Engineering Commons^™

Rapid Thermocycler System For Rapid Amplification Of Nucleic Acids And Related Methods, Joel R. Termaat, Scott E. Whitney, Hendrik J. Viljoen, Matthew R. Kreifels

Department of Chemical and Biomolecular Engineering: Patents

A thermocycling device and method of operating a thermocycler instrument, the instrument including a sample holder, at least one thermal cycling element, and at least one first and second temperature sensors, for causing the sample holder containing the at least one sample to undergo polymerase chain reaction amplification by repeated cycling between at least a denaturation heating stage and an aunealing cooling stage. The first temperature corresponding with the temperature of the sample holder is monitored using the at least one first temperature sensor, and a second temperature corresponding with the temperature external of the sample holder is monitored using …

Development And Validation For A Mobile Speech-In-Noise Audiometric Task, Tommy Peng

McKelvey School of Engineering Graduate Student Theses & Dissertations

Traditional speech-in-noise hearing tests are performed by clinicians with specialized equipment. Furthermore, these tasks often present contextually weak sentences in background babble, which are poor representations of real-world situations. This study proposes a mobile audiometric task, Semantic Auditory Search, which uses the Android platform to bypass the need for specialized equipment and presents multiple tasks of two competing real-world conversations to estimate the user’s speech-in-noise hearing ability. Through linear regression models built from data of seventy-nine subjects, three Semantic Auditory Search metrics have been shown to have statistically significant (p < 0.05) with medium effects sizes for predicting QuickSIN SNR50. The internal consistency of the task was also high, with a Cronbach’s alpha of 0.88 or more across multiple metrics. In conclusion, this preliminary study suggests that Semantic Auditory Search can accurately and reliably perform as an automated speech-in-noise hearing test. It also has tremendous potential for extension into automated tests of cognitive function, as well.

Performance Assessment Of Diffuse Optical Spectroscopic Imaging Instruments In A 2-Year Multicenter Breast Cancer Trial, Anais Leproux, Thomas D.O. Sullivan, Albert E. Cerussi, Amanda Durkin, Brian Hill, Nola M. Hylton, Arjun G. Yodh, Stefan A. Carp, David A. Boas, Shudong Jiang, Keith D. Paulsen, Brian W. Pogue, Darren M. Roblyr, Wei T. Yang, Bruce J. Tromberg

Dartmouth Scholarship

We present a framework for characterizing the performance of an experimental imaging technology, diffuse optical spectroscopic imaging (DOSI), in a 2-year multicenter American College of Radiology Imaging Network (ACRIN) breast cancer study (ACRIN-6691). DOSI instruments combine broadband frequency-domain photon migration with time-independent near-infrared (650 to 1000 nm) spectroscopy to measure tissue absorption and reduced scattering spectra and tissue hemoglobin, water, and lipid composition. The goal of ACRIN-6691 was to test the effectiveness of optically derived imaging endpoints in predicting the final pathologic response of neoadjuvant chemotherapy (NAC). Sixty patients were enrolled over a 2-year period at participating sites and received …

Robust Odorant Recognition In Biological And Artificial Olfaction, Nalin Katta

McKelvey School of Engineering Graduate Student Theses & Dissertations

Accurate detection and identification of gases pose a number of challenges for chemical sensory systems. The stimulus space is enormous; volatile compounds vary in size, charge, functional groups, and isomerization among others. Furthermore, variability arises from intrinsic (poisoning of the sensors or degradation due to aging) and extrinsic (environmental: humidity, temperature, flow patterns) sources. Nonetheless, biological olfactory systems have been refined over time to overcome these challenges. The main objective of this work is to understand how the biological olfactory system deals with these challenges, and translate them to artificial olfaction to achieve comparable capabilities. In particular, this thesis focuses …

