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The purpose of this project was to examine the viability of protein biomarkers in pre-symptomatic detection of lung cancer. Regular screening has been shown to vastly improve patient survival outcome. Lung cancer currently has the highest occurrence and mortality of all cancers and so a means of screening would be

The purpose of this project was to examine the viability of protein biomarkers in pre-symptomatic detection of lung cancer. Regular screening has been shown to vastly improve patient survival outcome. Lung cancer currently has the highest occurrence and mortality of all cancers and so a means of screening would be highly beneficial. In this research, the biomarker neuron-specific enolase (Enolase-2, eno2), a marker of small-cell lung cancer, was detected at varying concentrations using electrochemical impedance spectroscopy in order to develop a mathematical model of predicting protein expression based on a measured impedance value at a determined optimum frequency. The extent of protein expression would indicate the possibility of the patient having small-cell lung cancer. The optimum frequency was found to be 459 Hz, and the mathematical model to determine eno2 concentration based on impedance was found to be y = 40.246x + 719.5 with an R2 value of 0.82237. These results suggest that this approach could provide an option for the development of small-cell lung cancer screening utilizing electrochemical technology.
ContributorsEvans, William Ian (Author) / LaBelle, Jeffrey (Thesis director) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA

The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.
ContributorsFauer, Chase Alexander (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still

With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still have some way to go before they are viable systems for drug delivery. One of the main reasons for this is a lack of fabrication processes and systems which produce monodisperse particles while also being feasible for industrialization [10]. This honors thesis investigates various microparticle fabrication techniques \u2014 two using mechanical agitation and one using fluid dynamics \u2014 with the long term goal of incorporating norepinephrine and adenosine into the particles for metabolic stimulatory purposes. It was found that mechanical agitation processes lead to large values for dispersity and the polydispersity index while fluid dynamics methods have the potential to create more uniform and predictable outcomes. The research concludes by needing further investigation into methods and prototype systems involving fluid dynamics methods; however, these systems yield promising results for fabricating monodisperse particles which have the potential to encapsulate a wide variety of therapeutic drugs.
ContributorsRiley, Levi Louis (Author) / Vernon, Brent (Thesis director) / VanAuker, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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Description
In this paper, β-estradiol was characterized utilizing electrochemical impedance spectroscopy (EIS) techniques for the purpose of developing a multi-marker fertility sensor. β-estradiol was immobilized onto the surface of gold disk electrodes to find the optimal binding frequency of estradiol and its respective antibody, anti-17β-estradiol, which was determined to be 37.46Hz.

In this paper, β-estradiol was characterized utilizing electrochemical impedance spectroscopy (EIS) techniques for the purpose of developing a multi-marker fertility sensor. β-estradiol was immobilized onto the surface of gold disk electrodes to find the optimal binding frequency of estradiol and its respective antibody, anti-17β-estradiol, which was determined to be 37.46Hz. At this frequency a logarithmic relationship between concentration and impedance (Z/ohm) was established creating a concentration calibration curve with a slope of 211 ohm/ln(pg mL-1), an R-squared value of 0.986 and a lower limit of detection of 742 fg mL-1. The specificity and cross-reactivity of the antibody with other hormones was tested through interferent and non-target experiments. Signal-to-noise ratio analysis verified that anti-17β-estradiol exhibited minimal chemical reactions with other hormones (SNR< 3) in non-target experiments. Additionally, there were minimal changes in the amount of signal collected during interferent testing, with albumin and follicle stimulating hormone having SNR values greater than 3. These results, along with the unique frequency response of the antibody-target binding reaction, allow for the possibility of using anti-17β-estradiol and β-estradiol for detecting multiple fertility biomarkers on a single sensor.
ContributorsSmith, Victoria Ann (Author) / LaBelle, Jeffrey (Thesis director) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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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
Acetaminophen, commonly found in Tylenol and other over the counter (OTC) pharmaceuticals, was electrochemically characterized on custom made, flexible, screen printed electrodes (SPEs) to serve as a model target pharmaceutical found in flowing water lines. Carbon, silver/silver chloride, and insulator paste inks were printed onto polyethylene naphthalateolyester (PEN) using custom

