Matching Items (6)
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- All Subjects: Sensors
- All Subjects: Microfluidics
- Creators: LaBelle, Jeffrey
Description
Cellular heterogeneity is a key factor in various cellular processes as well as in disease development, especially associated with immune response and cancer progression. Cell-to-cell variability is considered to be one of the major obstacles in early detection and successful treatment of cancer. Most present technologies are based on bulk cell analysis, which results in averaging out the results acquired from a group of cells and hence missing important information about individual cells and their behavior. Understanding the cellular behavior at the single-cell level can help in obtaining a complete profile of the cell and to get a more in-depth knowledge of cellular processes. For example, measuring transmembrane fluxes oxygen can provide a direct readout of the cell metabolism.
The goal of this thesis is to design, optimize and implement a device that can measure the oxygen consumption rate (OCR) of live single cells. A microfluidic device has been designed with the ability to rapidly seal and unseal microchambers containing individual cells and an extracellular optical oxygen sensor for measuring the OCR of live single cells. The device consists of two parts, one with the sensor in microwells (top half) and the other with channels and cells trapped in Pachinko-type micro-traps (bottom half). When the two parts of the device are placed together the wells enclose each cell. Oil is flown in through the channels of the device to produce isolated and sealed microchamber around each cell. Different fluids can be flowed in and out of the device, alternating with oil, to rapidly switch between sealed and unsealed microenvironment around each cell. A fluorescent ratiometric dual pH and oxygen sensor is placed in each well. The thesis focuses on measuring changes in the oxygen consumption rate of each cell within a well. Live and dead cells are identified using a fluorescent live/dead cell assay. Finally, the technology is designed to be scalable for high-throughput applications by controlling the flow rate of the system and increasing the cell array density.
The goal of this thesis is to design, optimize and implement a device that can measure the oxygen consumption rate (OCR) of live single cells. A microfluidic device has been designed with the ability to rapidly seal and unseal microchambers containing individual cells and an extracellular optical oxygen sensor for measuring the OCR of live single cells. The device consists of two parts, one with the sensor in microwells (top half) and the other with channels and cells trapped in Pachinko-type micro-traps (bottom half). When the two parts of the device are placed together the wells enclose each cell. Oil is flown in through the channels of the device to produce isolated and sealed microchamber around each cell. Different fluids can be flowed in and out of the device, alternating with oil, to rapidly switch between sealed and unsealed microenvironment around each cell. A fluorescent ratiometric dual pH and oxygen sensor is placed in each well. The thesis focuses on measuring changes in the oxygen consumption rate of each cell within a well. Live and dead cells are identified using a fluorescent live/dead cell assay. Finally, the technology is designed to be scalable for high-throughput applications by controlling the flow rate of the system and increasing the cell array density.
ContributorsRodrigues, Meryl (Author) / Meldrum, Deirdre (Thesis advisor) / Kelbauskas, Laimonas (Committee member) / LaBelle, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2014
Description
Diabetes mellitus is a disease characterized by many chronic and acute conditions. With the prevalence and cost quickly increasing, we seek to improve on the current standard of care and create a rapid, label free sensor for glycated albumin (GA) index using electrochemical impedance spectroscopy (EIS). The antibody, anti-HA, was fixed to gold electrodes and a sine wave of sweeping frequencies was induced with a range of HA, GA, and GA with HA concentrations. Each frequency in the impedance sweep was analyzed for highest response and R-squared value. The frequency with both factors optimized is specific for both the antibody-antigen binding interactions with HA and GA and was determined to be 1476 Hz and 1.18 Hz respectively in purified solutions. The correlation slope between the impedance response and concentration for albumin (0 \u2014 5400 mg/dL of albumin) was determined to be 72.28 ohm/ln(mg/dL) with an R-square value of 0.89 with a 2.27 lower limit of detection. The correlation slope between the impedance response and concentration for glycated albumin (0 \u2014 108 mg/dL) was determined to be -876.96 ohm/ln(mg/dL) with an R-squared value of 0.70 with a 0.92 mg/dL lower limit of detection (LLD). The above data confirms that EIS offers a new method of GA detection by providing unique correlation with albumin as well as glycated albumin. The unique frequency response of GA and HA allows for modulation of alternating current signals so that several other markers important in the management of diabetes could be measured with a single sensor. Future work will be necessary to establish multimarker sensing on one electrode.
ContributorsEusebio, Francis Ang (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Growing concern over health risks associated with environmental contaminants has prompted an increase in the search for effective detection methods. The available options provide acceptable sensitivity and specificity, but with high purchase and maintenance costs. Herein, a low-cost, portable environmental contaminant sensor was developed using electrochemical techniques and an efficient hydrogel capture mechanism. The sensor operates with high sensitivity and maintains specificity without the added requirement of extensive electrode modification. Rather, specificity is obtained by choosing specific potential regions in which individual contaminants show reduction or oxidation activity. A calibration curve was generated showing the utility of the sensor in detecting gas compounds reliably in reference to a current state of the art sensor. Reusability of the sensor was also demonstrated with a cyclic exposure test in which response reversibility was observed. As such, the investigated sensor shows great promise as a replacement technology in the current environmental contaminant detector industry.
