A. James Clark School of Engineering
Permanent URI for this communityhttp://hdl.handle.net/1903/1654
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
Browse
9 results
Search Results
Item Miniaturized Capsule System Toward Real-Time Electrochemical Detection of H2S in the Gastrointestinal Tract(Wiley, 2023-11-20) Stine, Justin M.; Ruland, Katie L.; Beardslee, Luke A.; Levy, Joshua A.; Abianeh, Hossein; Botasini, Santiago; Pasricha, Pankaj J.; Ghodssi, RezaHydrogen sulfide (H2S) is a gaseous inflammatory mediator and important signaling molecule for maintaining gastrointestinal (GI) homeostasis. Excess intraluminal H2S in the GI tract has been implicated in inflammatory bowel disease and neurodegenerative disorders; however, the role of H2S in disease pathogenesis and progression is unclear. Herein, an electrochemical gas-sensing ingestible capsule is developed to enable real-time, wireless amperometric measurement of H2S in GI conditions. A gold (Au) three-electrode sensor is modified with a Nafion solid-polymer electrolyte (Nafion-Au) to enhance selectivity toward H2S in humid environments. The Nafion-Au sensor-integrated capsule shows a linear current response in H2S concentration ranging from 0.21 to 4.5 ppm (R2 = 0.954) with a normalized sensitivity of 12.4% ppm−1 when evaluated in a benchtop setting. The sensor proves highly selective toward H2S in the presence of known interferent gases, such as hydrogen (H2), with a selectivity ratio of H2S:H2 = 1340, as well as toward methane (CH4) and carbon dioxide (CO2). The packaged capsule demonstrates reliable wireless communication through abdominal tissue analogues, comparable to GI dielectric properties. Also, an assessment of sensor drift and threshold-based notification is investigated, showing potential for in vivo application. Thus, the developed H2S capsule platform provides an analytical tool to uncover the complex biology-modulating effects of intraluminal H2S.Item Chitosan to Connect Biology to Electronics: Fabricating the Bio-Device Interface and Communicating Across This Interface(MDPI, 2014-12-24) Kim, Eunkyoung; Xiong, Yuan; Cheng, Yi; Wu, Hsuan-Chen; Liu, Yi; Morrow, Brian H.; Ben-Yoav, Hadar; Ghodssi, Reza; Rubloff, Gary W.; Shen, Jana; Bentley, William E.; Shi, Xiaowen; Payne, Gregory F.Individually, advances in microelectronics and biology transformed the way we live our lives. However, there remain few examples in which biology and electronics have been interfaced to create synergistic capabilities. We believe there are two major challenges to the integration of biological components into microelectronic systems: (i) assembly of the biological components at an electrode address, and (ii) communication between the assembled biological components and the underlying electrode. Chitosan possesses a unique combination of properties to meet these challenges and serve as an effective bio-device interface material. For assembly, chitosan’s pH-responsive film-forming properties allow it to “recognize” electrode-imposed signals and respond by self-assembling as a stable hydrogel film through a cathodic electrodeposition mechanism. A separate anodic electrodeposition mechanism was recently reported and this also allows chitosan hydrogel films to be assembled at an electrode address. Protein-based biofunctionality can be conferred to electrodeposited films through a variety of physical, chemical and biological methods. For communication, we are investigating redox-active catechol-modified chitosan films as an interface to bridge redox-based communication between biology and an electrode. Despite significant progress over the last decade, many questions still remain which warrants even deeper study of chitosan’s structure, properties, and functions.Item The Binding Effect of Proteins on Medications and Its Impact on Electrochemical Sensing: Antipsychotic Clozapine as a Case Study(MDPI, 2017-08-01) Banis, George E.; Winkler, Thomas; Barton, Patricia; Chocron, Sheryl E.; Kim, Eunkyoung; Kelly, Deanna L.; Payne, Gregory F.; Ben-Yoav, Hadar; Ghodssi, RezaClozapine (CLZ), a dibenzodiazepine, is demonstrated as the optimal antipsychotic for patients suffering from treatment-resistant