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Each year, 30,000 patients obtain transplants. To prevent graft rejection, immunosuppressants such as tacrolimus are prescribed. Due to tacrolimus's narrow therapeutic range, a dose that is too low places patients at risk for transplant rejection, but too high of a dose leads to kidney failure. The de facto method for

Each year, 30,000 patients obtain transplants. To prevent graft rejection, immunosuppressants such as tacrolimus are prescribed. Due to tacrolimus's narrow therapeutic range, a dose that is too low places patients at risk for transplant rejection, but too high of a dose leads to kidney failure. The de facto method for monitoring of transplant patient health is bimonthly blood draws, which are cumbersome, painful, and difficult to translate into urgently needed dosage changes in a timely manner. To improve long-term transplant survival rates, we propose a finger-prick sensor that will provide patients and healthcare providers with a measurement of tacrolimus, immune health (through IL-12), and kidney damage (through cystatin C) levels 100 times more frequently than the status quo. Additionally, patient quality of life will be improved due to reduction in time and pain associated with blood draws. Optimal binding frequencies for each marker were found. However, due to limitations with EIS, the integration of the detection of the three markers into one multimarker sensing platform has not yet been realized. To this end, impedance-time tests were run on each marker along with different antibodies, and optimal times of each marker were determined to be 17s, 6s, and 2s, for tacrolimus, cystatin c, and IL-12, respectively (n=6). The integration of impedance-time analysis with traditional EIS methodologies has the potential to enable multi-marker analysis by analyzing binding kinetics on a single electrode with respect to time. Thus, our results provide unique insight into possibilities to improve and facilitate detection of multiple markers not only for the sensor for solid organ transplant patients, but for the monitoring of patients with disease that also entail the observation of multiple markers. Furthermore, the use of impedance-time testing also provides the ability for another way to optimize accuracy/precision of marker detection because it specifies a particular time, in addition to a particular optimal binding frequency, at which to measure concentration.
ContributorsDoshi, Meera Kshitij (Author) / LaBelle, Jeffrey (Thesis director) / Steidley, Eric (Committee member) / Harrington Bioengineering Program (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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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

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
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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

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
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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

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
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Description
Improved pancreatic cancer diagnostic technology has the potential to improve patient prognosis by increasing cancer screening rates and encouraging early detection of the cancer. To increase the sensitivity and specificity while decreasing the cost and time investment, the emerging detection method of electrochemical impedance spectroscopy (EIS) was tested to detect

Improved pancreatic cancer diagnostic technology has the potential to improve patient prognosis by increasing cancer screening rates and encouraging early detection of the cancer. To increase the sensitivity and specificity while decreasing the cost and time investment, the emerging detection method of electrochemical impedance spectroscopy (EIS) was tested to detect two pancreatic cancer specific biomarkers. The antibodies of carcinoembryonic antigen and quiescin sulfhydryl oxidase 1 were immobilized individually to gold disk electrodes and tested for binding to their respective antigens. An AC signal of varying potential and a wide frequency sweep was applied to the electrode system and the resulting imaginary impedance values were analyzed. Based off of the highest slope and R-squared values of the collected impedance values, the optimal binding frequencies of QSOX1 and CEA with their antibodies was determined to be 97.66 Hz and 17.44 Hz, respectively. EIS was also used to test for potential multimarker detection by coimmobilizing anti-CEA and anti-QSOX1 to the surface of gold disk electrodes. Each system's impedance response was correlated to the physiological concentration range of CEA and QSOX1 individually. The resulting impedance and concentration calibration curves had R-squared values of 0.78 and 0.79 for the calculated QSOX1 and CEA, respectively. Both markers showed similar trends between the calculated and actual calibration curves for each marker. The imaginary impedance output lacks two independent peaks for the distinct optimal binding frequencies of both biomarkers after signal subtraction and show a large shift in optimal frequencies. From analyzing the co-immobilization data for the calculated and experimentally determined calibration curves of CEA and QSOX1, both curves had different correlation values between imaginary impedance values and concentration. Add and subtracting the experimental and calculated co-immobilization, QSOX1, and CEA signals suggest an oversaturation of QSOX1 used during the experiments.
ContributorsMalla, Akshara (Co-author) / Murali, Keerthana (Co-author) / LaBelle, Jeffrey (Thesis director) / Lin, Chi-En (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
A point of care glucose sensor using electrochemical impedance spectroscopy (EIS) with a glutaraldehyde-linked enzyme shows promise as an effective biosensor platform. This report details the characterization of various factors on optimal binding frequency (OBF) and sensor performance to better prepare the sensor for future experimentation. Utilizing a screen printed

A point of care glucose sensor using electrochemical impedance spectroscopy (EIS) with a glutaraldehyde-linked enzyme shows promise as an effective biosensor platform. This report details the characterization of various factors on optimal binding frequency (OBF) and sensor performance to better prepare the sensor for future experimentation. Utilizing a screen printed carbon electrode, the necessary amount of glucose oxidase was determined to be 10 mg/mL. Binding time trials ranging from 1-3 minutes demonstrated that 1.5 minutes was the optimal binding time. This timeframe produced the strongest impedance response at each glucose concentration. Using this enzyme concentration and binding time, the native OBF of the biosensor was found to be 1.18 Hz using vector analysis. Temperature testing showed little change in OBF in sensors exposed to 4 \u00B0C through 43.3 \u00B0C. Only exposure to 60 \u00B0C resulted in rapid OBF change which was likely due to glucose oxidase becoming denatured. Humidity tests showed little change in OBF and sensor performance between sensors prepared at the humidities of 7.5%, 10.625% and 16.5% humidity. Alternatively, solutions containing common interference molecules such as uric acid, acetaminophen, and ascorbic acid resulted in a highly shifted OBF and drastically reduced signal.
ContributorsMatloff, Daniel (Co-author) / Khanwalker, Mukund (Co-author) / Johns, Jared (Co-author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Lin, Chi (Committee member) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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Description
As of today, there does not exist a cheap diagnostic for lactate for use in trauma centers. $671 billion are spent on trauma accidents and emergency rooms, with money focused on treatments such as YSI and ELISA, costing $1500 and $200, respectively. Gold disk electrodes were used to immobilize lactate

As of today, there does not exist a cheap diagnostic for lactate for use in trauma centers. $671 billion are spent on trauma accidents and emergency rooms, with money focused on treatments such as YSI and ELISA, costing $1500 and $200, respectively. Gold disk electrodes were used to immobilize lactate dehydrogenase and glucose oxidase, with electrochemical impedance spectroscopy (EIS) used as the method for detection. Two lactate experimental runs were completed with data detailing a linear model and positive correlation for imaginary impedance and concentration, and one glucose experimental run was completed proving that a continuous system can be completed accounting for reaction and consumption using EIS, a process previously not done before.
ContributorsEltohamy, Omar Khaled (Author) / LaBelle, Jeffrey (Thesis director) / Lin, Chi-En (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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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

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