Photodynamic Therapy: Agents And Mechanisms, Rebecca Claire Gilson

McKelvey School of Engineering Graduate Student Theses & Dissertations

Despite enormous efforts, cancer remains a leading cause of morbidity and mortality world-wide. The main challenges currently facing cancer therapy include lack of adequate tumor targeting, failure to treat hypoxic tumor cells, and induction therapy resistant tumors. A solution to these limitations can be found in photodynamic therapy (PDT) which combines light and light activatable compounds, photosensitizers (PSs), to produce cytotoxic reactive oxygen species (ROS) to damage tumor tissue. This creates a spatiotemporal therapeutic effect, where cell damage only occurs at the intersection of the PS and light. PDT can treat tumors through unique mechanisms which reduce induction of tumor …

Development Of High Resolution Tools For Investigating Cardiac Arrhythmia Dynamics, Christopher Reed Gloschat

McKelvey School of Engineering Graduate Student Theses & Dissertations

Every year 300,000 Americans die due to sudden cardiac death. There are many pathologies, acquired and genetic, that can lead to sudden cardiac death. Regardless of the underlying pathology, death is frequently the result of ventricular tachycardia and/or fibrillation (VT/VF). Despite decades of research, the mechanisms of ventricular arrhythmia initiation and maintenance are still incompletely understood.

A contributing factor to this lack of understanding is the limitations of the investigative tools used to study VT/VF. Arrhythmias are organ level phenomena that are governed by cellular interactions and as such, near cellular levels of resolution are needed to tease out their …

Intrinsic And Extrinsic Biomechanical Factors In A Co-Adaptive Ecog-Based Brain Computer Interface, Jonathan Carl Landes

McKelvey School of Engineering Graduate Student Theses & Dissertations

Paralysis, due to spinal cord injury, amyotrophic lateral sclerosis (ALS), or stroke, is the result of severed communication between the brain and the motor periphery. Brain computer interfaces (BCIs) are neuroprosthetic devices that create novel communication pathways by measuring and transforming neural activity into operational commands. State of the art BCI systems measure brain activity using penetrating electrode arrays able to record from hundreds of individual cortical neurons simultaneously. Unfortunately, these systems are highly susceptible to signal degradation which limits their efficacy to 1-2 years. However, electrocorticography (ECoG) signals recorded from the surface of the brain deliver a more competitive …

Designing Metabolite Biosensors And Engineering Genetic Circuits To Regulate Metabolic Pathways, Di Liu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Microbial production of chemicals has provided an attractive alternative to chemical synthesis. A key to make this technology economically viable is to improve titers, productivities, and strain robustness. However, pathway productivities and yields are often limited by metabolic imbalances that inhibit cell growth and chemical production. In contrast, natural metabolic pathways are dynamically regulated according to cellular metabolic status. Dynamic regulation allows cells to adjust metabolite concentrations to optimal levels and avoid wasting carbon and energy. Inspired by nature, synthetic regulatory circuits have shown great promise in improving titers and productivities, because they can balance the metabolism by dynamically adjusting …

Improving Pure-Tone Audiometry Using Probabilistic Machine Learning Classification, Xinyu Song

McKelvey School of Engineering Graduate Student Theses & Dissertations

Hearing loss is a critical public health concern, affecting hundreds millions of people worldwide and dramatically impacting quality of life for affected individuals. While treatment techniques have evolved in recent years, methods for assessing hearing ability have remained relatively unchanged for decades. The standard clinical procedure is the modified Hughson-Westlake procedure, an adaptive pure-tone detection task that is typically performed manually by audiologists, costing millions of collective hours annually among healthcare professionals. In addition to the high burden of labor, the technique provides limited detail about an individual’s hearing ability, estimating only detection thresholds at a handful of pre-defined pure-tone …

Composition-Dependent Mechanisms Of Multiscale Tendon Mechanics, Fei Fang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Tendons serve as an integral part of the musculoskeletal system by transferring loads from muscle to bone and providing joint mobility and stability. From the physiologically-loading perspective, while progress has been made in evaluating mechanical behavior of different types of tendons in tension, further work is needed to relate tendon mechanics to compositional and microstructural properties, particularly under non-tensile loading modalities (i.e., shear, compression). This information is vital to explore mechanisms of how mechanical signals lead to changes in tendon structure and composition to enable these tissues to function properly, including in in vivo multiaxial loading conditions. From the structural …

