Biomedical Engineering and Bioengineering Commons^™

Automated Microscope Stage, Corin Nishimoto, Alison Flesch, Theo Anastos

Biomedical Engineering

This document seeks to describe the background information, customer requirements, design specifications, indications for use, selected materials, proposed budget, prototypes, final design, manufacturing processes, and testing methods regarding the CellOptimizer automated microscope stage product.

Slit Lamp Ophthalmoscope Redesign, Michael Hostetler, Austin Mattmiller, Alexis Brewer

Biomedical Engineering

The slit lamp ophthalmoscope is used by ophthalmologists for diagnosis of pathologies in the eye. The device is used for identifying ocular diseases or indications of other possible systemic diseases to treat them before the diseases progress. Redesign of the ergonomics and adjustment mechanisms of the slit lamp ophthalmoscope will attempt to improve the compatibility of the device across a greater variety of patients. The wider headrest tower of 12.75 inches, the wider table cutout of 12 inches, and the 12 inches of extension of the headrest tower creates a better ergonomic fit for the patient and doctor. The wider …

Ideomotion Gait Training Thigh Prompt, Kristin Schmidt, Elizabeth Peterson, Dalton Jennings

Biomedical Engineering

This document serves as our project report at its completion for developing thigh prompts to be used with the LiftWalker. In this document we outline our project from its beginning to end. We describe our process from understanding the background and our customer requirements, transforming these customer requirements into engineering specifications, performing the stage gate process, developing and evolving the design, testing the design, and finally drawing conclusions and making recommendations for the future.

Advanced Selection Methodologies For Dnazymes In Sensing And Healthcare Applications, Sandeep Kumar, Shikha Jain, Neeraj Dilbaghi, Amrik Singh Ahluwalia, Ashraf Aly Hassan, Ki-Hyun Kim

Department of Civil and Environmental Engineering: Faculty Publications

DNAzymes have been widely explored owing to their excellent catalytic activity in a broad range of applications, notably in sensing and biomedical devices. These newly discovered applications have built high hopes for designing novel catalytic DNAzymes. However, the selection of efficient DNAzymes is a challenging process but one that is of crucial importance. Initially, systemic evolution of ligands by exponential enrichment (SELEX) was a labor-intensive and time-consuming process, but recent advances have accelerated the automated generation of DNAzyme molecules. This review summarizes recent advances in SELEX that improve the affinity and specificity of DNAzymes. The thriving generation of new DNAzymes …

Bio-Inspired Sensing And Actuating Architectures For Feedback Control Of Civil Structures, Courtney A. Peckens, I. Cook, C. Fogg

Faculty Publications

Civil structures, such as buildings and bridges, are constantly at risk of failure due to external environmental loads, such as earthquakes or strong winds. To minimize the effects of these loads, active feedback control systems have been proposed but such systems still face numerous challenges which impede their widespread adoption. In order to overcome many of these challenges, inspiration can be drawn from the signal processing and actuating techniques employed by the biological central nervous system to develop a bio-inspired control algorithm. In this study the front-end, signal processing techniques employed by biological sensory systems, and in particular the mammalian …

Development Of An Astrocyte/Glioma Co-Culture System For Measuring Cellular Dynamics, Urna Kansakar

Doctoral Dissertations

Gliomas are brain tumors that primarily arise from glial cells. Gliomas account for 70% of the brain tumors and they are more prevalent in older adults. About 60% of the people with gliomas experience at least one seizure. Brain tumors can grow and metastasize to neighboring areas, thereby destroying normal brain cells. In a brain tumor microenvironment, both malignant cancer cells and healthy brain cells are present. Studies have shown that astrocytes may have a role in tumor growth in the brain. Monocultures cannot evaluate interactions between two cell types and does not accurately represent in vivo conditions. Thus, a …

Development Of A Counter-Flow Thermal Gradient Microfluidic Device, Shayan Davani

Doctoral Dissertations

This work presents a novel counter-flow design for thermal stabilization of microfluidic thermal reactors. In these reactors, precise control of temperature of the liquid sample is achieved by moving the liquid sample through the thermal zones established ideally through the conduction in the solid material of the device. The goal here is to establish a linear thermal distribution when there is no flow and to minimize the temperature change at flow condition. External convection as well as internal flowinduced effects influence the prescribed thermal distribution. The counter-flow thermal gradient device developed in this study is capable of both stabilizing the …

