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DescriptionMy main goal for my thesis is in conjunction with the research I started in the summer of 2010 regarding the creation of a TBI continuous-time sensor. Such goals include: characterizing the proteins in sensing targets while immobilized, while free in solution, and while in free solution in the blood.
ContributorsHaselwood, Brittney (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Cook, Curtiss (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2011-12
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Description
Self-monitoring of blood glucose (SMBG) is the standard of care in diabetes management. Current technologies for SMBG are based upon enzymatic electrochemical (amperometric) sensing. To increase the sensitivity and specificity of current devices, a novel method of detecting glucose using electrochemical impedance spectroscopy (EIS) technology is explored. To test the

Self-monitoring of blood glucose (SMBG) is the standard of care in diabetes management. Current technologies for SMBG are based upon enzymatic electrochemical (amperometric) sensing. To increase the sensitivity and specificity of current devices, a novel method of detecting glucose using electrochemical impedance spectroscopy (EIS) technology is explored. To test the ability of EIS methods to detect glucose, the enzyme glucose oxidase (GOx) was fixed to gold electrodes through the means of a specific immobilization process. Once GOx was fixed to the gold electrode surface, a 5 mV sine wave sweeping frequencies from 100 kHz to 1 Hz was induced at a glucose range 0-500 mg/dL mixed with a ferricyanide redox mediator. Each frequency in the impedance sweep was analyzed for highest response and R-squared value. The frequency with both factors optimized is specific for the glucose-GOx binding interaction, and was determined to be 1.17 kHz in purified solutions. Four separate electrodes were constructed and date from each were averaged. The correlation between the impedance response and concentration at the low range of detection (0-100 mg/dL of gluose) was determined to be 3.19 ohm/ln (mg/dL) with an R-squared value of 0.86. Its associated lower limit of detection was found to be 41 mg/dL. The same frequency of 1.17 kHz was then verified in whole blood under the glucose range of 0-100 mg/dL while diluting the blood to observe effect. As the blood concentration increased, the response of the sensor decreased logarithmically. The maximized blood detection volume was determined to be 25% whole blood suggesting dilution, coatings, or filtration is required for future adaptation. The above data confirms that EIS offers a new method of glucose detection as an alternative technology for SMBG and offers improved detection at lower concentrations of glucose. The unique frequency response of individual markers allows for modulation of signals so that several markers could be measured with a single sensor. Future work includes assessment of other diabetes associated biomarkers that can be measured on a single sensor, integration testing and tuning of the biomarkers, impedance-time sensing development, and finally, testing on control subjects.
ContributorsAdamson, Teagan (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Cook, Curtiss (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
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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
Description
Volume depletion can lead to migraines, dizziness, and significant decreases in a subject's ability to physically perform. A major cause of volume depletion is dehydration, or loss in fluids due to an imbalance in fluid intake to fluid excretion. Because proper levels of hydration are necessary in order to maintain

Volume depletion can lead to migraines, dizziness, and significant decreases in a subject's ability to physically perform. A major cause of volume depletion is dehydration, or loss in fluids due to an imbalance in fluid intake to fluid excretion. Because proper levels of hydration are necessary in order to maintain both short and long term health, the ability to monitor hydration levels is growing in clinical demand. Although devices capable of monitoring hydration level exist, these devices are expensive, invasive, or inaccurate and do not offer a continuous mode of measurement. The ideal hydration monitor for consumer use needs to be characterized by its portability, affordability, and accuracy. Also, this device would need to be noninvasive and offer continuous hydration monitoring in order to accurately assess fluctuations in hydration data throughout a specified time period. One particular method for hydration monitoring that fits the majority of these criteria is known as bioelectric impedance analysis (BIA). Although current devices using BIA do not provide acceptable levels of accuracy, portability, or continuity in data collection, BIA could potentially be modified to fit many, if not all, desired customer specifications. The analysis presented here assesses the viability of using BIA as a new standard in hydration level measurement. The analysis uses data collected from 22 subjects using an existing device that employs BIA. A regression derived for estimating TBW based on the parameters of age, weight, height, sex, and impedance is presented. Using impedance data collected for each subject, a regression was also derived for estimating impedance based on the factors of age, weight, height, and sex. The derived regression was then used to calculate a new impedance value for each subject, and these new impedance values were used to estimate TBW. Through a paired-t test between the TBW values derived by using the direct measurements versus the calculated measurements of impedance, the two samples were found to be comparable. Considerations for BIA as a noninvasive measurement of hydration are discussed.
ContributorsTenorio, Jorge Antonio (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / W. P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
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Description
Currently, the management of diabetes mellitus (DM) involves the monitoring of only blood glucose using self-monitoring blood glucose devices (SMBGs) followed by taking interventional steps, if needed. To increase the amount of information that diabetics can have to base DM care decisions off of, the development of an insulin biosensor

Currently, the management of diabetes mellitus (DM) involves the monitoring of only blood glucose using self-monitoring blood glucose devices (SMBGs) followed by taking interventional steps, if needed. To increase the amount of information that diabetics can have to base DM care decisions off of, the development of an insulin biosensor is explored. Such a biosensor incorporates electrochemical impedance spectroscopy (EIS) to ensure an extremely sensitive platform. Additionally, anti-insulin antibody was immobilized onto the surface of a gold disk working electrode to ensure a highly specific sensing platform as well. EIS measurements were completed with a 5mV sine wave that was swept through the frequency spectrum of 100 kHz to 1 Hz on concentrations of insulin ranging from 0 pM to 100 μM. The frequency at which the interaction between insulin and its antibody was optimized was determined by finding out at which frequency the R2 and slope of the impedance-concentration plot were best. This frequency, otherwise known as the optimal binding frequency, was determined to be 459 Hz. Three separate electrodes were developed and the impedance data for each concentration measured at 459 Hz was averaged and plotted against the LOG (pM insulin) to construct the calibration curve. The response was calculated to be 263.64 ohms/LOG(pM insulin) with an R2 value of 0.89. Additionally, the average RSD was determined to be 19.24% and the LLD was calculated to be 8.47 pM, which is well below the physiological normal range. These results highlight the potential success of developing commercial point-of-care insulin biosensors or multi-marker devices operating with integrated insulin detection.
ContributorsDecke, Zachary William (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Cook, Curtiss (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
The action/adventure game Grad School: HGH is the final, extended version of a BME Prototyping class project in which the goal was to produce a zombie-themed game that teaches biomedical engineering concepts. The gameplay provides fast paced, exciting, and mildly addicting rooms that the player must battle and survive through,

The action/adventure game Grad School: HGH is the final, extended version of a BME Prototyping class project in which the goal was to produce a zombie-themed game that teaches biomedical engineering concepts. The gameplay provides fast paced, exciting, and mildly addicting rooms that the player must battle and survive through, followed by an engineering puzzle that must be solved in order to advance to the next room. The objective of this project was to introduce the core concepts of BME to prospective students, rather than attempt to teach an entire BME curriculum. Based on user testing at various phases in the project, we concluded that the gameplay was engaging enough to keep most users' interest through the educational puzzles, and the potential for expanding this project to reach an even greater audience is vast.
ContributorsNitescu, George (Co-author) / Medawar, Alexandre (Co-author) / Spano, Mark (Thesis director) / LaBelle, Jeffrey (Committee member) / Guiang, Kristoffer (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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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