schizophrenia. Like many other drugs, understanding the concentration of CLZ in a patient’s blood is critical for managing the patients’ symptoms, side effects, and overall treatment efficacy. To that end, various electrochemical techniques have been adapted due to their capabilities in concentration-dependent sensing. An open question associated with electrochemical CLZ monitoring is whether drug–protein complexes (i.e., CLZ bound to native blood proteins, such as serum albumin (SA) or alpha-1 acid-glycoprotein (AAG)) contribute to electrochemical redox signals. Here, we investigate CLZ-sensing performance using fundamental electrochemical methods with respect to the impact of protein binding. Specifically, we test the activity of bound and free fractions of a mixture of CLZ and either bovine SA or human AAG. Results suggest that bound complexes do not significantly contribute to the electrochemical signal for mixtures of CLZ with AAG or SA. Moreover, the fraction of CLZ bound to protein is relatively constant at 31% (AAG) and 73% (SA) in isolation with varying concentrations of CLZ. Thus, electrochemical sensing can enable direct monitoring of only the unbound CLZ, previously only accessible via equilibrium dialysis. The methods utilized in this work offer potential as a blueprint in developing electrochemical sensors for application to other redox-active medications with high protein binding more generally. This demonstrates that electrochemical sensing can be a new tool in accessing information not easily available previously, useful toward optimizing treatment regimens.Item Gelatin-Enabled Microsensor for Pancreatic Trypsin Sensing(MDPI, 2018-01-31) Banis, George; Beardslee, Luke A.; Ghodssi, RezaDigestive health is critically dependent on the secretion of enzymes from the exocrine pancreas to the duodenum via the pancreatic duct. Specifically, pancreatic trypsin is a major protease responsible for breaking down proteins for absorption in the small intestine. Gelatin-based hydrogels, deposited in the form of thin films, have been studied as potential sensor substrates that hydrolyze in the presence of trypsin. In this work, we (1) investigate gelatin as a sensing material; (2) develop a fabrication strategy for coating sensor surfaces; and (3) implement a miniaturized impedance platform for measuring activity levels of pancreatic trypsin. Using impedance spectroscopy, we evaluate gelatin’s specificity and rate of degradation when exposed to a combination of pancreatic enzymes in neutral solution representative of the macromolecular heterogeneity present in the duodenal environment. Our findings suggest gelatin’s preferential degradation to trypsin compared to enzymes such as lipase and amylase. We further observe their interference with trypsin behavior in equivalent concentrations, reducing film digestion by as much as 83% and 77%, respectively. We achieve film patterns in thicknesses ranging from 300–700 nm, which we coat over interdigitated finger electrode sensors. Finally, we test our sensors over several concentrations to emulate the range of pancreatic secretions. Ultimately, our microsensor will serve as the foundation for developing in situ sensors toward diagnosing pancreatic pathologies.Item Adsorption Kinetic Model Predicts and Improves Reliability of Electrochemical Serotonin Detection(MDPI, 2023-01-09) Chapin, Ashley Augustiny; Han, Jinjing; Ghodssi, RezaSerotonin (5-HT) is a neurotransmitter involved in many biophysiological processes in the brain and in the gastrointestinal tract. Electrochemical methods are commonly used to quantify 5-HT, but their reliability may suffer due to the time-dependent nature of adsorption-limited 5-HT detection, as well as electrode fouling over repeated measurements. Mathematical characterization and modeling of adsorption-based electrochemical signal generation would improve reliability of 5-HT measurement. Here, a model was developed to track 5-HT electrode adsorption and resulting current output by combining Langmuir adsorption kinetic equations and adsorption-limited electrochemical equations. 