Biomedical Engineering and Bioengineering Commons^™

Characterization Of Influenza-Specific Antibodies, Xinping Ran

ENGS 86 Independent Projects (AB Students)

Influenza viruses cause respiratory illness that affects 8% of the U.S. population annually. However, current influenza vaccines have a limited efficacy of only 40-60%. This highlights the need for a universal vaccine design that can generate broadly neutralizing antibodies against influenza surface protein hemagglutinin (HA). Previous work by our group identified HA-specific monoclonal antibodies (mAbs) from serum samples through high-throughput antibody profiling. In this study, three of the identified mAbs were generated using mammalian cell expression and their binding affinity against three HA antigens was characterized via Enzyme-Linked Immuno-Sorbent Assay (ELISA). The ELISA results demonstrated specific binding affinity towards B/Yamagata/18/1998 …

The Discovery, Characterization, And Engineering Of Autolytic Enzymes As Antimicrobials, Jacob M. Furlon

Dartmouth College Ph.D Dissertations

In an age of rising levels of antibiotic resistance, we are quickly running out of tools to address some of the most virulent and widespread infectious bacteria. One group of enzymes that show significant potential for use as next-generation antibiotics are antimicrobial peptidoglycan hydrolases, often referred to as lysins. These enzymes are responsible for the breakdown of peptidoglycan within the bacterial cell wall, and, when exogenously applied, can result in dramatic destabilization of the cell wall leading to rapid lysis of the bacteria. While phage endolysins have been widely investigated as potential antimicrobials, the therapeutic potential of endogenous autolysins from …

Design Of Asic Based Electrical Impedance Tomography Microendoscopic System For Prostate Cancer Surgical Marginal Assessment, Mohsen Shahghasemi

Dartmouth College Ph.D Dissertations

Prostate cancer is the second most common cancer in the United States. It is typically treated by surgically excising the cancerous section of the prostate. Because there is not always a visible distinction between the healthy and cancerous sections, surgery often leaves some cancerous tissue behind. This is referred to as a positive surgical margin and it requires adjuvant treatment with adverse side effects. Electrical impedance tomography (EIT) is a low-cost low-form-factor method that can be used to assess surgical marginal intraoperatively to ensure that no cancerous tissue is left behind. EIT-based surgical margin assessment works on the principle that …

System-Characterized Artificial Intelligence Approaches For Cardiac Cellular Systems And Molecular Signature Analysis, Ziqian Wu

Dartmouth College Ph.D Dissertations

The dissertation presents a significant advancement in the field of cardiac cellular systems and molecular signature systems by employing machine learning and generative artificial intelligence techniques. These methodologies are systematically characterized and applied to address critical challenges in these domains. A novel computational model is developed, which combines machine learning tools and multi-physics models. The main objective of this model is to accurately predict complex cellular dynamics, taking into account the intricate interactions within the cardiac cellular system. Furthermore, a comprehensive framework based on generative adversarial networks (GANs) is proposed. This framework is designed to generate synthetic data that faithfully …

Intraoperative Quantification Of Bone Perfusion In Lower Extremity Injury Surgery, Xinyue Han

Dartmouth College Ph.D Dissertations

Orthopaedic surgery is one of the most common surgical categories. In particular, lower extremity injuries sustained from trauma can be complex and life-threatening injuries that are addressed through orthopaedic trauma surgery. Timely evaluation and surgical debridement following lower extremity injury is essential, because devitalized bones and tissues will result in high surgical site infection rates. However, the current clinical judgment of what constitutes “devitalized tissue” is subjective and dependent on surgeon experience, so it is necessary to develop imaging techniques for guiding surgical debridement, in order to control infection rates and to improve patient outcome.

In this thesis work, computational …

Leveraging Magnetic Nanoparticles And Photothermal Heating For On-Chip Processing Of Therapeutic Exosomes, Siddhant Parwal

Engineering Undergraduate Senior Theses

Drug delivery is a key area of therapeutic development that focuses on delivery of active agents to target tissues while minimizing off-target toxicities. Current methods have drawbacks including immunogenicity and suboptimal tissue targeting. Exosomes have gained attention as an ideal delivery molecule due to their high biocompatibility, cargo agnostic nature, and innate targeting ability. The current roadblock for exosomes as a therapeutic modality is the unscalable and inefficient manufacturing paradigm.