Mechanobiology Of Epithelial Clusters In Ecms Of Diverse Mechanical Properties, Samila Nasrollahi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cell clusters reside in complex extracellular matrices (ECMs) of varying mechanical properties. Epithelial cells sense and translate the mechanical cues presented by the surrounding ECM into biochemical signals through a process called ‘mechanotransduction’, which controls fundamental aspects of disease and development. During the course of metastasis, mechanical changes in the tumor microenvironment can lead to declustering of epithelial cells through a process called epithelial-to-mesenchymal transition (EMT). Throughout different steps of metastasis, escaped epithelial clusters encounter heterogeneous tissues of varying mechanical properties that ultimately influence their behavior in distant locations within the body. This dissertation investigates the mechanobiology of epithelial clusters …

Removal Of Retained Electrospinning Solvent Prolongs Drug Release From Electrospun Plla Fibers, Anthony R. D'Amato, Nicholas J. Schaub, Jesus M. Cardenas, Andrew S. Fiumara, Paul M. Troiano, Andrea Fischetti, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

A major challenge in developing drug-releasing electro spun nanofibers is obtaining long-term drug release over many weeks with no burst release of drug. Here, we present new methods capable of prolonging the diffusive release of small molecule drugs from electro spun poly-L-lactic acid (PLLA) nanofibers. The methods focus on removal of retained electrospinning solvent through fiber heating, maintaining fibers in a laboratory setting, or a combination of these methods. These post-fabrication methods altered the release characteristics of a model small molecule drug, 6-aminonicotinamide (6AN), from PLLA fibers. Specifically, untreated fibers released 6AN over 9 days, and fibers that underwent a …

Preclinical Evaluation Of Spatial Frequency Domain-Enabled Wide-Field Quantitative Imaging For Enhanced Glioma Resection, Mira Sibai, Carl Fisher, Israel Veilleux, Jonathan T. Elliot, Frederic Leblond, David W. Roberts, Brian Wilson

Dartmouth Scholarship

5-Aminolevelunic acid-induced protoporphyrin IX (PpIX) fluorescence-guided resection (FGR) enables maximum safe resection of glioma by providing real-time tumor contrast. However, the subjective visual assessment and the variable intrinsic optical attenuation of tissue limit this technique to reliably delineating only high-grade tumors that display strong fluorescence. We have previously shown, using a fiber-optic probe, that quantitative assessment using noninvasive point spectroscopic measurements of the absolute PpIX concentration in tissue further improves the accuracy of FGR, extending it to surgically curable low-grade glioma. More recently, we have shown that implementing spatial frequency domain imaging with a fluorescent-light transport model enables recovery of …

Fundamental Characterization Of Oxygen Nanobubbles, John Hamlin, Yi Wen, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

A hypoxic environment is created by tumors’ incredible growth rate. Hypoxia provides radioresistance to the tumors, thus making radiation treatment less effective. The issue is that increasing the radiation leads to increased side effects in patients. Our goal for the oxygen-filled nanobubble is to deliver oxygen to the tumor to lessen radioresistance and make radiation treatment more efficient. However, we need preliminary research to understand and improve the nanobubbles before further research and implementation. To do this, we synthesized different batches of nanobubbles to optimize the production method and find the best container and temperature to store nanobubbles. We measured …

Smartphone-Based Microscope For Pathogen Detection, Meghan E. Henderson, Katherine N. Clayton, Ryan M. Preston, Jacqueline Linnes, Tamara L. Kinzer-Ursem

