Browsing by Author "Sirsi, Shashank"
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Item Demonstration of POC Biosensor Toward Clinical Translation for Patient Bed-side Monitoring(December 2021) Tanak, Ambalika Sanjeev; Prasad, Shalini; Walker, Amy V.; Muthukumar, Sriram; Sirsi, Shashank; Ardestani Khoubrouy, SoudehThe research presented in this dissertation focuses on developing and characterizing a multiplexed affinity based electrochemical biosensing device toward clinical translation. The goal of this work is to establish a portable POC device for early disease detection across diverse healthcare applications using low sample volume, rapid response time and usability amongst minimally trained individual relying on ASSURED (Affordable, Sensitive, Specific, User friendly, rapid, and Robust, Equipment free and Deliverable to end users) criteria. Primarily, we designed a robust, non-faradaic electrochemical affinity biosensing platform for the rapid assessment of parathyroid hormone (PTH) as a single biosensing system. Unique high density semiconducting nanostructured arrays on a flexible sensing surface were used to create the analytical nanobiosensor. The surface modification technique was specifically designed to improve the interaction of the nanostructure–biological interface to capture the desired PTH level in HS and plasma. This was followed by evaluating the analytical performance of the developed biosensor with clinical rigor. The assay validation results were compared with laboratory standard as reference with results that demonstrated comparable performance with higher accuracy. Next, the scope of the biosensor was expanded to solve a clinically challenging problem of detecting host immune markers for life-threatening sepsis infection. Herein, we demonstrate a first-of-a-kind multiplexed POC biosensing device that simultaneously detects a panel of eight key immune response cytokine biomarkers in sample volume equivalent to two drops of plasma and whole blood within 5 minutes without sample dilution. Moreover, this work focuses on validating the developed biosensing device with LUMINEX standard reference method for clinical translation using nearly 200 patient samples. The DeTecT (Direct Electrochemical Technique Targeting) Sepsis biosensing device is surface engineered with specific capture probes that utilizes EIS to measure the capacitive impedance change reflecting binding interactions between the capture probe and target biomarker enabling multiplexed detection. Specificity of the biosensor was validated using cross-reactive studies, which displayed insignificant interference from non-specific biomarkers. The biosensor also displays stable and repeatable performance. The novelty presented in this research combines the effectiveness of choosing specific host immune response biomarkers for detection of sepsis combined with unique surface modification strategy coupled with EIS technique to enable efficient clinical decision-making process. This unique sensor technology would allow medical practitioners to facilitate targeted interventions for septic patients as a rapid prognostic approach, preventing complications arriving from sepsis.Item Developing a Flexible, Affinity-based, Electrochemical Sensing Platform Towards Multiplexed Detection of Apocrine and Eccrine Sweat Based Biomarkers; SLOCK: Sensor for Circadian Clock(December 2021) Upasham, Sayali; Prasad, Shalini; Gupta, Gopal; Rodrigues, Danieli; Polk, Todd; Sirsi, ShashankChronobiology is defined as the temporal fluctuations occurring in the human physiology due to the circadian cycle. These fluctuations are good indicators of the functioning of the HypothalamicPituitary-Adrenal axis (HPA axis) and can be tracked by using biomarkers: Cortisol and Dehydroepiandrosteron (DHEA). Low volume tracking systems are beneficial for patients exposed to chronic stress, patients suffering from endocrine conditions manifested by circadian disruption and act as a lifestyle monitoring tool. An estimate of 50-70 million Americans suffer from chronic sleep disorders (NHLBI, 2003) which hinders routine functioning and has deleterious health implications including elevated cortisol levels, increased risk of hypertension, diabetes, depression, cardiac conditions, and stroke. Currently available technologies for monitoring the circadian rhythm (e.g., Polysomnography (Ambulatory monitoring of nocturnal sleep) or Actigraphy (Multiday ambulatory assessment)) do not provide an accurate estimation of the extent of circadian