5-HT adsorption binding parameters were experimentally determined at a carbon-nanotube coated Au electrode: KD = 7 × 10−7 M, kon = 130 M−1 s−1, koff = 9.1 × 10−5 s−1. A computational model of 5-HT adsorption was then constructed, which could effectively predict 5-HT fouling over 50 measurements (R2 = 0.9947), as well as predict electrode responses over varying concentrations and measurement times. The model aided in optimizing the measurement of 5-HT secreted from a model enterochromaffin cell line—RIN14B—minimizing measurement time. The presented model simplified and improved the characterization of 5-HT detection at the selected electrode. This could be applied to many other adsorption-limited electrochemical analytes and electrode types, contributing to the improvement of application-specific modeling and optimization processes.Item Thermomechanical Soft Actuator for Targeted Delivery of Anchoring Drug Deposits to the GI Tract(Wiley, 2022-12-04) Levy, Joshua A.; Straker, Michael A.; Stine, Justin M.; Beardslee, Luke A.; Borbash, Vivian; Ghodssi, RezaCurrent systemic therapies for inflammatory gastrointestinal (GI) disorders are unable to locally target lesions and have substantial systemic side effects. Here, a compact mesoscale spring actuator capable of delivering an anchoring drug deposit to point locations in the GI tract is demonstrated. The mechanism demonstrated here is intended to complement existing ingestible capsule-based sensing and communication technologies, enabling treatment based on criteria such as detected GI biomarkers or external commands. The 3D-printed actuator has shown on command deployment in 14.1 ± 3.0 s, and a spring constant of 25.4 ± 1.4 mN mm−1, sufficient to insert a spiny microneedle anchoring drug deposit (SMAD) into GI tissue. The complementary SMAD showed a 22-fold increase in anchoring force over traditional molded microneedles, enabling reliable removal from the actuator and robust prolonged tissue attachment. The SMAD also showed comparable drug release characteristics (R2 = 0.9773) to penetrating molded microneedles in agarose phantom tissue with a drug spread radius of 25 mm in 168 h. The demonstrated system has the potential to enable on command delivery and anchoring of drug-loaded deposits to the GI mucosa for sustained treatment of GI inflammation while mitigating side effects and enabling new options for treatment.Item Gelatin-Enabled Microsensor for Pancreatic Trypsin Sensing(MDPI, 2018-01-31) Banis, George; Beardslee, Luke A.; Ghodssi, RezaDigestive health is critically dependent on the secretion of enzymes from the exocrine pancreas to the duodenum via the pancreatic duct. Specifically, pancreatic trypsin is a major protease responsible for breaking down proteins for absorption in the small intestine. Gelatin-based hydrogels, deposited in the form of thin films, have been studied as potential sensor substrates that hydrolyze in the presence of trypsin. In this work, we (1) investigate gelatin as a sensing material; (2) develop a fabrication strategy for coating sensor surfaces; and (3) implement a miniaturized impedance platform for measuring activity levels of pancreatic trypsin. Using impedance spectroscopy, we evaluate gelatin’s specificity and rate of degradation when exposed to a combination of pancreatic enzymes in neutral solution representative of the macromolecular heterogeneity present in the duodenal environment. Our findings suggest gelatin’s preferential degradation to trypsin compared to enzymes such as lipase and amylase. We further observe their interference with trypsin behavior in equivalent concentrations, reducing film digestion by as much as 83% and 77%, respectively. We achieve film patterns in thicknesses ranging from 300–700 nm, which we coat over interdigitated finger electrode sensors. Finally, we test our sensors over several concentrations to emulate the range of pancreatic secretions. Ultimately, our microsensor will serve as the foundation for developing in situ sensors toward diagnosing pancreatic pathologies.Item The Binding Effect of Proteins on Medications and Its Impact on Electrochemical Sensing: Antipsychotic Clozapine as a Case Study(Multidisciplinary Digital Publishing Institute (MDPI), 2017-08-01) Banis, George E.; Winkler, Thomas; Barton, Patricia; Chocron, Sheryl