my research steers to cell physiological behaviors under prolonged AC EF stimulation. I report that AC EF stimulation can clearly inhibit cell proliferation and migration, and the inhibition in cell proliferation is sensitive to AC EF amplitude, stimulation pattern, and pulse rising time. These findings can benefit the AC EF application in medical treatment.

Exploration of long-range conductance in non-redox-active proteins at the single molecule scale is aided by the development of innovative, tailor-made quantitative data analysis techniques. This thesis details the rationale behind the proposed approaches, the steps taken to design and implement every method, and the validation of the methodologies using appropriate experiments, benchmarks, and rigorous statistical data analysis. The first chapter conducts a thorough literature review, sets the stage for the subsequent investigation, and underscores the importance of the research questions addressed in this thesis. The second chapter describes the solvent effects on the electronic conductance of a series of Consensus Tetratricopeptide Repeat proteins (CTPR) measured with Scanning Tunneling Microscopy (STM). The study reveals a reversible reduction in electronic conductance when water (H2O) is replaced with heavy water (D2O) due to a ~6-fold decrease in the carrier diffusion constant as proteins become solvated by D2O. Similar observations are made in a ~7 nm long tryptophan zipper protein, while a phenylalanine zipper protein of comparable length remains unchanged in D2O, highlighting the critical role of aromatic residues in proteins lacking redox cofactors. As an extension to this finding, the third chapter describes the development of a machine-learning model to detect the presence of a protein and identify essential features helping in the detection. For this purpose, a solid-state device was engineered to measure the conductance of CTPR-16 protein wires. This approach addresses the limitations in characterizing the STM gap, enables the collection of stable current vs. time data, and provides a statistical understanding of the electronic transport through a protein. The final chapter investigates real-time changes in conductance in response to protein conformation alterations. A deoxyribonucleic acid (DNA) polymerase Φ29 was chosen for its potential utility as a single-molecule DNA sequencing device. The modified enzyme was bound to electrodes functionalized with streptavidin. Φ29 connected by one biotinylated contact and a second nonspecific contact showed rapid small fluctuations in current when activated. Signals were greatly enhanced with two specific contacts. Features in the distributions of conductance increased by a factor of 2 or more over the open-to-closed conformational transition of the polymerase.

My research focuses on studying the interaction between spatiotemporally encoded electric field (EF) and living cells and biomolecules. In this thesis, I report two projects that I have been working on to address these questions. My first project studies the EF modulation of the extracellular-signal-regulated kinase (ERK) pathway. I demonstrated modulation of ERK activities using alternative current (AC) EFs in a new frequency range applied through high-k dielectric passivated microelectrodes with single-cell resolution without electrochemical process induced by the EF stimulation. Further experiments pinpointed a mechanism of phosphorylation site of epidermal growth factor (EGF) receptor to activate the EGFR-ERK pathway that is independent of EGF. AC EFs provide a new strategy to precisely control the dynamics of ERK activation, which may serve as a powerful platform for control of cell behaviors with implications in wide range of biomedical applications. In the second project, I used solid-state nanopore system as the base platform for single molecule experiments, and developed a scalable bottom-up process to construct planar nanopore devices with self-aligned transverse tunneling junctions, all embedded on a nanofluidic chip, based on feedback-controlled reversible electrochemical deposition in a confined nanoscale space. I demonstrated the first simultaneous detection of translocating DNA molecules from both the ionic channel and the tunneling junction with very high yield. Meanwhile, the signal amplitudes from the tunneling junction are unexpectedly high, indicating that these signals are probably dominated by transient currents associated with the fast motion of charged molecules between the transverse electrodes. This new platform provides the flexibility and reproducibility required to study quantum-tunneling-based DNA detection and sequencing. In summary, I have developed two platforms that engineer heterogenous EF at different length scales to modulate live cells and single biomolecules. My results suggest that the charges and dipoles of biomolecules can be electrostatically manipulated to regulate physiological responses and to push detection resolution to single molecule level. Nevertheless, there are still many interesting questions remain, such as the molecular mechanism of EF-protein interaction and tunneling signal extraction. These will be the topics for future investigations.

