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Description
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

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.
ContributorsPodlevsky, Jennie Hewitt Appel (Author) / Chae, Junseok (Thesis advisor) / Goryll, Michael (Committee member) / Kozicki, Michael (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2018
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Description
This work describes efforts made toward the development of a compact, quantitative fluorescence-based multiplexed detection platform for point-of-care diagnostics. This includes the development of a microfluidic delivery and actuation system for multistep detection assays. Early detection of infectious diseases requires high sensitivity dependent on the precise actuation of fluids.

Methods

This work describes efforts made toward the development of a compact, quantitative fluorescence-based multiplexed detection platform for point-of-care diagnostics. This includes the development of a microfluidic delivery and actuation system for multistep detection assays. Early detection of infectious diseases requires high sensitivity dependent on the precise actuation of fluids.

Methods of fluid actuation were explored to allow delayed delivery of fluidic reagents in multistep detection lateral flow assays (LFAs). Certain hydrophobic materials such as wax were successfully implemented in the LFA with the use of precision dispensed valves. Sublimating materials such as naphthalene were also characterized along with the implementation of a heating system for precision printing of the valves.

Various techniques of blood fractionation were also investigated and this work demonstrates successful blood fractionation in an LFA. The fluid flow of reagents was also characterized and validated with the use of mathematical models and multiphysics modeling software. Lastly intuitive, user-friendly mobile and desktop applications were developed to interface the underlying Arduino software. The work advances the development of a system which successfully integrates all components of fluid separation and delivery along with highly sensitive detection and a user-friendly interface; the system will ultimately provide clinically significant diagnostics in a of point-of-care device.
ContributorsArafa, Hany M (Author) / Blain Christen, Jennifer M (Thesis advisor) / Goryll, Michael (Committee member) / Smith, Barbara (Committee member) / Arizona State University (Publisher)
Created2018
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Description
A single cell is the very fundamental element in an organism; however, it contains the most complicated and stochastic information, such as DNA, RNA, and protein expression. Thus, it is a necessity to study stochastic gene expression in order to discover the biosignatures at the single-cell level. The heterogeneous gene

A single cell is the very fundamental element in an organism; however, it contains the most complicated and stochastic information, such as DNA, RNA, and protein expression. Thus, it is a necessity to study stochastic gene expression in order to discover the biosignatures at the single-cell level. The heterogeneous gene expression of single cells from an isogenic cell population has already been studied for years. Yet to date, single-cell studies have been confined in a fashion of analyzing isolated single cells or a dilution of cells from the bulk-cell populations. These techniques or devices are limited by either the mechanism of cell lysis or the difficulties to target specific cells without harming neighboring cells.

This dissertation presents the development of a laser lysis chip combined with a two-photon laser system to perform single-cell lysis of single cells in situ from three-dimensional (3D) cell spheroids followed by analysis of the cell lysate with two-step reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The 3D spheroids were trapped in a well in the custom-designed laser lysis chip. Next, each single cell of interest in the 3D spheroid was identified and lysed one at a time utilizing a two-photon excited laser. After each cell lysis, the contents inside the target cell were released to the surrounding media and carried out to the lysate collector. Finally, the gene expression of each individual cell was measured by two-step RT-qPCR then spatially mapped back to its original location in the spheroids to construct a 3D gene expression map.

This novel technology and approach enables multiple gene expression measurements in single cells of multicellular organisms as well as cell-to-cell heterogeneous responses to the environment with spatial recognition. Furthermore, this method can be applied to study precancerous tissues for a better understanding of cancer progression and for identifying early tumor development.
ContributorsWang, Guozhen (Author) / Meldrum, Deirdre R (Thesis advisor) / Chao, Shih-hui (Committee member) / Wang, Hong (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2016
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Description
While SPICE circuit simulation software gives researchers and industry accurate information regarding the behavior and characteristics of circuits, the auditory effect of SPICE circuit simulation on audio circuits is not well documented. This project takes a thoroughly analyzed and popular audio effect circuit called the Ibanez Tubescreamer and simulates its

While SPICE circuit simulation software gives researchers and industry accurate information regarding the behavior and characteristics of circuits, the auditory effect of SPICE circuit simulation on audio circuits is not well documented. This project takes a thoroughly analyzed and popular audio effect circuit called the Ibanez Tubescreamer and simulates its distortion effect on a .wav file in order to hear the effect of SPICE simulation. Specifically, the TS-808 schematic is drawn in the SPICE program LTSPICE and simulated using generated sinusoids and recorded .wav files. Specific components are imported using .MODEL and .SUBCKT to accurately represent the diodes, bipolar transistors, op amps, and other components in order to hear how each component affects the response. Various transient responses are extracted as .wav files and assembled as figures in order to characterize the result of the circuit on the input. Once the actual circuit is built and debugged, all of the same transient analysis is applied and then compared to the SPICE simulation figures gathered in the digital simulation. These results are then compared along with a subjective hearing test of the digital simulation and analog circuit in order to test the validity of the SPICE simulations. The digital simulations reveal that the distortion follows the signature characteristics of Ibanez Tubescreamer which shows that SPICE simulation will give insight into the real effects of audio circuits modeled in SPICE programs. Diodes--such as Silicon, Germanium, Zener, Red LEDs and Blue LEDs--can dramatically change the waveforms and sound of the inputs within the circuit where as the Op-amps--such as the JRC4558, TL072, and NE5532--have little to no effect on the waveforms and subjective effects on the output .wav files. After building the circuit and hearing the difference between the analog circuit and digital simulation, the differences between the two are apparent but very similar in nature--proving that the SPICE simulation can give meaningful insight into the sound of the actual analog circuit. Some of the differences can be explained by the variance of equipment and environment used in recording and playback. Since this project did not use high fidelity audio recording equipment and consistency in the equipment used for playback, it is uncertain if the simulation and actual circuit could be classified as completely accurate. Any further work on the project would be recording and playing back in a constant environment and looking into a wider range of specific components instead of looking into one permutation.
ContributorsMacias, Cole Thomas (Author) / Goryll, Michael (Thesis director) / Yu, Shimeng (Committee member) / Electrical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12