Matching Items (65)
- Genre: Doctoral Dissertation
- Creators: Goryll, Michael
Detection of molecular interactions is critical for understanding many biological processes, for detecting disease biomarkers, and for screening drug candidates. Fluorescence-based approach can be problematic, especially when applied to the detection of small molecules. Various label-free techniques, such as surface plasmon resonance technique are sensitive to mass, making it extremely challenging to detect small molecules. In this thesis, novel detection methods for molecular interactions are described.
First, a simple detection paradigm based on reflectance interferometry is developed. This method is simple, low cost and can be easily applied for protein array detection.
Second, a label-free charge sensitive optical detection (CSOD) technique is developed for detecting of both large and small molecules. The technique is based on that most molecules relevant to biomedical research and applications are charged or partially charged. An optical fiber is dipped into the well of a microplate. It detects the surface charge of the fiber, which does not decrease with the size (mass) of the molecule, making it particularly attractive for studying small molecules.
Third, a method for mechanically amplification detection of molecular interactions (MADMI) is developed. It provides quantitative analysis of small molecules interaction with membrane proteins in intact cells. The interactions are monitored by detecting a mechanical deformation in the membrane induced by the molecular interactions. With this novel method small molecules and membrane proteins interaction in the intact cells can be detected. This new paradigm provides mechanical amplification of small interaction signals, allowing us to measure the binding kinetics of both large and small molecules with membrane proteins, and to analyze heterogeneous nature of the binding kinetics between different cells, and different regions of a single cell.
Last, by tracking the cell membrane edge deformation, binding caused downstream event – granule secretory has been measured. This method focuses on the plasma membrane change when granules fuse with the cell. The fusion of granules increases the plasma membrane area and thus the cell edge expands. The expansion is localized at the vesicle release location. Granule size was calculated based on measured edge expansion. The membrane deformation due to the granule release is real-time monitored by this method.
In mesoscopic physics, conductance fluctuations are a quantum interference phenomenon that comes from the phase interference of electron wave functions scattered by the impurity disorder. During the past few decades, conductance fluctuations have been studied in various materials including metals, semiconductors and graphene. Since the patterns of conductance fluctuations is related to the distributions and configurations of the impurity scatterers, each sample has its unique pattern of fluctuations, which is considered as a sample fingerprint. Thus, research on conductance fluctuations attracts attention worldwide for its importance in both fundamental physics and potential technical applications. Since early experimental measurements of conductance fluctuations showed that the amplitudes of the fluctuations are on order of a universal value (e2/h), theorists proposed the hypothesis of ergodicity, e.g. the amplitudes of the conductance fluctuations by varying impurity configurations is the same as that from varying the Fermi energy or varying the magnetic field. They also proposed the principle of universality; e.g., that the observed fluctuations would appear the same in all materials. Recently, transport experiments in graphene reveal a deviation of fluctuation amplitudes from those expected from ergodicity.
Thus, in my thesis work, I have carried out numerical research on the conductance fluctuations in GaAs nanowires and graphene nanoribbons in order to examine whether or not the theoretical principles of universality and ergodicity hold. Finite difference methods are employed to study the conductance fluctuations in GaAs nanowires, but an atomic basis tight-binding model is used in calculations of graphene nanoribbons. Both short-range disorder and long-range disorder are considered in the simulations of graphene. A stabilized recursive scattering matrix technique is used to calculate the conductance. In particular, the dependence of the observed fluctuations on the amplitude of the disorder has been investigated. Finally, the root-mean-square values of the amplitude of conductance fluctuations are calculated as a basis with which to draw the appropriate conclusions. The results for Fermi energy sweeps and magnetic field sweeps are compared and effects of magnetic fields on the conductance fluctuations of Fermi energy sweeps are discussed for both GaAs nanowires and graphene nanoribbons.
Zinc oxide (ZnO), a naturally n-type semiconductor has been identified as a promising candidate to replace indium tin oxide (ITO) as the transparent electrode in solar cells, because of its wide bandgap (3.37 eV), abundant source materials and suitable refractive index (2.0 at 600 nm). Spray deposition is a convenient and low cost technique for large area and uniform deposition of semiconductor thin films. In particular, it provides an easier way to dope the film by simply adding the dopant precursor into the starting solution. In order to reduce the resistivity of undoped ZnO, many works have been done by doping in the ZnO with either group IIIA elements or VIIA elements using spray pyrolysis. However, the resistivity is still too high to meet TCO's resistivity requirement. In the present work, a novel co-spray deposition technique is developed to bypass a fundamental limitation in the conventional spray deposition technique, i.e. the deposition of metal oxides from incompatible precursors in the starting solution. With this technique, ZnO films codoped with one cationic dopant, Al, Cr, or Fe, and an anionic dopant, F, have been successfully synthesized, in which F is incompatible with all these three cationic dopants. Two starting solutions were prepared and co-sprayed through two separate spray heads. One solution contained only the F precursor, NH 4F. The second solution contained the Zn and one cationic dopant precursors, Zn(O 2CCH 3) 2 and AlCl 3, CrCl 3, or FeCl 3. The deposition was carried out at 500 °C; on soda-lime glass in air. Compared to singly-doped ZnO thin films, codoped ZnO samples showed better electrical properties. Besides, a minimum sheet resistance, 55.4 Ω/sq, was obtained for Al and F codoped ZnO films after vacuum annealing at 400 °C;, which was lower than singly-doped ZnO with either Al or F. The transmittance for the Al and F codoped ZnO samples was above 90% in the visible range. This co-spray deposition technique provides a simple and cost-effective way to synthesize metal oxides from incompatible precursors with improved properties.