We validate a developed microfluidic device for integrated isolation and therapeutic loading of exosomes from native biofluid. The developed system captures exosomes by use of anti-exosome antibodies conjugated to magnetic, …

Piezoelectric And Conductive Polymer Based Flexible Devices Enabling Cardiovascular Health Sensing And Energy Harvesting, Andrew Closson

Dartmouth College Ph.D Dissertations

Piezoelectric materials show great promise for low-power wearable and implantable sensing, but their rigidity makes it challenging to integrate them with biological tissue. To address this, researchers have started exploring polymer-based functional materials that offer flexibility and are suitable for interfacing with the human body. However, these materials are still in their early stages, and a framework is necessary to illustrate how these materials, in conjunction with novel fabrication techniques and device designs, can enable the development of multi-functional sensing and energy harvesting devices.

This thesis utilizes highly scalable fabrication methods for functional polymers to build and test a flexible …

Soil Respiration Measurements Reveal High Retention Of Organic Carbon From Corn Residue Derived High-Lignin Fermentation Byproduct Enabling Sustainable Lignocellulosic Biofuel Production, Michelle Sun Wang

Dartmouth College Master’s Theses

While 2G biofuel production can utilize non-edible, lignocellulosic feedstocks such as agricultural residues to produce liquid fuel, harvesting crop residues is unsustainable without careful management of the soil underneath. By harvesting a fraction of the crop residues left in the field after harvest, soil health can diminish and critically, the soil organic carbon (SOC) stored in agricultural fields can decrease. Currently, in the most popular 2G process models published, the issue of soil degradation remains unresolved with residue harvest strategies receiving considerable attention in the literature and other SOC management strategies receiving far less. Specifically, the strategy of returning the …

Deutj: An Imagej Plugin For Improved Automatic Masking And Segmentation Of Images From Confocal Microscopy, Sunny Cui

Independent Student Projects and Publications

Due to advances in microscopic imaging, there are a plethora of biological molecules that can now be tagged and subsequentially imaged from almost any cell, organism, or tissue. However, the ability of software to analyze these images remains to be a challenge. ImageJ is open source software that allows for the processing of these images, but faces challenges when dealing with images that show weak contrast between objects of interest and background. DeutJ is an ImageJ plugin that color corrects and brightness corrects gradients that inhibit segmentation in confocal microscopy images. It can analyze hundreds of images from a given …

Zinc Oxide Based Nanomaterials And Device Designs - For Bioenergy Harvesting, Sensing And Water Purification, Congran Jin

Dartmouth College Ph.D Dissertations

Biomechanical energy harvested from the human body can power implantable electronics such as cardiac pacemakers, replacing conventional batteries and offering a lifelong energy solution. The electrical signals converted from biomechanical motions contain vital physiological information, making them suitable as a sensor to monitor one's health condition. Zinc Oxide (ZnO) is a versatile material with various intriguing properties, including piezoelectricity, photo-catalytic and piezo-catalytic properties. This thesis aims to exploit and enhance these properties of ZnO by rationally designing its nano- and micron-structures and employing them, along with other functional materials, in the development of novel biomechanical energy harvesting, water purification, and …

High Throughput Cellular Screening Technologies For Engineering Enhanced-Solubility And Deimmunized Biologics, Andrew Y. Chang

Dartmouth College Ph.D Dissertations

High throughput cell-based screening methodologies have become core development tools for the generation and engineering of various biotherapeutics. For example, SpCas9 variants for use in CRISPR-Cas9 therapeutics have been engineered for enhanced specificity using a high throughput directed evolution approach in E. coli. Additionally, antibodies are routinely discovered and engineered for high affinity binding using yeast surface display. These high throughput techniques typically involve generation of large protein libraries which require innovative screening strategies depending on the target protein’s function. In this thesis work, we describe high throughput protein library screening approaches to address recombinant biologic aggregation and immunogenicity …

Advanced Tools For Time-Resolved Imaging Of Tissue Metabolism, Arthur Petusseau

Dartmouth College Ph.D Dissertations

Medical imaging is a crucial tool in diagnosing and treating diseases, and by far the most common set of tools used for point-of-care guidance between a physician and patient are optical devices. For example, visible light imaging has unique applications in endoscopy, dermatology, microscopy, and this range of devices utilize a wide range of optical signals for sensing the tissue. Fluorescence imaging has become a niche but growing methodology in medical diagnostics and treatment because of its simplicity and the ability to integrate reporter molecules, that can reveal detailed information about cellular structures, metabolism, signaling, and other biomolecular features of …

