Matching Items (53)

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Utilization of Electrochemical Impedance Spectroscopy for the Detection of QSOX1 and CEA

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

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.

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2017-05

Towards the Development of a Multimarker Platform for Point-of-Care Monitoring of Solid Organ Transplant Patient Health through Impedance-Time Testing of Tacrolimus Cystatin-C, and IL-12

Description

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

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.

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2017-05

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Proof of Concept of Pseudo-Continuous Monitoring of L-Lactate Levels Using Electrochemical Impedance Spectroscopy

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

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.

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2017-05

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The Development of a Comfortable Myoelectric Prosthetic Socket \u2014 Fishbone

Description

This paper proposes a new socket design to complement Project Fishbone, a design project focused on creating a lightweight transradial prosthetic device. The socket has a simple concept of introducing perforations on the surface of the socket using cost effective,

This paper proposes a new socket design to complement Project Fishbone, a design project focused on creating a lightweight transradial prosthetic device. The socket has a simple concept of introducing perforations on the surface of the socket using cost effective, and rapid manufacturing methods such as vacuum thermoforming and drilling. The perforations on the socket allows for greater air ventilation to the prosthetic user's residual skin thus reducing the temperature within the socket. There were nine primary design iterations that were tested: 0.125, 0,187, 0.25-inch-thick designs, and 3/16, 15/64, 17/64-inch perforation sizes, and 12, 18 and 24 count of perforations. Initial test was done using the sockets of different thickness without any perforations to check for uniformity in design and manufacturing method using a regression test. It was found that an increase in thickness directly related to an increase in temperature cooling time. The temperature cooling test was run using a three-factor DOE method and no clear interaction between the factors was observed, thus the Kruskal-Wallis statistical test along with the post hoc Mann-Whitney test to check for significance among the factors as well as significance of groups within the factors. Statistical significance (p<0.05) was found in the socket thickness and size of perforations. Additionally, significance (p<0.02) was found in the 0.125 and 0.187-inch thickness and the 3/16-inch size perforations. Based on the significance between each group, the best combination for increased cooling time reduction was thus found to be with the 0.125-inch thick HDPE sheet and 3/16-inch sized perforation while the number of perforations did not make much difference. These results proved the concept of this new socket design that could be implemented into existing upper limb prosthetic systems.

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2017-05

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Classification and Application of Electroactive Poly-Amidoamine Polymer (EPOP) for Use in Glucose Sensors

Description

Research concerning increased sensitivity and accurate glucose sensors have been on the forefront of diabetes mellitus. In this study, Electroactive Poly-Amidoamine Polymer (EPOP) was studied to determine if it can be used as a biocompatible electrode, with known redox mediators

Research concerning increased sensitivity and accurate glucose sensors have been on the forefront of diabetes mellitus. In this study, Electroactive Poly-Amidoamine Polymer (EPOP) was studied to determine if it can be used as a biocompatible electrode, with known redox mediators to determine if it can transfer its own electrons or amplify signal, and if signal is amplified when using an Ag/AgCl working electrode. From the results, it was determined that EPOP is neither a redox mediator, since it cannot transfer its own electrons, nor an electron mediator, since it does not amplify measured current at a specific voltage. Rather, it behaves as an electron sink capacitor with inconsistent behavior when Ag/AgCl is used as the working electrode with the redox mediator alone or with the redox mediator using in combination with glucose oxidase (GOx) and glucose. This was validated using AC-Impedance which gave a -3.3999 slope for isolated 0.05 g/mL EPOP in solution and R2 value of 0.992 displaying it had more capacitor-like behavior compared to resistor-like behavior. For this reason, EPOP was infused into a carbon screen-printed electrode by adding it dissolved and undissolved at two levels into carbon ink. The effectiveness of this electrode was tested using a potentiostatic CV. For the 0.1 g/mL EPOP dissolved in carbon ink, the reduction voltage peak (0.18 V) was found to be slightly higher than a GDE (0.14 V); however, the measured current was found to be 1.57 times the amplitude of a GDE. When 0.05 g/mL EPOP in PBS dissolved in graphite ink was used to detect glucose as the working electrode, there was increased signal amplification, and therefore, increased sensitivity to glucose when using EPOP infused electrodes. This offers promising results for disposable glucose sensors.

