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- Genre: Doctoral Dissertation
- Creators: Goryll, Michael
Description
Over the past several decades, there has been a growing interest in the use of fluorescent probes in low-cost diagnostic devices for resource-limited environments. This dissertation details the design, development, and deployment of an inexpensive, multiplexed, and quantitative, fluorescence-based lateral flow immunoassay platform, in light of the specific constraints associated with resource-limited settings.
This effort grew out of the need to develop a highly sensitive, field-deployable platform to be used as a primary screening and early detection tool for serologic biomarkers for the high-risk human papillomavirus (hrHPV) infection. A hrHPV infection is a precursor for developing high-grade cervical intraepithelial neoplasia (CIN 2/3+). Early detection requires high sensitivity and a low limit-of-detection (LOD). To this end, the developed platform (DxArray) takes advantage of the specificity of immunoassays and the selectivity of fluorescence for early disease detection. The long term goal is to improve the quality of life for several hundred million women globally, at risk of being infected with hrHPV.
The developed platform uses fluorescent labels over the gold-standard colorimetric labels in a compact, high-sensitivity lateral flow assay configuration. It is also compatible with POC settings as it substitutes expensive and bulky light sources for LEDs, low-light CMOS cameras, and photomultiplier tubes for photodiodes, in a transillumination architecture, and eliminates the need for expensive focusing/transfer optics. The platform uses high-quality interference filters at less than $1 each, enabling a rugged and robust design suitable for field use.
The limit of detection (LOD) of the developed platform is within an order of magnitude of centralized laboratory diagnostic instruments. It enhances the LOD of absorbance or reflectometric and visual readout lateral flow assays by 2 - 3 orders of magnitude. This system could be applied toward any chemical or bioanalytical procedure that requires a high performance at low-cost.
The knowledge and techniques developed in this effort is relevant to the community of researchers and industry developers looking to deploy inexpensive, quantitative, and highly sensitive diagnostic devices to resource-limited settings.
This effort grew out of the need to develop a highly sensitive, field-deployable platform to be used as a primary screening and early detection tool for serologic biomarkers for the high-risk human papillomavirus (hrHPV) infection. A hrHPV infection is a precursor for developing high-grade cervical intraepithelial neoplasia (CIN 2/3+). Early detection requires high sensitivity and a low limit-of-detection (LOD). To this end, the developed platform (DxArray) takes advantage of the specificity of immunoassays and the selectivity of fluorescence for early disease detection. The long term goal is to improve the quality of life for several hundred million women globally, at risk of being infected with hrHPV.
The developed platform uses fluorescent labels over the gold-standard colorimetric labels in a compact, high-sensitivity lateral flow assay configuration. It is also compatible with POC settings as it substitutes expensive and bulky light sources for LEDs, low-light CMOS cameras, and photomultiplier tubes for photodiodes, in a transillumination architecture, and eliminates the need for expensive focusing/transfer optics. The platform uses high-quality interference filters at less than $1 each, enabling a rugged and robust design suitable for field use.
The limit of detection (LOD) of the developed platform is within an order of magnitude of centralized laboratory diagnostic instruments. It enhances the LOD of absorbance or reflectometric and visual readout lateral flow assays by 2 - 3 orders of magnitude. This system could be applied toward any chemical or bioanalytical procedure that requires a high performance at low-cost.
The knowledge and techniques developed in this effort is relevant to the community of researchers and industry developers looking to deploy inexpensive, quantitative, and highly sensitive diagnostic devices to resource-limited settings.
ContributorsObahiagbon, Uwadiae (Author) / Blain Christen, Jennifer M (Thesis advisor) / Anderson, Karen S (Committee member) / Goryll, Michael (Committee member) / Smith, Barbara S. (Committee member) / Arizona State University (Publisher)
Created2018
Description
Mechanical properties of cells are important in maintaining physiological functions of biological systems. Quantitative measurement and analysis of mechanical properties can help understand cellular mechanics and its functional relevance and discover physical biomarkers for diseases monitoring and therapeutics.