Design Of Next-Generation Neural Interfaces For Decoding The Brain, Yi Qiang

Dartmouth College Ph.D Dissertations

The primary goal of neural interface technology is to establish a connection between the nervous system and the external world by recording and modulating neural signals. Over the past few decades, microelectrode array (MEA) technology has played an essential role in the acquisition of electrophysiological signals, with impressive progress being made towards developing high-density, large-throughput, and ultra-flexible MEAs. However, despite these advancements, there remain long-standing limitations in current neural interfaces. For example, electrophysiology is limited in its ability to distinguish cell types and has limited spatial resolution due to its electrical recording nature. Furthermore, conventional neural MEAs are limited to …

Mechanical Design Of A Microwave Imaging Device For Breast Cancer Detection In Mri Scanners, Grace M. Player

Dartmouth College Master’s Theses

This project seeks to develop an updated version of a microwave imaging device for use in conjunction with breast MRI, improving upon existing technology and developing novel concepts for the device. It posits three primary redesign targets for updating the previous system: resizing the system height, making the device more iteration- friendly, and improving the overall manufacturability of the device by replacing custom components with commercially available alternatives. All three of these redesign targets are met in the new design, V2.0. The height is reduced by reducing antenna travel and height, embedding some components, and shortening the tank wall, resulting …

Using Paired-Agent Imaging To Track Changes In Head And Neck Cancers After Undergoing Photodynamic Therapy Treatment, Reeham M. Choudhury

Dartmouth College Master’s Theses

Head and neck cancers affect thousands of people across the world, and photodynamic therapy (PDT) has been shown to have great potential to treat said cancers in a noninvasive manner. However, imaging head and neck cancers has been difficult, and molecular changes caused by PDT are not well-understood. Therefore, we propose the use of paired-agent imaging (PAI) to track changes in these cancers after after PDT treatment. For these studies, we primarily used benzoporphyrin derivative monoacid (BPD) for our photosensitizer, which is activated by a 690 nm laser. We first looked at changes in EGFR expression in vitro, and …

Advancing Fluorescent Contrast Agent Recovery Methods For Surgical Guidance Applications, Brook Kennedy Byrd

Dartmouth College Ph.D Dissertations

Fluorescence-guided surgery (FGS) utilizes fluorescent contrast agents and specialized optical instruments to assist surgeons in intraoperatively identifying tissue-specific characteristics, such as perfusion, malignancy, and molecular function. In doing so, FGS represents a powerful surgical navigation tool for solving clinical challenges not easily addressed by other conventional imaging methods. With growing translational efforts, major hurdles within the FGS field include: insufficient tools for understanding contrast agent uptake behaviors, the inability to image tissue beyond a couple millimeters, and lastly, performance limitations of currently-approved contrast agents in accurately and rapidly labeling disease. The developments presented within this thesis aim to address such …

Color Resolved Cherenkov Imaging Allows For Differential Signal Detection In Blood And Melanin Content, Vihan A. Wickramasinghe

Dartmouth College Master’s Theses

Cherenkov imaging in radiation therapy allows a video display of the irradiation beam on the patient’s tissue, for visualization of the treatment. High energy radiation from a linear accelerator (Linac) results in the production of spectrally-continuous broadband light inside tissue due to the Cherenkov effect; this light is then attenuated by tissue features from transport and exits from the delivery site. Progress with the development of color Cherenkov imaging has opened the possibility for some level of spectroscopic imaging of the light-tissue interaction and interpretation of the specific nature of the tissue being irradiated. Generally, there is a linear relationship …

Expanding Cherenkov Imaging Applications In Radiotherapy: Clinic-Wide In Vivo Treatment Monitoring And Mr-Linac Quality Assurance, Daniel A. Alexander

Dartmouth College Ph.D Dissertations

Radiation therapy treatments have become increasingly complex, striving to improve patient outcomes by delivering sufficient dose for tumor control while sparing more normal tissue. This trend has necessitated the development of additional workflows, such as multilayered incident mitigation strategies and advanced techniques for adapting treatments to account for time-sensitive patient factors. Novel technologies such as optical 3D surface monitoring and magnetic resonance-guided linear accelerators have been developed to assist clinicians in implementing these workflows. We hypothesize that optical imaging methods developed for radiotherapy dose monitoring and measurement can be used to positively impact modern radiation therapy challenges. Cherenkov imaging allows …