The Summer Undergraduate Research Fellowship (SURF) Symposium

Vibrio cholerae is a water and food borne bacteria that causes cholera, a severe acute diarrheal disease, when ingested and when left untreated, can cause patient death within hours. Currently there is a lack of both sensitive and rapid portable detection technologies of V. cholerae for testing water and food samples. Combining nucleic acid amplification and particle diffusometry present an alternative detection method for V. cholerae in under 30 minutes, but the process requires an expensive laboratory microscope. In this work, we develop a smartphone-based microscope to detect V. cholerae DNA in environmental water samples using particle diffusometry. A modular …

Gui For Mri-Compatible Neural Stimulator And Recorder, Soo Han Soon, Nishant Babaria, Ranajay Mandal, Zhongming Liu

The Summer Undergraduate Research Fellowship (SURF) Symposium

Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are useful tools to analyze brain activities given active stimulation. However, the electromagnetic noise from the MRI distorts the brain signal recording and damages the subject with excessive heat generated on the electrodes attached to the skin. MRI-compatible recording and stimulation systems previously developed at LIBI lab were capable of removing the electromagnetic noise during the imaging process. Previously, the hardware systems had required the integrative software that could control both circuits simultaneously and enable users to easily change recording and stimulation parameters. Graphical user interface (GUI) programmed with computer language informed …

How Strongly Do Oysters Stick?, Nicolás M. Morato, Andrés M. Tibabuzo, Jonathan J. Wilker

The Summer Undergraduate Research Fellowship (SURF) Symposium

Biological adhesives are a type of interfacial material that has incredible potential to generate new biomimetic compounds that can replace current strong, but toxic, adhesives. Therefore, a study of the chemical composition and mechanical properties of those bio-adhesives is necessary. However, in the case of oysters, despite known chemical characterization of the adult’s adhesive, there are almost no studies on its mechanical properties. Furthermore, there is no available information on the adhesive properties of spat (oysters in their larvae state). Herein, we present the first mechanical characterization of the spat adhesive, measuring its adhesion strength by hydrodynamic determination using a …

Low Power, Low Noise Circuit For Biological Signal Recording, Rachael A. Swenson, Daniel J. Pederson, Pedro Irazoqui

The Summer Undergraduate Research Fellowship (SURF) Symposium

Implantable devices are ideal for recording biological signals in animal models as they have minimal effect on the animal’s normal behavior during observation. The creation of the circuitry for an implantable device has several restrictions including size, power consumption, and noise reduction. These factors compete against each other, making it necessary to carefully optimize circuit components for a given application. This study evaluates the design of a four-channel analog front end circuit board to record cardiac, neural, and respiratory biological signals. Through a critical analysis of component specifications for the circuit’s components and an evaluation of the circuits’ power and …

Temporal Resolution Of Cell Death Signaling Events Induced By Cold Atmospheric Plasma And Electroporation In Human Cancer Cells, Danielle M. Krug, Prasoon K. Diwakar, Ahmed Hassanein

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cancer treatment resistance and their invasive and expensive nature is propelling research towards developing alternate approaches to eradicate cancer in patients. Non-thermal, i.e., cold atmospheric plasma (CAP) and electroporation (EP) applied to the surface of cancerous tissue are new methods that are minimally invasive, safe, and selective. These approaches, both independently and synergistically, have been shown to deplete cancer cell populations, but the signaling mechanisms of death and their timelines of action are still widely unknown. To better understand the timeframe of signaling events occurring upon treatment, human cancer cell lines were treated with CAP, EP, and combined CAP with …

Effects Of Stroma On Er+ Breast Cancer Cell Metastasis, Shipeng Xu, Luis Solorio, Sarah Calve

The Summer Undergraduate Research Fellowship (SURF) Symposium

Breast cancer is one of the most wide-spread diseases among women in America. If the cancer is local, it is easily controlled by surgical resection. However, if the cancer cells metastasize, patient survival is significantly reduced. 70% of breast cancers can be targeted through estrogen receptors (ER) on the membrane, with compounds such as tamoxifen. However, tamoxifen shows unreliable outcomes on different patients and it is believed that the ineffectiveness of tamoxifen is related to the epithetical-mesenchymal transition (EMT) of cancer cells. To address this problem, we are designing a system that stimulates metastasis activation with the aim of incorporating …