ContributorsMarch, Michael Stephen (Author) / LaBelle, Jeffrey (Thesis director) / Caplan, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
This paper summarizes the [1] ideas behind, [2] needs, [3] development, and [4] testing of 3D-printed sensor-stents known as Stentzors. This sensor was successfully developed entirely from scratch, tested, and was found to have an output of 3.2*10-6 volts per RMS pressure in pascals. This paper also recommends further work to render the Stentzor deployable in live subjects, including [1] further design optimization, [2] electrical isolation, [3] wireless data transmission, and [4] testing for aneurysm prevention.
ContributorsMeidinger, Aaron Michael (Author) / LaBelle, Jeffrey (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / Mechanical and Aerospace Engineering Program (Contributor)
Created2014-05
Description
Over the past fifty years, the development of sensors for biological applications has increased dramatically. This rapid growth can be attributed in part to the reduction in feature size, which the electronics industry has pioneered over the same period. The decrease in feature size has led to the production of microscale sensors that are used for sensing applications, ranging from whole-body monitoring down to molecular sensing. Unfortunately, sensors are often developed without regard to how they will be integrated into biological systems. The complexities of integration are underappreciated. Integration involves more than simply making electrical connections. Interfacing microscale sensors with biological environments requires numerous considerations with respect to the creation of compatible packaging, the management of biological reagents, and the act of combining technologies with different dimensions and material properties. Recent advances in microfluidics, especially the proliferation of soft lithography manufacturing methods, have established the groundwork for creating systems that may solve many of the problems inherent to sensor-fluidic interaction. The adaptation of microelectronics manufacturing methods, such as Complementary Metal-Oxide-Semiconductor (CMOS) and Microelectromechanical Systems (MEMS) processes, allows the creation of a complete biological sensing system with integrated sensors and readout circuits. Combining these technologies is an obstacle to forming complete sensor systems. This dissertation presents new approaches for the design, fabrication, and integration of microscale sensors and microelectronics with microfluidics. The work addresses specific challenges, such as combining commercial manufacturing processes into biological systems and developing microscale sensors in these processes. This work is exemplified through a feedback-controlled microfluidic pH system to demonstrate the integration capabilities of microscale sensors for autonomous microenvironment control.
ContributorsWelch, David (Author) / Blain Christen, Jennifer (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Frakes, David (Committee member) / LaBelle, Jeffrey (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2012
Description
Intracranial aneurysms, which form in the blood vessels of the brain, are particularly dangerous because of the importance and fragility of the human brain. When an intracranial aneurysm gets large it poses a significant risk of bursting and causing subarachnoid hemorrhaging (SAH), a possibly fatal condition. One possible treatment involves placing a stent in the vessel to act as a flow diverter. In this study we look at the hemodynamics of two geometries of idealized basilar tip aneurysms, at 2,3, and 4 ml/s pulsatile flow, at three different points in the cardiac cycle. The smaller model had neck and dome diameters of 2.67 mm and 4 mm respectively, while the larger aneurysm had neck and dome diameters of 3 mm and 6 mm respectively. Both diameters and the dome to neck ratio increased in the second model, representing growth over time. Flow was analyzed using stereoscopic particle image velocimetry (PIV) for both geometries in untreated models, as well as after treatment with a high porosity Enterprise stent (Codman and Shurtleff Inc.). Flow in the models was characterized by root mean square velocity in the aneurysm and neck plane, cross neck flow, max aneurysm vorticity, and total aneurysm kinetic energy. It was found that in the smaller aneurysm model (model 1), Enterprise stent treatment reduced all flow parameters substantially. The smallest reduction was in max vorticity, at 42.48%, and the largest in total kinetic energy, at 75.69%. In the larger model (model 2) there was a 52.18% reduction in cross neck flow, but a 167.28% increase in aneurysm vorticity. The other three parameters experienced little change. These results, along with observed velocity vector fields, indicate a noticeable diversion of flow away from the aneurysm in the stent treated model 1. Treatment in model 2 had a small flow diversion effect, but also altered flow in unpredictable ways, in some cases having a detrimental effect on aneurysm hemodynamics. The results of this study indicate that Enterprise stent treatment is only effective in small, relatively undeveloped aneurysm geometries, and waiting until an aneurysm has grown too large can eliminate this treatment option altogether.
ContributorsLindsay, James Bryan (Author) / Frakes, David (Thesis director) / LaBelle, Jeffrey (Committee member) / Nair, Priya (Committee member) / Barrett, The Honors College (Contributor) / School of Humanities, Arts, and Cultural Studies (Contributor)
Created2013-05