This dissertation presents a work to develop optical methods for studying cell mechanics which encompasses four applications. Surface plasmon resonance microscopy based optical method has been applied to image intracellular motions and cell mechanical motion. This label-free technique enables ultrafast imaging with extremely high sensitivity in detecting cell deformation. The technique was first applied to study intracellular transportation. Organelle transportation process and displacement steps of motor protein can be tracked using this method. The second application is to study heterogeneous subcellular membrane displacement induced by membrane potential (de)polarization. The application can map the amplitude and direction of cell deformation. The electromechanical coupling of mammalian cells was also observed. The third application is for imaging electrical activity in single cells with sub-millisecond resolution. This technique can fast record actions potentials and also resolve the fast initiation and propagation of electromechanical signals within single neurons. Bright-field optical imaging approach has been applied to the mechanical wave visualization that associated with action potential in the fourth application. Neuron-to-neuron viability of membrane displacement was revealed and heterogeneous subcellular response was observed.
All these works shed light on the possibility of using optical approaches to study millisecond-scale and sub-nanometer-scale mechanical motions. These studies revealed ultrafast and ultra-small mechanical motions at the cellular level, including motor protein-driven motions and electromechanical coupled motions. The observations will help understand cell mechanics and its biological functions. These optical approaches will also become powerful tools for elucidating the interplay between biological and physical functions.
This dissertation presents a work to develop optical methods for studying cell mechanics which encompasses four applications. Surface plasmon resonance microscopy based optical method has been applied to image intracellular motions and cell mechanical motion. This label-free technique enables ultrafast imaging with extremely high sensitivity in detecting cell deformation. The technique was first applied to study intracellular transportation. Organelle transportation process and displacement steps of motor protein can be tracked using this method. The second application is to study heterogeneous subcellular membrane displacement induced by membrane potential (de)polarization. The application can map the amplitude and direction of cell deformation. The electromechanical coupling of mammalian cells was also observed. The third application is for imaging electrical activity in single cells with sub-millisecond resolution. This technique can fast record actions potentials and also resolve the fast initiation and propagation of electromechanical signals within single neurons. Bright-field optical imaging approach has been applied to the mechanical wave visualization that associated with action potential in the fourth application. Neuron-to-neuron viability of membrane displacement was revealed and heterogeneous subcellular response was observed.
All these works shed light on the possibility of using optical approaches to study millisecond-scale and sub-nanometer-scale mechanical motions. These studies revealed ultrafast and ultra-small mechanical motions at the cellular level, including motor protein-driven motions and electromechanical coupled motions. The observations will help understand cell mechanics and its biological functions. These optical approaches will also become powerful tools for elucidating the interplay between biological and physical functions.
ContributorsYang, Yunze (Author) / Tao, Nongjian (Thesis advisor) / Wang, Shaopeng (Committee member) / Goryll, Michael (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2016
Description
Silicon carbide (SiC) has always been considered as an excellent material for high temperature and high power devices. Since SiC is the only compound semiconductor whose native oxide is silicon dioxide (SiO2), it puts SiC in a unique position. Although SiC metal oxide semiconductor (MOS) technology has made significant progress in recent years, there are still a number of issues to be overcome before more commercial SiC devices can enter the market. The prevailing issues surrounding SiC MOSFET devices are the low channel mobility, the low quality of the oxide layer and the high interface state density at the SiC/SiO2 interface. Consequently, there is a need for research to be performed in order to have a better understanding of the factors causing the poor SiC/SiO2 interface properties. In this work, we investigated the generation lifetime in SiC materials by using the pulsed metal oxide semiconductor (MOS) capacitor method and measured the interface state density distribution at the SiC/SiO2 interface by using the conductance measurement and the high-low frequency capacitance technique. These measurement techniques have been performed on n-type and p-type SiC MOS capacitors. In the course of our investigation, we observed fast interface states at semiconductor-dielectric interfaces in SiC MOS capacitors that underwent three different interface passivation processes, such states were detected in the nitrided samples but not observed in PSG-passivated samples. This result indicate that the lack of fast states at PSG-passivated interface is one of the main reasons for higher channel mobility in PSG MOSFETs. In addition, the effect of mobile ions in the oxide on the response time of interface states has been investigated. In the last chapter we propose additional methods of investigation that can help elucidate the origin of the particular interface states, enabling a more complete understanding of the SiC/SiO2 material system.