Dual-Tuned Removable Common-Mode Current Trap For Mri, Angel G. Enriquez, Joseph V. Rispoli

The Summer Undergraduate Research Fellowship (SURF) Symposium

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are preferred methods of gathering information from the body due to their non-invasive approach of obtaining a diagnosis. MRI can obtain spatial mappings from a region of interest, while MRS can obtain metabolic information from different elements. Dual-tuned radiofrequency (RF) coils are able to capture signals produced by both hydrogen atoms and a second atom of interest. Unwanted shield currents occur in these scans, which can cause image distortion, while the high energy dissipated can create harmful heat, which can injure the patient. These shield currents, also known as common-mode currents, …

Three-Dimensional Microfluidic Tumor Vascular Model For Investigating Breast Cancer Metastasis, Anastasiia Vasiukhina, Brian H. Jun, Luis Solorio, Pavlos P. Vlachos

The Summer Undergraduate Research Fellowship (SURF) Symposium

Metastasis is one of the primary reasons for the high mortality rates in female patients diagnosed with breast cancer. It involves the migration of cancer cells into the circulatory system allowing for the dissemination of cancer cells in distal tissues. Understanding the major processes that occur in cells and tissues during metastasis can help improve currently existing therapeutic methods. In order to understand such mechanisms, developing physiologically relevant tissue models is crucial. Advancements in microfluidics have led to the fabrication of 3D culture models with shear stress gradients and flow control that can recapitulate aspects of the tumor microenvironment in …

Localized Immunosuppression Therapy For Islet Cell Encapsulation, Madeline Mclaughlin, Clarissa Stephens, Sherry Voytik-Harbin

The Summer Undergraduate Research Fellowship (SURF) Symposium

Type 1 diabetes, an autoimmune disease in which the body’s immune system destroys the insulin-producing beta cells necessary for managing a person’s blood glucose levels, affects 1.25 million Americans. A potential treatment for this disease is islet cell transplantation where Islets of Langerhans, containing the beta cells, are transplanted from a normal donor to a diabetic recipient to regulate blood glucose levels and provide insulin independence. Similar to whole organ transplantation, immune modulation through immunosuppression therapy is necessary for successful transplantation of islets without rejection. However, long-term systemic immunosuppression therapy can be toxic to the patient and the islets. Because …

Acoustic Analysis Of Vocalizations For Detecting Separation Anxiety In Dogs, Karina Sequera, Nan Kong, Niwako Ogata

The Summer Undergraduate Research Fellowship (SURF) Symposium

Separation anxiety in dogs is a clinical condition in which a dog develops an intense dependence on their caretaker. It manifests itself in maladaptive physical and psychological behaviors that are similar to that of panic attacks in humans when the dog is isolated from its owner. These include excessive vocalizations, destructive behaviors, and in more extreme cases, self-mutilation. Currently, there are no direct ways to diagnose separation anxiety without the aid an owner’s report. To ease this diagnostic process, it would be useful to utilize a tool that can distinguish between certain vocalization patterns in dogs. Literature suggests that some …

Co-Modulation Masking Release Begins In The Auditory Periphery, Kareem R. Hussein, Agudemu Borjigan, Mark Sayles

The Summer Undergraduate Research Fellowship (SURF) Symposium

Understanding speech in noisy environments can be difficult, especially for people with hearing loss. The background noise can cover up the sounds of interest. Normally, the auditory system works to alleviate this problem by tagging and then cancelling the noise. Our experiments are aimed at understanding the mechanism of this noise cancellation process. We hypothesize that non-linear signal processing in the mammalian cochlea (the most peripheral part of the auditory system) is the basis of noise cancellation. To test this hypothesis, we measured the responses of auditory-nerve fibers (ANFs) to sounds embedded in background noise with different statistical properties. ANFs …