My research centers on the design and fabrication of biomolecule-sensing devices that combine top-down and bottom-up fabrication processes and leverage the unique advantages of each approach. This allows for the scalable creation of devices with critical dimensions and surface properties that are tailored to target molecules at the nanoscale.

My first project focuses on a new strategy for preparing solid-state nanopore sensors for DNA sequencing. Challenges for existing nanopore approaches include specificity of detection, controllability of translocation, and scalability of fabrication. In a new solid-state pore architecture, top-down fabrication of an initial electrode gap embedded in a sealed nanochannel is followed by feedback-controlled electrochemical deposition of metal to shrink the gap and define the nanopore size. The resulting structure allows for the use of an electric field to control the motion of DNA through the pore and the direct detection of a tunnel current through a DNA molecule.

My second project focuses on top-down fabrication strategies for a fixed nanogap device to explore the electronic conductance of proteins. Here, a metal-insulator-metal junction can be fabricated with top-down fabrication techniques, and the subsequent electrode surfaces can be chemically modified with molecules that bind strongly to a target protein. When proteins bind to molecules on either side of the dielectric gap, a molecular junction is formed with observed conductances on the order of nanosiemens. These devices can be used in applications such as DNA sequencing or to gain insight into fundamental questions such as the mechanism of electron transport in proteins.

In this dissertation I studied the anomalous Hall effect in MgO/Permalloy/Nonmagnetic Metal(NM) based structure, spin polarized current in YIG/Pt based thin films and the origin of the perpendicular magnetic anisotropy(PMA) in the Ru/Co/Ru based structures.

The anomalous Hall effect is the observation of a nonzero voltage difference across a magnetic material transverse to the current that flows through the material and the external magnetic field. Unlike the ordinary Hall effect which is observed in nonmagnetic metals, the anomalous Hall effect is only observed in magnetic materials and is orders of magnitude larger than the ordinary Hall effect. Unlike quantum anomalous Hall effect which only works in low temperature and extremely large magnetic field, anomalous Hall effect can be measured at room temperature under a relatively small magnetic field. This allows the anomalous Hall effect to have great potential applications in spintronics and be a good characterization tool for ferromagnetic materials especially materials that have perpendicular magnetic anisotropy(PMA).

In my research, it is observed that a polarity change of the Hall resistance in the MgO/Permalloy/NM structure can be obtained when certain nonmagnetic metal is used as the capping layer while no polarity change is observed when some other metal is used as the capping layer. This allows us to tune the polarity of the anomalous Hall effect by changing the thickness of a component of the structure. My conclusion is that an intrinsic mechanism from Berry curvature plays an important role in the sign of anomalous Hall resistivity in the MgO/Py/HM structures. Surface and interfacial scattering also make substantial contribution to the measured Hall resistivity.

Spin polarization(P) is one of the key concepts in spintronics and is defined as the difference in the spin up and spin down electron population near the Fermi level of a conductor. It has great applications in the spintronics field such as the creation of spin transfer torques, magnetic tunnel junction(MTJ), spintronic logic devices.

In my research, spin polarization is measured on platinum layers grown on a YIG layer. Platinum is a nonmagnetic metal with strong spin orbit coupling which intrinsically has zero spin polarization. Nontrivial spin polarization measured by ARS is observed in the Pt layer when it is grown on YIG ferromagnetic insulator. This result is contrary to the zero spin polarization in the Pt layer when it is grown directly on SiO2 substrate. Magnetic proximity effect and spin current pumping from YIG into Pt is proposed as the reason of the nontrivial spin polarization induced in Pt. An even higher spin polarization in the Pt layer is observed when an ultrathin NiO layer or Cu layer is inserted between Pt and YIG which blocks the proximity effect. The spin polarization in the NiO inserted sample shows temperature dependence. This demonstrates that the spin current transmission is further enhanced in ultrathin NiO layers through magnon and spin fluctuations.

Perpendicular Magnetic Anisotropy(PMA) has important applications in spintronics and magnetic storage. In the last chapter, I study the origin of PMA in one of the structures that shows PMA: Ru/Co/Ru. By measuring the ARS curve while changing the magnetic field orientation, the origin of the PMA in this structure is determined to be the strain induced by lattice mismatch.