ContributorsKao, Wei-Chieh (Author) / Goryll, Michael (Thesis advisor) / Chowdhury, Srabanti (Committee member) / Yu, Hongbin (Committee member) / Marinella, Matthew (Committee member) / Arizona State University (Publisher)
Created2015
Description
Programmable metallization cell (PMC) technology employs the mechanisms of metal ion transport in solid electrolytes (SE) and electrochemical redox reactions in order to form metallic electrodeposits. When a positive bias is applied to an anode opposite to a cathode, atoms at the anode are oxidized to ions and dissolve into the SE. Under the influence of the electric field, the ions move to the cathode and become reduced to form the electrodeposits. These electrodeposits are filamentary in nature and persistent, and since they are metallic can alter the physical characteristics of the material on which they are formed. PMCs can be used as next generation memories, radio frequency (RF) switches and physical unclonable functions (PUFs).
The morphology of the filaments is impacted by the biasing conditions. Under a relatively high applied electric field, they form as dendritic elements with a low fractal dimension (FD), whereas a low electric field leads to high FD features. Ion depletion effects in the SE due to low ion diffusivity/mobility also influences the morphology by limiting the ion supply into the growing electrodeposit.
Ion transport in SE is due to hopping transitions driven by drift and diffusion force. A physical model of ion hopping with Brownian motion has been proposed, in which the ion transitions are random when time window is larger than characteristic time. The random growth process of filaments in PMC adds entropy to the electrodeposition, which leads to random features in the dendritic patterns. Such patterns has extremely high information capacity due to the fractal nature of the electrodeposits.
In this project, lateral-growth PMCs were fabricated, whose LRS resistance is less than 10Ω, which can be used as RF switches. Also, an array of radial-growth PMCs was fabricated, on which multiple dendrites, all with different shapes, could be grown simultaneously. Those patterns can be used as secure keys in PUFs and authentication can be performed by optical scanning.
A kinetic Monte Carlo (KMC) model is developed to simulate the ion transportation in SE under electric field. The simulation results matched experimental data well that validated the ion hopping model.
The morphology of the filaments is impacted by the biasing conditions. Under a relatively high applied electric field, they form as dendritic elements with a low fractal dimension (FD), whereas a low electric field leads to high FD features. Ion depletion effects in the SE due to low ion diffusivity/mobility also influences the morphology by limiting the ion supply into the growing electrodeposit.
Ion transport in SE is due to hopping transitions driven by drift and diffusion force. A physical model of ion hopping with Brownian motion has been proposed, in which the ion transitions are random when time window is larger than characteristic time. The random growth process of filaments in PMC adds entropy to the electrodeposition, which leads to random features in the dendritic patterns. Such patterns has extremely high information capacity due to the fractal nature of the electrodeposits.
In this project, lateral-growth PMCs were fabricated, whose LRS resistance is less than 10Ω, which can be used as RF switches. Also, an array of radial-growth PMCs was fabricated, on which multiple dendrites, all with different shapes, could be grown simultaneously. Those patterns can be used as secure keys in PUFs and authentication can be performed by optical scanning.
A kinetic Monte Carlo (KMC) model is developed to simulate the ion transportation in SE under electric field. The simulation results matched experimental data well that validated the ion hopping model.