disruption, as they are superficial. Biomarker assays are the diagnostic gold standard techniques used for the diagnosis of circadian dysregulation caused by adrenal disorders. These assays usually rely on the use of blood or serum and take about 3-4 hours for the test results which proves to be an ineffective solution, from the point of view of developing a circadian profile for the user. Adrenal steroids like cortisol and DHEA are expressed in sweat in the nanogram range and can be used as biomarkers to facilitate self-monitoring. SLOCK is a sweat based chronobiology tracking system that works on the principles of electrochemically transduced affinity-based systems. The sensor can detect cortisol and DHEA in the physiologically relevant ranges i.e., 8-200 ng/ml and 2-131 ng/ml respectively. The sensor was also tested through human subject-based studies and is able to capture rise and fall in biomarker levels on-body. In addition to this, the use of serpentine interdigitated electrodes provides mechanical stability when exposed to oscillations caused due to a wearable form factor. Based on the cross-reactivity studies, the response for target biomarkers is highly specific to the biomarker of interest. Towards the last part of this work, the SLOCK platform was tuned for detection of a protein biomarker, interleukin-31 (IL-31) for the purpose of creating a chronic disease diagnosis and management platform. The benchmarking for this was carried out by modelling it for detection of atopic dermatitis related flares. The platform is able to sensitively detect IL-31 over the dynamic range of 50-1000 pg/mL. The platform was successfully coupled with portable electronics and was able to record biomarker fluctuations on-body through human subject-based testing. The SLOCK platforms offers highly sensitive, non-invasive monitoring of circadian related or chronic disorders in a point-of-need setting.Item Formulation and Development of UV Activated Polymer Microbubbles as Ultrasound Contrast Agents for Imaging and Drug Delivery(2020-04-30) Pawar, Muskan; Sirsi, ShashankMicrobubbles, as contrast agents and drug carriers, have been widely used for the ranostic applications with ultrasound technology over the past three decades. Research in microbubbles has undergone numerous improvements from a compositional perspective as researchers aim for enhanced targeted drug delivery. Microbubbles shells, which typically encapsulate a gaseous core, are conventionally classified into three type’s proteins, lipids, and polymers. Polylactic Acid (PLA) polymers are FDA approved and have proven to be one of the best biomaterials for fabricating drug delivery vehicles owing to its stability when introduced in vivo. When PLA is used to fabricate microbubbles, drugs of interest can be encapsulated into the polymer shells and can be released at the site with the application of ultrasound to achieve targeted drug delivery. But two limitations encountered with this microbubbles are a lack of controlled drug release upon triggering and elasticity of polymer shell in an ultrasound field. This research focuses on the development of novel Ultraviolet (UV) sensitive shape changeable polymer microbubbles to improve polymer shell properties. Fabrication of these microbubbles was done by modifying a double emulsification method. A UV sensitive shape changeable polymer, Azobenzene, has been used along with PLA to address the elasticity issue. This blend of two polymers present in the microbubble shell has resulted in structural changes like pores, cracks, and golf-ball like appearances, in response to UV light. These structural changes are indicative of a change in flexibility of otherwise stiff PLA microbubble shell. Scanning Electron Microscopy images show a clear structural difference in UV exposed microbubbles. UV-Vis Spectroscopy results show the optical properties of these microbubbles and confirm the activation of UV sensitive polymer present on the microbubble shell. The reported differences confirm the change in structure and lay the foundation for future work where acoustic properties of this novel polymer microbubbles tested for elasticity followed by testing of drug encapsulation and drug release profile for controlled delivery and cell toxicity testing for biocompatibility of the azobenzene.Item Investigation of Sweat Biomarkers for Real-time Reporting of Infection and Inflammation Using Wearable Sweat Sensor(December 2021) Jagannath, Badrinath; Prasad, Shalini; Bereg, Sergey; Muthukumar, Sriram; Sirsi, Shashank; Khoubrouy, SoudehInflammatory