Multimodal Ultrasound Imaging For Improved Metastatic Lymph Node Detection, Sidhartha Jandhyala

Dartmouth College Ph.D Dissertations

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is complex in nature due to the variety of organs located in the head and neck region. Knowing the metastatic state of the lymph nodes is paramount in accurately staging and treating HNSCC patients. Currently, metastatic lymph node detection involves the use of magnetic resonance imaging and/or x-ray computed tomography, followed by biopsies for histological confirmation. The main diagnostic criteria is the size of the nodes; however, current imaging methods are not 100% accurate due natural lymph node variability. Ultrasound imaging is able to provide …

Advancing Combined Radiological And Optical Scanning For Breast-Conserving Surgery Margin Guidance, Samuel Stewart Streeter

Dartmouth College Ph.D Dissertations

Breast cancer is one of the most common types of cancer worldwide, and standard-of-care for early-stage disease typically involves a lumpectomy or breast-conserving surgery (BCS). BCS involves the local resection of cancerous tissue, while sparring as much healthy tissue as possible. State-of-the-art methods for intraoperatively evaluating BCS margins are limited. Approximately 20% of BCS cases result in a tissue resection with cancer at or near the resection surface (i.e., a positive margin). A two-fold increase in ipsilateral breast cancer recurrence is associated with the presence of one or more positive margins. Consequently, positive margins often necessitate costly re-excision procedures to …

Phase-Changing Nanodroplets As Nanotheranostic Platform For Combination Cancer Therapy, Catalina-Paula Spatarelu

Dartmouth College Ph.D Dissertations

Cancer is a cluster of diseases, and 1.8 million Americans are newly diagnosed each year. Treatment issues such as drug instability, the occurrence of severe side effects, as well as resistance make the need for solutions to improve conventional methods, like chemotherapy, apparent. Nano-sized drug-delivery platforms, particles loaded with therapeutic molecules that escape the immune system clearance and accumulate at the tumor site, were proposed as one of these solutions. Despite the expansion of the field, several aspects still need to be addressed: inconsistent delivery of the drugs, inability of measuring the effective dose being delivered to the tumor, lack …

Modeling The Effect Of Igg Subclasses And Specificity In The Translocation Of Monoclonal Antibodies Across The Placental Barrier, Sayuri Tais Miyamoto Magnabosco

ENGS 88 Honors Thesis (AB Students)

Infections are responsible for over half a million neonatal deaths every year (Lawn et al., 2014). Thus, there is huge interest in leveraging maternal immunization against infectious diseases to grant fetal protection during its development through the vertical transferring of IgG antibodies, the only Ig subclass that can significantly cross the placental barrier. Studies about vertical immunization rely on in-vitro models to extrapolate physiological conditions of the human placenta. The BeWo Transwell model (Bode et al., 2006) presents itself as a reliable model to mimic the transplacental transport mechanism of antibodies (Ellinger et al., 1999; Poulsen et al., 2009) …

Flash Radiotherapy: Skin Pigmentation As A Non-Invasive Indicator For Radiation-Induced Damage, Brady Mccallister

ENGS 88 Honors Thesis (AB Students)

FLASH ultra-high dose rate radiotherapy (RT) is one of the most rapidly growing subfields of radiation oncology today due to its potential to increase the limits of the therapeutic ratio. The FLASH effect, which includes heightened normal tissue sparing paired with iso-effective tumor cell killing, has been literature documented, in a limited manner, in rodent models, a few large animals, and one clinical patients.

A porcine-based experiment was conducted to test the effects of FLASH RT on normal tissue compared to conventional (CONV) RT. A clinical linear accelerator (LINAC) was reversibly converted to be capable of FLASH RT. A female …

Classifying Common Knee Rehabilitation Exercise Mistakes Using Imu Data, Fedor Myagkov

Dartmouth College Undergraduate Theses

Physical therapy following major surgeries is a branch of medicine that has seen its fair share of technologically inspired advances. One important facet of physical therapy, the “at-home exercises” patients are prescribed to do, is still somewhat of a “black box” to many physical therapists (PTs). PTs have no way of knowing (1) whether the patient is doing the home exercises, or (2) whether the patient is doing the exercises in the correct and healthy manner. This lack of awareness makes it difficult for the PT to guide the patient, which can often lead to prolonged rehabilitation periods or (sometimes) …