Acetaminophen, commonly found in Tylenol and other over the counter (OTC) pharmaceuticals, was electrochemically characterized on custom made, flexible, screen printed electrodes (SPEs) to serve as a model target pharmaceutical found in flowing water lines. Carbon, silver/silver chloride, and insulator paste inks were printed onto polyethylene naphthalateolyester (PEN) using custom made stencils for a 4x1 array of 3-electrode electrochemical cells. Cyclic voltammetry was performed to find the electrical potential corresponding to the greatest current response and the experiments were conducted using amperometric current-time mode (AMP*i-t). The physical limitations of SPEs as well as the detection limitations of the target, such as pH and temperature were tested. A concentration gradient of the target was fitted with a linear curve (R2 0.99), and a lower limit of detection of 14.5 μM. It was also found that both pH and temperature affect the current produced by acetaminophen at a fixed concentration, and that the sensors can detect target in a continuous flow. A flow apparatus consisting of an inlet and effluent pipe served as the flow model into which a rolled up flexible electrode array was inserted. The broader goal of this research is to develop a highly sensitive electrode array on flexible substrates which can detect multiple targets simultaneously. Acetaminophen was chosen due to its electro-active properties and its presence in most public water lines in the United States.
ContributorsMaxwell, Stephanie Ann (Author) / LaBelle, Jeffrey (Thesis director) / Allee, David (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Electrochemical sensors function by detecting electroactive species at the electrode surface of a screen printed sensor. As more force is applied, the concentration of electroactive species at the surface of the sensor increases and a larger current is measured. Thus, when all conditions including voltage are made constant, as in

Electrochemical sensors function by detecting electroactive species at the electrode surface of a screen printed sensor. As more force is applied, the concentration of electroactive species at the surface of the sensor increases and a larger current is measured. Thus, when all conditions including voltage are made constant, as in Amp i-t, a quantifiable current can be read and the force applied can be calculated. Two common electrochemical techniques in which current is measured, cyclic voltammetry(CV) and amperometric i-t(Amp i-t), were used. A compressible sensor capable of transducing a force and acquiring feedback was created.
ContributorsFeldman, Austin Marc (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Santello, Marco (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
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Description
Development of a rapid and label-free Electrochemical Impedance Spectroscopy (EIS) biosensor for Cardiovascular Disease (CVD) detection based on Inerluekin-18 (IL-18) sensitivity was proposed to fill the technology gap between rapid and portable CVD point-of-care diagnosis. IL-18 was chosen for this CVD biosensor due to its ability to detect plaque vulnerability

Development of a rapid and label-free Electrochemical Impedance Spectroscopy (EIS) biosensor for Cardiovascular Disease (CVD) detection based on Inerluekin-18 (IL-18) sensitivity was proposed to fill the technology gap between rapid and portable CVD point-of-care diagnosis. IL-18 was chosen for this CVD biosensor due to its ability to detect plaque vulnerability of the heart. Custom (hand) made sensors, which utilized a three electrode configuration with a gold disk working electrode, were created to run EIS using both IL-18 and anti-IL-18 molecules in both purified and blood solutions. The EIS results for IL-18 indicated the optimal detection frequency to be 371Hz. Blood interaction on the working electrode increased the dynamic range of impedance values for the biosensor. Future work includes Developing and testing prototypes of the biosensor along with determining if a Nafion based coating on the working electrode will reduce the dynamic range of impedance values caused by blood interference.
ContributorsJha, Amit (Author) / LaBelle, Jeffrey (Thesis director) / Mossman, Kenneth (Committee member) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / Department of Management (Contributor)
Created2013-05
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Description
The purpose of this research was to determine and evaluate glutamate oxidase's ability to detect levels of glutamate as part of a working sensor capable of quantifying and detecting stress within the body in the case of adverse neurological events such as traumatic brain injury. Using electrochemical impedance spectroscopy (EIS),

The purpose of this research was to determine and evaluate glutamate oxidase's ability to detect levels of glutamate as part of a working sensor capable of quantifying and detecting stress within the body in the case of adverse neurological events such as traumatic brain injury. Using electrochemical impedance spectroscopy (EIS), a linear dynamic range of glutamate was detected with a slope of 36.604 z/ohm/[pg/mL], a lower detection limit at 12.417 pg/mL, correlation of 0.97, and an optimal binding frequency of 117.20 Hz. After running through a frequency sweep the binding frequency was determined based on the highest consistent reproducibility and slope. The sensor was found to be specific against literature researched non-targets glucose, albumin, and epinephrine and working in dilutions of whole blood up to a concentration of 25%. With the implementation of Nafion, the sensor had a 250% improvement in signal and 155% improvement in correlation in 90% whole blood, illustrating the promise of a working blood sensor. Future work includes longitudinal studies and utilizing mesoporous carbon as the immobilization platform and incorporating this as part of a continuous, multiplexed blood sensor with glucose oxidase.
ContributorsLam, Alexandria Nicole (Author) / LaBelle, Jeffrey (Thesis director) / Ankeny, Casey (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description

Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo

Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo from the bodily environment, and reduction in systemic side effects. This experiment used a single emulsion technique to encapsulate L-tyrosine in PLGA microparticles and UV spectrophotometry to analyze the drug release over a period of one week. The release assay found that for the tested samples, the released amount is distinct initially, but is about the same after 4 days, and they generally follow the same normalized percent released pattern. The experiment could continue with testing more samples, test the same samples for a longer duration, and look into higher w/w concentrations such as 20% or 50%.

ContributorsSeo, Jinpyo (Author) / Vernon, Brent (Thesis director) / Pal, Amrita (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05