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2017-05

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Characterization and Optimization of Ion-Sensitive Field Effect Transistors for Rapid Personalized Diagnostics

Description

The growth of the medical diagnostic industry in the past several decades has largely been due to the creation and iterative optimization of bio sensors. Recent pushes towards value added as well as preventative health care has made point of

The growth of the medical diagnostic industry in the past several decades has largely been due to the creation and iterative optimization of bio sensors. Recent pushes towards value added as well as preventative health care has made point of care devices more attractive to health care providers. Rapid detection for diseases and cancers is done with a bio sensor, which a broad term used to describe an instrument which uses a bio chemical reaction to detect a chemical compound with the use of a bio recognition event in addition to a signal detection event. The bio sensors which are presented in this work are known as ion-sensitive field effects transistors (ISFETs) and are similar in function to a metal oxide field effect transistor (MOSFET). These ISFETs can be used to sense pH or the concentration of protons on the surface of the gate channel. These ISFETs can be used for certain bio recognition events and this work presents the application of these transistors for the quantification of tumor cell proliferation. This includes the development of a signal processing and acquisition system for the long term assessment of cellular metabolism and optimizing the system for use in an incubator. This thesis presents work done towards the optimization and implementation of complementary metal\u2014oxide\u2014semiconductor (CMOS) ISFETs as well as remote gate ISFETs for the continuous assessment of tumor cell extracellular pH. The work addresses the challenges faced with the fabrication and optimization of these sensors, which includes the mitigation of current drift with the use of pulse width modulation in addition to issues encountered with fabrication of electrodes on a quartz substrate. This work culminates in the testing of an autonomous system with mammary tumor cells as well as the assessment of cell viability in an incubator over extended periods. Future applications of this work include the creation of a remote gate ISFET array for multiplexed detection as well as the implementation of ISFETs for bio marker detection via an immunoassay.

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2017-05

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Mechanical Design Optimization of Intraoperative Spinal Load Sensing during Scoliosis Correction Surgery

Description

Technologies used in corrective scoliosis surgery do not provide accurate, validated measurements of applied loading on the spine. Proposing a solution to optimize intra-operative load sensing to enhance surgical outcomes, mechanical factors of a capacitive load sensor are examined. Using

Technologies used in corrective scoliosis surgery do not provide accurate, validated measurements of applied loading on the spine. Proposing a solution to optimize intra-operative load sensing to enhance surgical outcomes, mechanical factors of a capacitive load sensor are examined. Using ASTM D3574-17, experimental methods were performed to verify material homogeneity and validity, to identify critical factors in maximizing compressive strength, and to understand preliminary fatigue behavior for reliability measures. In leveraging the Design of Experiment (DOE) methodology to decrease device variability, the mechanical factors explored were: sensor thickness, diameter ratio of conductive foam, density, and surface hardness. Multiple iterations DOEs identified high thickness and low diameter ratios as significant factors which increase the output response of compressive strength. After identifying the optimal factor combination for the sensor it was found that the maximum experimental load range was 15.57N-16.9lbf. Fatigue testing was then performed on the highest performing factor combination group from the compression results. From the two rounds that were tested on sensor specimen, no significant difference was found between the two groups' rates of changes in thickness per compression. Each round of foam testing resulted in similar thickness values, which suggests that the sensor has potential to perform consistently during a 6-8 hour surgery if a material with improved elasticity and mechanical strength is used. Thus, the experimental procedures fulfill proof-of-concept tests to indicate feasibility of compressive strength and reliability of the sensor's mechanical features. Future experimentations will involve using a different dielectric material in place of the foam, such as a conductive thermoset or thermoplastic elastomer. Additional levels for each factor will be test to test the behavior of the material to yield a higher compressive strength and certainty of reliability. Overall, this study was useful in identifying significant factors for achieving compressive strength, while also providing evidence of the device's potential for reliability during scoliosis surgeries.