Diamond and cubic boron nitride (c-BN) are ultra wide band gap semiconductors (Eg>3.4 eV) and share similar properties in various aspects, including being isoelectronic, a 1% lattice mismatch, large band gap, high thermal conductivity. Particularly, the negative electron affinity (NEA) of diamond and c-BN is an unusual property that has led to effects such as p-type surface conductivity, low temperature thermionic emission, and photon enhanced thermionic emission. In this dissertation, the interface chemistry and electronic structure of dielectrics on diamond and c-BN are investigated with X-ray and ultraviolet photoemission spectroscopy (XPS and UPS). The first study established that the surface conductive states could be established for thin Al2O3 on diamond using a post deposition H-plasma process. At each step of the atomic layer deposition (ALD) and plasma processing, the band alignment was characterized by in situ photoemission and related to interface charges. An interface layer between the diamond and dielectric layer was proposed to explain the surface conductivity. The second study further investigated the improvement of the hole mobility of surface conductive diamond. A thin layer of Al2O3 was employed as an interfacial layer between surface conductive hydrogen-terminated (H-terminated) diamond and MoO3 to increase the distance between the hole accumulation layer in diamond and negatively charged states in acceptor layer. With an interfacial layer, the ionic scattering, which was considered to limit the hole mobility, was reduced. By combining two oxides (Al2O3 and MoO3), the hole mobility and concentration were modulated by altering the thickness of the Al2O3 interfacial layer. The third study focused on the electronic structure of vanadium-oxide-terminated c-BN surfaces. The vanadium-oxide-termination was formed on c-BN by combining vanadium deposition using molecular beam deposition (MBD) and oxygen plasma treatment. After thermal annealing, a thermally stable NEA was achieved on c-BN. A model was proposed based on the deduced interface charge distribution to explain the establishment of an NEA.

An electrical current with high spin polarization is desirable for the performance of novel spintronics devices, such as magnetic tunnel junction and giant magnetoresistance devices. The generation of spin polarized current can be from ferromagnetic materials or triplet superconductors.

Anomalous Hall effect (AHE) is an effective way to study the properties of magnetic structures. The scattering of electrons by the magnetic moments affects the change of resistance, which can be used to detect the magnetization. In this dissertation, AHE is used to study the perpendicular magnetic anisotropy (PMA) structures, including Co/Pt and Ta/CoFeB/MgO.

Domain walls exist in all ferromagnetic materials. This dissertation studies the domain wall movement in the Ta/CoFeB/MgO structure. A single domain is observed by measuring the anomalous Hall effect. On the other hand, a zero Hall step is successfully observed in a single layer of magnetic material for the first time, which can be used to fabricate advanced domain wall spintronics devices.

Besides the normal ferromagnetic material, the generation of spin polarized current in superconductor is also important for Spintronics. The electrons in superconductors form Cooper pairs. In this dissertation, Andreev Reflection Spectroscopy (ARS) is used to study the spin configuration in Cooper pairs.

Generally, ferromagnetism and superconductivity can not co-exist. In this dissertation, the Bi/Ni bilayer structure has been studied with ARS, and the measurement results show a triplet superconductivity below 4K. The appearance of superconductivity is believed to be attributed to the Bi-Ni interface, and the triplet Cooper pair makes it a promising candidate in superconducting spintronics.

Besides, a Bi3Ni single crystal is also studied with ARS. The measurements show a singlet superconductivity in this material, which further proves the importance of the Bi/Ni interface to achieve triplet superconductivity.

Finally, ARS is also used to study NbSe2 monolayer, a 2D superconductor. The monolayer is verified by the measurements of critical temperature and critical field, which are different from the values of multilayer or bulk. Andreev reflection results show that NbSe2 monolayer is a singlet superconductor and there is no node exist in the superconducting gap for a in plane magnetic field up to 58 kOe.

My research has been focusing on the innovations of material and structure designs, and the development of fabrication processes of novel nanoelectronics devices.