Development Of Portable Hyperspectral Imaging Device, Chenxi Li, Youngkee Jung, Iyll-Joon Doh, Euiwon Bae

The Summer Undergraduate Research Fellowship (SURF) Symposium

Most of the conventional hyperspectral imaging devices require sophisticated optical components, occupy a large footprint, and requires an initial capital investment for laboratories which mostly suits for laboratories benchtop system. The requirement of shipping the sample and waiting an extended period of time to get the results are the main downsides of this traditional approach. Capitalize in many specific field applications and diagnosis, portable devices provide both convenience and on-site results which are desirable for government agencies and food safety inspectors. This project was aimed to develop a low-cost, portable hyperspectral device for food safety applications. A smartphone was used …

Intrinsic Regulators Of Actomyosin Contractility Engendering Pulsatile Behaviors, Qilin Yu, Jing Li, Taeyoon Kim

The Summer Undergraduate Research Fellowship (SURF) Symposium

Actomyosin contractility regulates various biological processes including cell migration, muscle contraction, and tissue morphogenesis. Cell cortex underlying a membrane, which is a representative actomyosin network in eukaryote cells, exhibits dynamic contractile behaviors. Interestingly, the cell cortex shows reversible aggregation of actin and myosin called pulsatile contraction in diverse cellular phenomena, such as embryogenesis and tissue morphogenesis. While contractile behaviors have been studied in several in vitro experiments and computational studies, none of them demonstrated the pulsatile contraction of actomyosin networks observed in vivo. Here, we used an agent-based computational model based on Brownian dynamics to identify factors facilitating the pulsatile …

Establishing A Lung Model For Evaluation Of Engineered Lung Microbiome Therapies, Kathryn F. Atherton, Stephen Miloro, Jenna Rickus

The Summer Undergraduate Research Fellowship (SURF) Symposium

Benzene, a toxin and carcinogen found in air polluted by cigarette smoke, car exhaust, and industrial processes, is associated with the development of leukemia and lymphoma. Other than avoiding exposure, there is no current method to deter the effects of benzene. One potential strategy to prevent these effects is to engineer the bacteria of the human lung microbiome to degrade benzene. To evaluate this novel approach, we must verify that the bacteria remain viable within the lung microenvironment. To do so, lungs were harvested from rats and swabbed to determine the contents of the original lung microbiome. Then green fluorescent …

A Novel High-Throughput, High-Content Three-Dimensional Assay For Determination Of Tumor Invasion And Dormancy, Mahera M. Husain, Theodore J. Puls, Sherry Voytik-Harbin

The Summer Undergraduate Research Fellowship (SURF) Symposium

Metastasis accounts for most cancer deaths, while dormancy of tumor cells leads to unexpected cancer recurrence. These two aspects of cancer remain relatively untreatable in part because current two-dimensional (2D) methods of high-throughput drug screening cannot quantify outcomes related to these phenotypes. Three-dimensional (3D) in-vitro tumor models are a promising alternative because they better recreate the tumor microenvironment and relevant phenotypes. However, outcome measures for high-throughput screening of these systems are often limited to single measures such as metabolic activity using assays that are not standardized or optimized for 3D models. To address this gap, the objective of this work …

A Parametric Study Of The Mechanics Of Different Skin Flap Techniques, Steven J. Meza, Adrián Tepole Buganza

The Summer Undergraduate Research Fellowship (SURF) Symposium

In modern day plastic and reconstructive surgeries numerous skin flap designs have been developed and are used to close open wounds. Skin flaps are developed with the intention of imposing minimal tension in skin closure. Excessive tension can lead to poor blood flow that result in post-surgery complications such as necrosis. Currently there is no standard in choosing a skin flap design and a surgeon's choice is based personal experience. A comparison of the mechanical loading in these various designs has not yet been done. We have developed a parametric study, using finite element analysis, of two advancement skin flaps …