Resistance switching in chalcogenide based programmable metallization cells (PMC) and sensors under gamma-rays
Chalcogenide glass (ChG) materials have gained wide attention because of their applications in conductive bridge random access memory (CBRAM), phase change memories (PC-RAM), optical rewritable disks (CD-RW and DVD-RW), microelectromechanical systems (MEMS), microfluidics, and optical communications. One of the significant properties of ChG materials is the change in the resistivity of the material when a metal such as Ag or Cu is added to it by diffusion. This study demonstrates the potential radiation-sensing capabilities of two metal/chalcogenide glass device configurations. Lateral and vertical device configurations sense the radiation-induced migration of Ag+ ions in germanium selenide glasses via changes in electrical resistance between electrodes on the ChG. Before irradiation, these devices exhibit a high-resistance `OFF-state' (in the order of 10E12) but following irradiation, with either 60-Co gamma-rays or UV light, their resistance drops to a low-resistance `ON-state' (around 10E3). Lateral devices have exhibited cyclical recovery with room temperature annealing of the Ag doped ChG, which suggests potential uses in reusable radiation sensor applications. The feasibility of producing inexpensive flexible radiation sensors has been demonstrated by studying the effects of mechanical strain and temperature stress on sensors formed on flexible polymer substrate. The mechanisms of radiation-induced Ag/Ag+ transport and reactions in ChG have been modeled using a finite element device simulator, ATLAS. The essential reactions captured by the simulator are radiation-induced carrier generation, combined with reduction/oxidation for Ag species in the chalcogenide film. Metal-doped ChGs are solid electrolytes that have both ionic and electronic conductivity. The ChG based Programmable Metallization Cell (PMC) is a technology platform that offers electric field dependent resistance switching mechanisms by formation and dissolution of nano sized conductive filaments in a ChG solid electrolyte between oxidizable and inert electrodes. This study identifies silver anode agglomeration in PMC devices following large radiation dose exposure and considers device failure mechanisms via electrical and material characterization. The results demonstrate that by changing device structural parameters, silver agglomeration in PMC devices can be suppressed and reliable resistance switching may be maintained for extremely high doses ranging from 4 Mrad(GeSe) to more than 10 Mrad (ChG).
The high cut-off frequency of deep sub-micron CMOS technologies has enabled the integration of radio frequency (RF) transceivers with digital circuits. However, the challenging point is the integration of RF power amplifiers, mainly due to the low breakdown voltage of CMOS transistors. Silicon-on-insulator (SOI) metal semiconductor field effect transistors (MESFETs) have been introduced to remedy the limited headroom concern in CMOS technologies. The MESFETs presented in this thesis have been fabricated on different SOI-CMOS processes without making any change to the standard fabrication steps and offer 2-30 times higher breakdown voltage than the MOSFETs on the same process. This thesis explains the design steps of high efficiency and wideband RF transmitters using the proposed SOI-CMOS compatible MESFETs. This task involves DC and RF characterization of MESFET devices, along with providing a compact Spice model for simulation purposes. This thesis presents the design of several SOI-MESFET RF power amplifiers operating at 433, 900 and 1800 MHz with ~40% bandwidth. Measurement results show a peak power added efficiency (PAE) of 55% and a peak output power of 22.5 dBm. The RF-PAs were designed to operate in Class-AB mode to minimize the linearity degradation. Class-AB power amplifiers lead to poor power added efficiency, especially when fed with signals with high peak to average power ratio (PAPR) such as wideband code division multiple access (W-CDMA). Polar transmitters have been introduced to improve the efficiency of RF-PAs at backed-off powers. A MESFET based envelope tracking (ET) polar transmitter was designed and measured. A low drop-out voltage regulator (LDO) was used as the supply modulator of this polar transmitter. MESFETs are depletion mode devices; therefore, they can be configured in a source follower configuration to have better stability and higher bandwidth that MOSFET based LDOs. Measurement results show 350 MHz bandwidth while driving a 10 pF capacitive load. A novel polar transmitter is introduced in this thesis to alleviate some of the limitations associated with polar transmitters. The proposed architecture uses the backgate terminal of a partially depleted transistor on SOI process, which relaxes the bandwidth and efficiency requirements of the envelope amplifier in a polar transmitter. The measurement results of the proposed transmitter demonstrate more than three times PAE improvement at 6-dB backed-off output power, compared to the traditional RF transmitters.