My first project addresses the long-existing challenge of implantable neural probes, where high rigidity and high flexibility for the probe need to be satisfied at the same time. Two types of probes that can be used out of the box have been demonstrated, including (1) a compact probe that spontaneously forms three-dimensional bend-up devices only after implantation, and (2) an ultra-flexible probe as thin as 2 µm attached to a small silicon shaft that can be accurately delivered into the tissue and then get fully released in situ without altering its shape and position as the support is fully retracted. This work provides a general strategy to prepare ultra-small and flexible implantable probes that allow high insertion accuracy and minimal surgical damages with best biocompatibility.

My second project focuses on the injection and characterization of carrier spins in single crystal diamond based nanoscale devices. The conventional diamond-based quantum information process that exploits nitrogen vacancy centers faces a major barrier of large scale communication. Electron/hole spin in diamond devices, on the other hand, could also be a good candidate for quantum computing due to the very small spin-orbit coupling and great coherent transport length of spin. To date, there has been no demonstration of carrier spin transport in diamond. In this work, I try to answer this fundamental question of how to inject and characterize electron spins in Boron doped diamond. Nanoscale diamond devices have been fabricated to investigate this question, including Hall bar device for material characterization, and lateral spin valve for injecting spin-polarized current into a mesoscopic diamond bar and detecting induced pure spin current. The preliminary results show signatures of spin transport in heavily doped diamond films.

Looking into the future, the knowledge we obtained in these two projects, including the strategy to integrate thin-film nanoelectronics devices on a flexible bio-probe configuration, and how to build spintronic devices with diamond structures, could be unified in the exploration of spin-based sensors in biological systems.

Driven by the curiosity for the secret of life, the effort on sequencing of DNAs and other large biopolymers has never been respited. Advanced from recent sequencing techniques, nanotube and nanopore based sequencing has been attracting much attention. This thesis focuses on the study of first and crucial compartment of the third generation sequencing technique, the capture and translocation of biopolymers, and discuss the advantages and obstacles of two different nanofluidic pathways, nanotubes and nanopores for single molecule capturing and translocation. Carbon nanotubes with its constrained structure, the frictionless inner wall and strong electroosmotic flow, are promising materials for linearly threading DNA and other biopolymers for sequencing. Solid state nanopore on the other hand, is a robust chemical, thermal and mechanical stable nanofluidic device, which has a high capturing rate and, to some extent, good controllable threading ability for DNA and other biomolecules. These two different but similar nanofluidic pathways both provide a good preparation of analyte molecules for the sequencing purpose. In addition, more and more research interests have move onto peptide chains and protein sensing. For proteome is better and more direct indicators for human health, peptide chains and protein sensing have a much wider range of applications on bio-medicine, disease early diagnoses, and etc. A universal peptide chain nanopore sensing technique with universal chemical modification of peptides is discussed in this thesis as well, which unifies the nanopore capturing process for vast varieties of peptides. Obstacles of these nanofluidic pathways are also discussed. In the end of this thesis, a proposal of integration of solid state nanopore and fixed-gap recognition tunneling sequencing technique for a more accurate DNA and peptide readout is discussed, together with some early study work, which gives a new direction for nanopore based sequencing.

Single molecule identification is one essential application area of nanotechnology. The application areas including DNA sequencing, peptide sequencing, early disease detection and other industrial applications such as quantitative and quantitative analysis of impurities, etc. The recognition tunneling technique we have developed shows that after functionalization of the probe and substrate of a conventional Scanning Tunneling Microscope with recognition molecules ("tethered molecule-pair" configuration), analyte molecules trapped in the gap that is formed by probe and substrate will bond with the reagent molecules. The stochastic bond formation/breakage fluctuations give insight into the nature of the intermolecular bonding at a single molecule-pair level. The distinct time domain and frequency domain features of tunneling signals were extracted from raw signals of analytes such as amino acids and their enantiomers. The Support Vector Machine (a machine-learning method) was used to do classification and predication based on the signal features generated by analytes, giving over 90% accuracy of separation of up to seven analytes. This opens up a new interface between chemistry and electronics with immediate implications for rapid Peptide/DNA sequencing and molecule identification at single molecule level.