Using Natural Language Processing And Sentiment Analysis To Augment Traditional User-Centered Design: Development And Usability Study, Curtis L. Petersen, Ryan Halter, David Kotz, Lorie Loeb, Summer B. Cook, Dawna M. Pidgeon, Brock Christensen, John A. Batsis

Dartmouth Scholarship

Background: Sarcopenia, defined as the age-associated loss of muscle mass and strength, can be effectively mitigated through resistance-based physical activity. With compliance at approximately 40% for home-based exercise prescriptions, implementing a remote sensing system would help patients and clinicians to better understand treatment progress and increase compliance. The inclusion of end users in the development of mobile apps for remote-sensing systems can ensure that they are both user friendly and facilitate compliance. With advancements in natural language processing (NLP), there is potential for these methods to be used with data collected through the user-centered design process.

Objective: This study aims …

A Convolutional Neural Network For Fast Fluence Estimation In Complex Tissues, Nicholas Blasey, Geoffrey P. Luke

ENGS 88 Honors Thesis (AB Students)

Photoacoustic (PA) imaging is a non-invasive diagnostic imaging technique that gives images of photoabsorbers based on their absorption of optical energy. These optical absorption properties can then be linked to important tissue properties. For the method to be quantitative, however, it is necessary to have an accurate estimation of the light fluence in the tissue. The current gold standard in addressing the fluence estimation problem, a Monte Carlo Simulation, is costly in time and computation. In this work, we developed a deep neural network to quickly and accurately estimate light fluence in arbitrary tissue types and geometries. The network was …

Bio Circuits For Evolutionary Biotech, Camilo Toruno

ENGS 86 Independent Projects (AB Students)

The field of bioengineering has much promise for renewable chemical production, bioremediation, and of course medical applications. Developing new useful microorganisms is extremely time and capital intensive, typically taking 50 million USD and eight years. This is due in large part to the low throughput techniques that are characteristic of the field of metabolic engineering. Here we describe the modification of an existing synthetic biosensor to measure the pharmaceutical dopamine, and the use of a circuit simulator Cadence to predict improvements to the biosensor. This biosensor paired with directed evolution techniques could reach throughputs of 5 million cells per day …

Utilizing Neural Networks And Wearables To Quantify Hip Joint Angles And Moments During Walking And Stair Ascent, Megan V. Mccabe

ENGS 88 Honors Thesis (AB Students)

Wearable sensors were leveraged to develop two methods for computing hip joint angles and moments during walking and stair ascent that are more portable than the gold standard. The Insole-Standard (I-S) approach replaced force plates with force-measuring insoles and achieved results that match the curvature of results from similar studies. Peaks in I-S kinetic results are high due to error induced by applying the ground reaction force to the talus. The Wearable-ANN (W-A) approach combines wearables with artificial neural networks to compute the same results. Compared against the I-S, the W-A approach performs well (average rRMSE = 18%, R^{2 …}

C-Molecules: Molecular-Guided Surgery With Fluorescence Imaging, Riley Karp, Joshua Gutow, William Wolfe-Mcguire

ENGS 89/90 Reports

Surgeries may cost lives if performed inadequately, which is why tools such as fluorescence guided surgery exist to improve surgical outcomes. Fluorescence guided surgery (FGS) is the practice of injecting patients with a fluorescent molecule that, in combination with highly sensitive cameras, allows surgeons to clearly identify complex biological structures. While beneficial in procedures such as endoscopy and gallbladder surgery, this technique is most notable for its role in complex cancer surgeries where misidentifying the boundaries of a tumor can have deadly consequences. Although FGS has the potential to revolutionize cancer treatment, highly sensitive imaging systems are necessary to identify …

Developing A Control System To Better Understand The Effects Of Pyruvate Decarboxylase Activity On Clostridium Thermocellum Metabolism, Nicholas Cervenka

ENGS 88 Honors Thesis (AB Students)

In order for cellulosic biofuels from Clostridium thermocellum to be commercially viable, the ethanol yield and titer of the microbe must be increased. To accomplish this, it has been suggested to introduce the Pyruvate Decarboxylase (PDC) enzyme into C. thermocellum. In order to demonstrate effects on ethanol production by PDC prior to genetic modification, a cell free system (CFS) has been developed. A purified enzyme system was developed with the CFS to function as a control. Using the purified enzyme system, PDC from Saccharomyces cerevisiae was demonstrated to be a good candidate for further testing in the CFS.