Continuous monitoring in the adequate temporal and spatial scale is necessary for a better understanding of environmental variations. But field deployments of molecular biological analysis platforms in that scale are currently hindered because of issues with power, throughput and automation. Currently, such analysis is performed by the collection of large sample volumes from over a wide area and transporting them to laboratory testing facilities, which fail to provide any real-time information. This dissertation evaluates the systems currently utilized for in-situ field analyses and the issues hampering the successful deployment of such bioanalytial instruments for environmental applications. The design and development of high throughput, low power, and autonomous Polymerase Chain Reaction (PCR) instruments, amenable for portable field operations capable of providing quantitative results is presented here as part of this dissertation. A number of novel innovations have been reported here as part of this work in microfluidic design, PCR thermocycler design, optical design and systems integration. Emulsion microfluidics in conjunction with fluorinated oils and Teflon tubing have been used for the fluidic module that reduces cross-contamination eliminating the need for disposable components or constant cleaning. A cylindrical heater has been designed with the tubing wrapped around fixed temperature zones enabling continuous operation. Fluorescence excitation and detection have been achieved by using a light emitting diode (LED) as the excitation source and a photomultiplier tube (PMT) as the detector. Real-time quantitative PCR results were obtained by using multi-channel fluorescence excitation and detection using LED, optical fibers and a 64-channel multi-anode PMT for measuring continuous real-time fluorescence. The instrument was evaluated by comparing the results obtained with those obtained from a commercial instrument and found to be comparable. To further improve the design and enhance its field portability, this dissertation also presents a framework for the instrumentation necessary for a portable digital PCR platform to achieve higher throughputs with lower power. Both systems were designed such that it can easily couple with any upstream platform capable of providing nucleic acid for analysis using standard fluidic connections. Consequently, these instruments can be used not only in environmental applications, but portable diagnostics applications as well.
Super-Resolution (SR) techniques are widely developed to increase image resolution by fusing several Low-Resolution (LR) images of the same scene to overcome sensor hardware limitations and reduce media impairments in a cost-effective manner. When choosing a solution for the SR problem, there is always a trade-off between computational efficiency and High-Resolution (HR) image quality. Existing SR approaches suffer from extremely high computational requirements due to the high number of unknowns to be estimated in the solution of the SR inverse problem. This thesis proposes efficient iterative SR techniques based on Visual Attention (VA) and perceptual modeling of the human visual system. In the first part of this thesis, an efficient ATtentive-SELective Perceptual-based (AT-SELP) SR framework is presented, where only a subset of perceptually significant active pixels is selected for processing by the SR algorithm based on a local contrast sensitivity threshold model and a proposed low complexity saliency detector. The proposed saliency detector utilizes a probability of detection rule inspired by concepts of luminance masking and visual attention. The second part of this thesis further enhances on the efficiency of selective SR approaches by presenting an ATtentive (AT) SR framework that is completely driven by VA region detectors. Additionally, different VA techniques that combine several low-level features, such as center-surround differences in intensity and orientation, patch luminance and contrast, bandpass outputs of patch luminance and contrast, and difference of Gaussians of luminance intensity are integrated and analyzed to illustrate the effectiveness of the proposed selective SR frameworks. The proposed AT-SELP SR and AT-SR frameworks proved to be flexible by integrating a Maximum A Posteriori (MAP)-based SR algorithm as well as a fast two-stage Fusion-Restoration (FR) SR estimator. By adopting the proposed selective SR frameworks, simulation results show significant reduction on average in computational complexity with comparable visual quality in terms of quantitative metrics such as PSNR, SNR or MAE gains, and subjective assessment. The third part of this thesis proposes a Perceptually Weighted (WP) SR technique that incorporates unequal weighting parameters in the cost function of iterative SR problems. The proposed approach is inspired by the unequal processing of the Human Visual System (HVS) to different local image features in an image. Simulation results show an enhanced reconstruction quality and faster convergence rates when applied to the MAP-based and FR-based SR schemes.