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2018-05

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An Investigation into the Causes of Insulin Aggregation

Description

Insulin is an essential peptide hormone that aides in the metabolism of glucose by allowing the cells to uptake glucose. Exogenous insulin is often prescribed to patients in order to help manage their diabetes. Recent research has indicated that prescription

Insulin is an essential peptide hormone that aides in the metabolism of glucose by allowing the cells to uptake glucose. Exogenous insulin is often prescribed to patients in order to help manage their diabetes. Recent research has indicated that prescription insulin is not at the labeled concentration when the prescription is filled by the patient. This decrease in concentration from when the insulin is manufactured to when it reaches the pharmacy is likely due to the insulin denaturing and aggregating. Dynamic light scattering is a useful and accurate method to determine the hydrodynamic radius of a solute and can be used to measure the hydrodynamic radius of insulin which will thus determine the aggregation of the sample since the more aggregated it is, the larger the hydrodynamic radius will be. By testing the effect of pH, concentration, temperature, and time on insulin samples, the optimal storage conditions can be determined in order to ensure researchers and patients are not using aggregated insulin. No conclusive relationship was found between any variable and sample diameter, but several trends were identified. Temperature, pH, and time in solution are all factors that could impact the aggregation, and therefore activity, of insulin. However, concentration did not show any trend regarding aggregation. Determining the relationships between these variables could allow for the identification of ideal storage conditions for researchers. Additionally, it can be used to identify shortcomings in the insulin supply chain.

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2018-05

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Development of Electrochemical Methods to Enzymatically Detect Traumatic Brain Injury Biomarkers

Description

As awareness of traumatic brain injury (TBI) increases, the need to detect mild forms and distinguish between the different severities of TBI becomes more apparent. The goal of this work is to develop a point-of-care sensor to detect whole blood

As awareness of traumatic brain injury (TBI) increases, the need to detect mild forms and distinguish between the different severities of TBI becomes more apparent. The goal of this work is to develop a point-of-care sensor to detect whole blood biomarkers for rapid and sensitive diagnosis of TBI severity. Presented herein is the enzymatic detection of norepinephrine through the use of immobilization chemistry and impedance techniques. Sustained elevation of norepinephrine concentrations in the blood has been correlated to negative long-term outcomes in TBI cases, often resulting in permanent cognitive or physical deficits.

Novel analysis techniques have been used to identify an optimal binding frequency (371.1 Hz) of norepinephrine to the immobilized enzyme on a gold disk electrode. This form of analysis yielded a logarithmic fit characterized by exceptional responsivity (20.89 Ω/pgmL-1), reproducibility (R2 = 0.96), and lower limit of detection (98 pg/mL) first in purified samples, then in rabbit whole blood solutions. Once the optimal binding frequency was determined, the preliminary use of an impedance-time technique was attempted in this work. This technique more closely resembles the amperometric detection method used in commercial self-monitoring blood glucose meters, allowing for continuous or instantaneous measurement of blood borne biomarkers without compromising sensitivity. Future directions include exploration of simultaneous multi-marker detection with the impedance-time technique and experimentation with novel mesoporous materials to filter large blood components.

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Date Created
2015-05-15

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Method for Fabrication and Verification of Conjugated Nanoparticle-Antibody Tuning Elements for Multiplexed Electrochemical Biosensors

Description

There is a critical need for more accurate, highly sensitive and specific assay for disease diagnosis and management. A novel, multiplexed, single sensor using rapid and label free electrochemical impedance spectroscopy tuning method has been developed. The key challenges while

There is a critical need for more accurate, highly sensitive and specific assay for disease diagnosis and management. A novel, multiplexed, single sensor using rapid and label free electrochemical impedance spectroscopy tuning method has been developed. The key challenges while monitoring multiple targets is frequency overlap. Here we describe the methods to circumvent the overlap, tune by use of nanopartide (NP) and discuss the various fabrication and characterization methods to develop this technique. First sensors were fabricated using printed circuit board (PCB) technology and nickel and gold layers were electrodeposited onto the PCB sensors. An off-chip conjugation of gold NP's to molecular recognition elements (with verification technique) is described as well. A standard covalent immobilization of the molecular recognition elements is also discussed with quality control techniques. Finally use and verification of sensitivity and specificity is also presented. By use of gold NP's of various sizes, we have demonstrated the possibility and shown little loss of sensitivity and specificity in the molecular recognition of inflammatory markers as "model" targets for our tuning system. By selection of other sized NP's or NP's of various materials, the tuning effect can be further exploited. The novel platform technology developed could be utilized in critical care, clinical management and at home health and disease management.

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2013-09-09