biomarkers are modulated due to an infection or inflammatory trigger. Cytokines are inflammatory biomarkers that orchestrate the manifestation and progression of an infection/inflammatory event. Hence, non-invasive, real-time monitoring of cytokines can be pivotal in assessing the progression of infection/inflammatory event. However, real-time monitoring of biomarkers is not feasible with the current technology as most of them rely on blood-based detection. Continuous monitoring of host immune markers in sweat can aid in realtime monitoring of the immune status. This dissertation demonstrates a wearable SWEATSENSER device that can track the levels of immune cytokine markers in real-time from passively expressed sweat. The developed device is of a watch form-factor that can be worn on the arm to reliably track the biomarker response from low volumes of sweat (~1 μL) and the biomarker levels can be monitored in real-time. The developed SWEATSENSER device was validated for reliably reporting the levels of several cytokines and chemokines. Additionally, this work presents a thorough validation on the presence of certain critical infection and inflammatory markers such as interferon-inducible protein (IP-10) and tumor necrosis factor- related apoptosis-inducing ligand (TRAIL), C-reactive protein that make it feasible for using sweat as a biofluid for actively monitoring the health status. Additionally, human subject clinical studies demonstrate the feasibility of non-invasively tracking infections such as influenza from sweat. Such a wearable device can offer significant strides in improving prognosis and provide personalized therapeutic treatment for several inflammatory/infectious diseases.Item Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics(Springer, 2018-10-08) Patnaik, Sourav S.; Simionescu, Dan T.; Goergen, Craig J.; Hoyt, Kenneth; Sirsi, Shashank; Finol, Ender A.; Hoyt, Kenneth; Sirsi, ShashankPentagalloyl glucose (PGG) is an elastin-stabilizing polyphenolic compound that has significant biomedical benefits, such as being a free radical sink, an anti-inflammatory agent, anti-diabetic agent, enzymatic resistant properties, etc. This review article focuses on the important benefits of PGG on vascular health, including its role in tissue mechanics, the different modes of pharmacological administration (e.g., oral, intravenous and endovascular route, intraperitoneal route, subcutaneous route, and nanoparticle based delivery and microbubble-based delivery), and its potential therapeutic role in vascular diseases such as abdominal aortic aneurysms (AAA). In particular, the use of PGG for AAA suppression and prevention has been demonstrated to be effective only in the calcium chloride rat AAA model. Therefore, in this critical review we address the challenges that lie ahead for the clinical translation of PGG as an AAA growth suppressor.Item Routing in Solar-powered UAV Delivery System(2022-08-01T05:00:00.000Z) Tian, Zijing; Sirsi, Shashank; Haas, Zygmunt; Du, Ding-Zhu; Faragó, András; Huynh, Dung T.As interest grows in Unmanned Aerial Vehicles (UAVs) systems, UAVs are proposed to take on increasingly more tasks that were previously assigned to humans. One such task is the delivery of goods within urban cities using UAVs, which would otherwise be delivered by terrestrial means. However, the limited endurance of UAVs due to limited onboard energy storage makes it challenging to practically employ the UAV technology for deliveries across long routes. Furthermore, the relatively high costs of building UAV charging stations prevent dense deployment of charging facilities. Solar-powered UAVs can ease this problem as they do not require charging stations and can harvest solar power in the daytime. This paper introduces a solar- powered UAV goods delivery system to plan delivery missions by Solar-Powered UAVs (SPUs). In this study, when the SPUs run out of power, they will charge themselves on landing places provided by customers instead of charging stations. Some advanced path planning algorithms are proposed to minimize the overall mission time in the statical charging efficiency environment. We further consider routing in the dynamical charging efficiency environment and propose some mission arrangement protocols to manage different missions in the system. The simulation results demonstrate that the algorithms proposed in our work perform significantly better than existing UAV path planning algorithms in solar-powered UAV systems.