ContributorsYu, Weijie (Author) / Kozicki, Michael N (Thesis advisor) / Barnaby, Hugh (Thesis advisor) / Diaz, Rodolfo (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2015
Description
Solid-state nanopore research, used in the field of biomolecule detection and separation, has developed rapidly during the last decade. An electric field generated from the nanopore membrane to the aperture surface by a bias voltage can be used to electrostatically control the transport of charges. This results in ionic current rectification that can be used for applications such as biomolecule filtration and DNA sequencing.
In this doctoral research, a voltage bias was applied on the device silicon layer of Silicon-on-Insulator (SOI) cylindrical single nanopore to analyze how the perpendicular gate electrical field affected the ionic current through the pore. The nanopore was fabricated using electron beam lithography (EBL) and reactive ion etching (RIE) which are standard CMOS processes and can be integrated into any electronic circuit with massive production. The long cylindrical pore shape provides a larger surface area inside the aperture compared to other nanopores whose surface charge is of vital importance to ion transport.
Ionic transport through the nanopore was characterized by measuring the ionic conductance of the nanopore in aqueous hydrochloric acid and potassium chloride solutions under field effect modulation. The nanopores were separately coated with negatively charged thermal silicon oxide and positively charged aluminum oxide using Atomic Layer Deposition. Both layers worked as electrical insulation layers preventing leakage current once the substrate bias was applied. Different surface charges also provided different counterion-coion configurations. The transverse conductance of the nanopore at low electrolyte concentrations (<10-4 M) changed with voltage bias when the Debye length was comparable to the dimensions of the nanopore.
Ionic transport through nanopores coated with polyelectrolyte (PE) brushes were also investigated in ionic solutions with various pH values using Electrochemical Impedance spectroscopy (EIS). The pH sensitive poly[2–(dimethylamino) ethyl methacrylate] (PDMAEMA) PE brushes were integrated on the inner walls as well as the surface of the thermal oxidized SOI cylindrical nanopore using surface-initiated atom transfer radical polymerization (SI-ATRP). An equivalent circuit model was developed to extract conductive and resistive values of the nanopore in ionic solutions. The ionic conductance of PE coated nanopore was effectively rectified by varying the pH and gate bias.
In this doctoral research, a voltage bias was applied on the device silicon layer of Silicon-on-Insulator (SOI) cylindrical single nanopore to analyze how the perpendicular gate electrical field affected the ionic current through the pore. The nanopore was fabricated using electron beam lithography (EBL) and reactive ion etching (RIE) which are standard CMOS processes and can be integrated into any electronic circuit with massive production. The long cylindrical pore shape provides a larger surface area inside the aperture compared to other nanopores whose surface charge is of vital importance to ion transport.
Ionic transport through the nanopore was characterized by measuring the ionic conductance of the nanopore in aqueous hydrochloric acid and potassium chloride solutions under field effect modulation. The nanopores were separately coated with negatively charged thermal silicon oxide and positively charged aluminum oxide using Atomic Layer Deposition. Both layers worked as electrical insulation layers preventing leakage current once the substrate bias was applied. Different surface charges also provided different counterion-coion configurations. The transverse conductance of the nanopore at low electrolyte concentrations (<10-4 M) changed with voltage bias when the Debye length was comparable to the dimensions of the nanopore.
Ionic transport through nanopores coated with polyelectrolyte (PE) brushes were also investigated in ionic solutions with various pH values using Electrochemical Impedance spectroscopy (EIS). The pH sensitive poly[2–(dimethylamino) ethyl methacrylate] (PDMAEMA) PE brushes were integrated on the inner walls as well as the surface of the thermal oxidized SOI cylindrical nanopore using surface-initiated atom transfer radical polymerization (SI-ATRP). An equivalent circuit model was developed to extract conductive and resistive values of the nanopore in ionic solutions. The ionic conductance of PE coated nanopore was effectively rectified by varying the pH and gate bias.