E.; Kim, Eunkyoung; Kelly, Deanna L.; Payne, Gregory F.; Ben-Yoav, Hadar; Ghodssi, RezaClozapine (CLZ), a dibenzodiazepine, is demonstrated as the optimal antipsychotic for patients suffering from treatment-resistant schizophrenia. Like many other drugs, understanding the concentration of CLZ in a patient’s blood is critical for managing the patients’ symptoms, side effects, and overall treatment efficacy. To that end, various electrochemical techniques have been adapted due to their capabilities in concentration-dependent sensing. An open question associated with electrochemical CLZ monitoring is whether drug–protein complexes (i.e., CLZ bound to native blood proteins, such as serum albumin (SA) or alpha-1 acid-glycoprotein (AAG)) contribute to electrochemical redox signals. Here, we investigate CLZ-sensing performance using fundamental electrochemical methods with respect to the impact of protein binding. Specifically, we test the activity of bound and free fractions of a mixture of CLZ and either bovine SA or human AAG. Results suggest that bound complexes do not significantly contribute to the electrochemical signal for mixtures of CLZ with AAG or SA. Moreover, the fraction of CLZ bound to protein is relatively constant at 31% (AAG) and 73% (SA) in isolation with varying concentrations of CLZ. Thus, electrochemical sensing can enable direct monitoring of only the unbound CLZ, previously only accessible via equilibrium dialysis. The methods utilized in this work offer potential as a blueprint in developing electrochemical sensors for application to other redox-active medications with high protein binding more generally. This demonstrates that electrochemical sensing can be a new tool in accessing information not easily available previously, useful toward optimizing treatment regimens.Item Effect of electrical energy on the efficacy of biofilm treatment using the bioelectric effect(Nature Publishing Group, 2015-09-23) Kim, Young Wook; Subramanian, Sowmya; Gerasopoulos, Konstantinos; Ben-Yoav, Hadar; Wu, Hsuan-Chen; Quan, David; Carter, Karen; Meyer, Mariana T.; Bentley, William E.; Ghodssi, RezaBACKGROUND/OBJECTIVES: The use of electric fields in combination with small doses of antibiotics for enhanced treatment of biofilms is termed the ‘bioelectric effect’ (BE). Different mechanisms of action for the AC and DC fields have been reported in the literature over the last two decades. In this work, we conduct the first study on the correlation between the electrical energy and the treatment efficacy of the bioelectric effect on Escherichia coli K-12 W3110 biofilms. METHODS: A thorough study was performed through the application of alternating (AC), direct (DC) and superimposed (SP) potentials of different amplitudes on mature E. coli biofilms. The electric fields were applied in combination with the antibiotic gentamicin (10 μg/ml) over a course of 24 h, after the biofilms had matured for 24 h. The biofilms were analysed using the crystal violet assay, the colony-forming unit method and fluorescence microscopy. RESULTS: Results show that there is no statistical difference in treatment efficacy between the DC-, AC- and SP-based BE treatment of equivalent energies (analysis of variance (ANOVA) P > 0.05) for voltages < 1 V. We also demonstrate that the efficacy of the BE treatment as measured by the crystal violet staining method and colony-forming unit assay is proportional to the electrical energy applied (ANOVA P < 0.05). We further verify that the treatment efficacy varies linearly with the energy of the BE treatment (r2 = 0.984). Our results thus suggest that the energy of the electrical signal is the primary factor in determining the efficacy of the BE treatment, at potentials less than the media electrolysis voltage. CONCLUSIONS: Our results demonstrate that the energy of the electrical signal, and not the type of electrical signal (AC or DC or SP), is the key to determine the efficacy of the BE treatment. We anticipate that this observation will pave the way for further understanding of the mechanism of action of the BE treatment method and may open new doors to the use of electric fields in the treatment of bacterial biofilms.