This work explores how flexible electronics and display technology can be applied to develop new biomedical devices for medical, biological, and life science applications. It demonstrates how new biomedical devices can be manufactured by only modifying or personalizing the upper layers of a conventional thin film transistor (TFT) display process. This personalization was applied first to develop and demonstrate the world's largest flexible digital x-ray detector for medical and industrial imaging, and the world's first flexible ISFET pH biosensor using TFT technology. These new, flexible, digital x-ray detectors are more durable than conventional glass substrate x-ray detectors, and also can conform to the surface of the object being imaged. The new flexible ISFET pH biosensors are >10X less expensive to manufacture than comparable CMOS-based ISFETs and provide a sensing area that is orders of magnitude larger than CMOS-based ISFETs. This allows for easier integration with area intensive chemical and biological recognition material as well as allow for a larger number of unique recognition sites for low cost multiple disease and pathogen detection.
The flexible x-ray detector technology was then extended to demonstrate the viability of a new technique to seamlessly combine multiple smaller flexible x-ray detectors into a single very large, ultimately human sized, composite x-ray detector for new medical imaging applications such as single-exposure, low-dose, full-body digital radiography. Also explored, is a new approach to increase the sensitivity of digital x-ray detectors by selectively disabling rows in the active matrix array that are not part of the imaged region. It was then shown how high-resolution, flexible, organic light-emitting diode display (OLED) technology can be used to selectively stimulate and/or silence small groups of neurons on the cortical surface or within the deep brain as a potential new tool to diagnose and treat, as well as understand, neurological diseases and conditions. This work also explored the viability of a new miniaturized high sensitivity fluorescence measurement-based lab-on-a-chip optical biosensor using OLED display and a-Si:H PiN photodiode active matrix array technology for point-of-care diagnosis of multiple disease or pathogen biomarkers in a low cost disposable configuration.
Development of New Front Side Metallization Method of Aluminum Electroplating for Silicon Solar Cell
In this thesis, the methods of aluminum electroplating in an ionic liquid for silicon solar cell front side metallization were studied. It focused on replacing the current silver screen printing with an alternative metallization technology using a low-cost Earth-abundant metal for mass production, due to the high cost and limited availability of silver. A conventional aluminum electroplating method was employed for silicon solar cells fabrication on both p-type and n-type substrates. The highest efficiency of 17.9% was achieved in the n-type solar cell with a rear junction, which is comparable to that of the same structure cell with screen printed silver electrodes from industrial production lines. It also showed better spiking resistant performance than the common structure p-type solar cell. Further efforts were put on the development of a novel light-induced plating of aluminum technique. The aluminum was deposited directly on a silicon substrate without the assistance of a conductive seed layer, thus simplified and reduced the process cost. The plated aluminum has good adhesion to the silicon surface with the resistivity as low as 4×10–6 -cm. A new demo tool was designed and set up for the light-induced plating experiment, aiming to utilize this technique in large-size solar cells fabrication and mass production. Besides the metallization methods, a comprehensive sensitivity analysis for the efficiency dispersion in the production of crystalline-Si solar cells was presented based on numerical simulations. Temperature variation in the diffusion furnace was the most significant cause of the efficiency dispersion. It was concluded that a narrow efficiency range of ±0.5% absolute is achievable if the emitter diffusion temperature is confined to a 13˚C window, while other cell parameters vary within their normal windows. Possible methods to minimize temperature variation in emitter diffusion were proposed.
Diagnostic and Therapeutic MEMS (Micro-Electro-Mechanical Systems) Devices for the Identification and Treatment of Human Disease
Early detection and treatment of disease is paramount for improving human health and wellness. Micro-scale devices promote new opportunities for the rapid, cost-effective, and accurate identification of altered biological states indicative of disease early-onset; these devices function at a scale more sensitive to numerous biological processes. The application of Micro-Electro-Mechanical Systems (MEMS) in biomedical settings has recently emerged and flourished over course of the last two decades, requiring a deep understanding of material biocompatibility, biosensing sensitively/selectively, biological constraints for artificial tissue/organ replacement, and the regulations in place to ensure device safety. Capitalizing on the inherent physical differences between cancerous and healthy cells, our ultra-thin silicone membrane enables earlier identification of bladder cancer—with a 70% recurrence rate. Building on this breakthrough, we have devised an array to multiplex this sample-analysis in real-time as well as expanding beyond bladder cancer. The introduction of new materials—with novel properties—to augment current and create innovative medical implants requires the careful analysis of material impact on cellular toxicity, mutagenicity, reactivity, and stability. Finally, the achievement of replacing defective biological systems with implanted artificial equivalents that must function within the same biological constraints, have consistent reliability, and ultimately show the promise of improving human health as demonstrated by our hydrogel check valve. The ongoing proliferation, expanding prevalence, and persistent improvement in MEMS devices through greater sensitivity, specificity, and integration with biological processes will undoubtedly bolster medical science with novel MEMS-based diagnostics and therapeutics.