ContributorsWang, Xiaofeng (Author) / Goryll, Michael (Thesis advisor) / Thornton, Trevor J (Committee member) / Christen, Jennifer M (Committee member) / Yu, Hongbin (Committee member) / Arizona State University (Publisher)
Created2015
Description
To date, the most popular and dominant material for commercial solar cells is
crystalline silicon (or wafer-Si). It has the highest cell efficiency and cell lifetime out
of all commercial solar cells. Although the potential of crystalline-Si solar cells in
supplying energy demands is enormous, their future growth will likely be constrained
by two major bottlenecks. The first is the high electricity input to produce
crystalline-Si solar cells and modules, and the second is the limited supply of silver
(Ag) reserves. These bottlenecks prevent crystalline-Si solar cells from reaching
terawatt-scale deployment, which means the electricity produced by crystalline-Si
solar cells would never fulfill a noticeable portion of our energy demands in the future.
In order to solve the issue of Ag limitation for the front metal grid, aluminum (Al)
electroplating has been developed as an alternative metallization technique in the
fabrication of crystalline-Si solar cells. The plating is carried out in a
near-room-temperature ionic liquid by means of galvanostatic electrolysis. It has been
found that dense, adherent Al deposits with resistivity in the high 10^–6 ohm-cm range
can be reproducibly obtained directly on Si substrates and nickel seed layers. An
all-Al Si solar cell, with an electroplated Al front electrode and a screen-printed Al
back electrode, has been successfully demonstrated based on commercial p-type
monocrystalline-Si solar cells, and its efficiency is approaching 15%. Further
optimization of the cell fabrication process, in particular a suitable patterning
technique for the front silicon nitride layer, is expected to increase the efficiency of
the cell to ~18%. This shows the potential of Al electroplating in cell metallization is
promising and replacing Ag with Al as the front finger electrode is feasible.
crystalline silicon (or wafer-Si). It has the highest cell efficiency and cell lifetime out
of all commercial solar cells. Although the potential of crystalline-Si solar cells in
supplying energy demands is enormous, their future growth will likely be constrained
by two major bottlenecks. The first is the high electricity input to produce
crystalline-Si solar cells and modules, and the second is the limited supply of silver
(Ag) reserves. These bottlenecks prevent crystalline-Si solar cells from reaching
terawatt-scale deployment, which means the electricity produced by crystalline-Si
solar cells would never fulfill a noticeable portion of our energy demands in the future.
In order to solve the issue of Ag limitation for the front metal grid, aluminum (Al)
electroplating has been developed as an alternative metallization technique in the
fabrication of crystalline-Si solar cells. The plating is carried out in a
near-room-temperature ionic liquid by means of galvanostatic electrolysis. It has been
found that dense, adherent Al deposits with resistivity in the high 10^–6 ohm-cm range
can be reproducibly obtained directly on Si substrates and nickel seed layers. An
all-Al Si solar cell, with an electroplated Al front electrode and a screen-printed Al
back electrode, has been successfully demonstrated based on commercial p-type
monocrystalline-Si solar cells, and its efficiency is approaching 15%. Further
optimization of the cell fabrication process, in particular a suitable patterning
technique for the front silicon nitride layer, is expected to increase the efficiency of
the cell to ~18%. This shows the potential of Al electroplating in cell metallization is
promising and replacing Ag with Al as the front finger electrode is feasible.
ContributorsSun, Wen-Cheng (Author) / Tao, Meng (Thesis advisor) / Vasileska, Dragica (Committee member) / Yu, Hongbin (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2016
Description
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.
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.
ContributorsGuan, Yan (Author) / Tao, Nongjian (Thesis advisor) / LaBaer, Joshua (Committee member) / Goryll, Michael (Committee member) / Wang, Shaopeng (Committee member) / Arizona State University (Publisher)
Created2015
Description
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.
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.
ContributorsLiu, Bobo (Author) / Ferry, David K. (Thesis advisor) / Akis, Richard (Committee member) / Saraniti, Marco (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2015
Description
Biosensors aiming at detection of target analytes, such as proteins, microbes, virus, and toxins, are widely needed for various applications including detection of chemical and biological warfare (CBW) agents, biomedicine, environmental monitoring, and drug screening. Surface Plasmon Resonance (SPR), as a surface-sensitive analytical tool, can very sensitively respond to minute changes of refractive index occurring adjacent to a metal film, offering detection limits up to a few ppt (pg/mL). Through SPR, the process of protein adsorption may be monitored in real-time, and transduced into an SPR angle shift. This unique technique bypasses the time-consuming, labor-intensive labeling processes, such as radioisotope and fluorescence labeling. More importantly, the method avoids the modification of the biomarker’s characteristics and behaviors by labeling that often occurs in traditional biosensors. While many transducers, including SPR, offer high sensitivity, selectivity is determined by the bio-receptors. In traditional biosensors, the selectivity is provided by bio-receptors possessing highly specific binding affinity to capture target analytes, yet their use in biosensors are often limited by their relatively-weak binding affinity with analyte, non-specific adsorption, need for optimization conditions, low reproducibility, and difficulties integrating onto the surface of transducers. In order to circumvent the use of bio-receptors, the competitive adsorption of proteins, termed the Vroman effect, is utilized in this work. The Vroman effect was first reported by Vroman and Adams in 1969. The competitive adsorption targeted here occurs among different proteins competing to adsorb to a surface, when more than one type of protein is present. When lower-affinity proteins are adsorbed on the surface first, they can be displaced by higher-affinity proteins arriving at the surface at a later point in time. Moreover, only low-affinity proteins can be displaced by high-affinity proteins, typically possessing higher molecular weight, yet the reverse sequence does not occur. The SPR biosensor based on competitive adsorption is successfully demonstrated to detect fibrinogen and thyroglobulin (Tg) in undiluted human serum and copper ions in drinking water through the denatured albumin.
ContributorsWang, Ran (Author) / Chae, Junseok (Thesis advisor) / Bakkaloglu, Bertan (Committee member) / Tsow, Tsing (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2015
Description
The microelectronics technology has seen a tremendous growth over the past sixty years. The advancements in microelectronics, which shows the capability of yielding highly reliable and reproducible structures, have made the mass production of integrated electronic components feasible. Miniaturized, low-cost, and accurate sensors became available due to the rise of the microelectronics industry. A variety of sensors are being used extensively in many portable applications. These sensors are promising not only in research area but also in daily routine applications.
However, many sensing systems are relatively bulky, complicated, and expensive and main advantages of new sensors do not play an important role in practical applications. Many challenges arise due to intricacies for sensor packaging, especially operation in a solution environment. Additional problems emerge when interfacing sensors with external off-chip components. A large amount of research in the field of sensors has been focused on how to improve the system integration.
This work presents new methods for the design, fabrication, and integration of sensor systems. This thesis addresses these challenges, for example, interfacing microelectronic system to a liquid environment and developing a new technique for impedimetric measurement. This work also shows a new design for on-chip optical sensor without any other extra components or post-processing.
However, many sensing systems are relatively bulky, complicated, and expensive and main advantages of new sensors do not play an important role in practical applications. Many challenges arise due to intricacies for sensor packaging, especially operation in a solution environment. Additional problems emerge when interfacing sensors with external off-chip components. A large amount of research in the field of sensors has been focused on how to improve the system integration.
This work presents new methods for the design, fabrication, and integration of sensor systems. This thesis addresses these challenges, for example, interfacing microelectronic system to a liquid environment and developing a new technique for impedimetric measurement. This work also shows a new design for on-chip optical sensor without any other extra components or post-processing.
ContributorsLuo, Tao (Author) / Blain Christen, Jennifer (Thesis advisor) / Song, Hongjiang (Committee member) / Goryll, Michael (Committee member) / Yu, Hongbin (Committee member) / Arizona State University (Publisher)
Created2015