Long-Term, Super-Resolution Imaging Of Amyloid Structures Using Transient Amyloid Binding Microscopy, Tianben Ding, Kevin Spehar, Jan Bieschke, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Amyloid fibrils and tangles are signatures of Alzheimer disease, but nanometer-sized aggregation intermediates are hypothesized to be the structures most toxic to neurons. The structures of these oligomers are too small to be resolved by conventional light microscopy. We have developed a simple and versatile method, called transient amyloid binding (TAB), to image amyloid structures with nanoscale resolution using amyloidophilic dyes, such as Thioflavin T, without the need for covalent labeling or immunostaining of the amyloid protein. Transient binding of ThT molecules to amyloid structures over time generates photon bursts that are used to localize single fluorophores with nanometer precision. …

Harnessing Neurovascular Interaction To Guide Axon Growth., Paul P Partyka, Ying Jin, Julien Bouyer, Angelica Dasilva, George A Godsey, Robert G Nagele, Itzhak Fischer, Peter Galie

Henry M. Rowan College of Engineering Departmental Research

Regulating the intrinsic interactions between blood vessels and nerve cells has the potential to enhance repair and regeneration of the central nervous system. Here, we evaluate the efficacy of aligned microvessels to induce and control directional axon growth from neural progenitor cells in vitro and host axons in a rat spinal cord injury model. Interstitial fluid flow aligned microvessels generated from co-cultures of cerebral-derived endothelial cells and pericytes in a three-dimensional scaffold. The endothelial barrier function was evaluated by immunostaining for tight junction proteins and quantifying the permeability coefficient t (~10−7 cm/s). Addition of neural progenitor cells to the co-culture …

Muscle Atrophy Marker Expression Differs Between Rotary Cell Culture System And Animal Studies, Charles P. Harding, Elizabeth Vargis

Biological Engineering Faculty Publications

Muscular atrophy, defined as the loss of muscle tissue, is a serious issue for immobilized patients on Earth and for humans during spaceflight, where microgravity prevents normal muscle loading. In vitro modeling is an important step in understanding atrophy mechanisms and testing countermeasures before animal trials. The most ideal environment for modeling must be empirically determined to best mimic known responses in vivo. To simulate microgravity conditions, murine C2C12 myoblasts were cultured in a rotary cell culture system (RCCS). Alginate encapsulation was compared against polystyrene microcarrier beads as a substrate for culturing these adherent muscle cells. Changes after culture …

The Effect Of Calcination Rate On The Structure Of Mesoporous Bioactive Glasses, Saidur Rahman, Andrew Mendonca, Adel Alhalawani, Deanna Polintan, Owen M. Clarkin, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Mesoporous bioactive glasses (MBGs) are designed to have high specific surface area. They are formulated by a sol–gel process to formulate the glass followed by calcination. This study evaluates how calcination heating rate influences the porous architecture, and thereby the specific surface area, of MBGs. MBGs of molar ratio 80:15:5 for SiO₂ :CaO:P₂ O 5 were calcined using both low (1 °C/min) and high (20 °C/min) heating rates, termed as L-MBG and H-MBG, respectively. The results obtained from small-angle X-ray diffraction (SAXRD) confirm that the MBGs possess 2D hexagonal (P6mm) spacing groups and wide-angle XRD confirms the amorphicity …

Hard, Soft And Off-The-Shelf Foot Orthoses And Their Effect On The Angle Of The Medial Longitudinal Arch: A Biplane Fluoroscopy Study, Megan E.R. Balsdon, Colin E. Dombroski, Kristen Bushey, Thomas Jenkyn

Mechanical and Materials Engineering Publications

Background: Foot orthoses have proven to be effective for conservative management of various pathologies. Pathologies of the lower limb can be caused by abnormal biomechanics such as abnormal foot structure and alignment, leading to inadequate support. Objectives: To compare biomechanical effects of different foot orthoses on the medial longitudinal arch (MLA) during dynamic gait using skeletal kinematics. Study Design: Prospective, cross-sectional study design. Methods: The MLA angle was measured for 12 participants among three groups: pes planus, pes cavus and normal arch. Five conditions were compared: three orthotic devices (hard custom foot orthosis (CFO), soft CFO, and off-the-shelf Barefoot Science©), …

Metabolomics Of Sorghum Roots During Nitrogen Stress Reveals Compromised Metabolic Capacity For Salicylic Acid Biosynthesis, Amy M. Sheflin, Dawn Chiniquy, Chaohui Yuan, Emily Goren, Indrajit Kumar, Max Braud, Thomas Brutnell, Andrea L. Eveland, Susannah Tringe, Peng Liu, Stephen Kresovich, Ellen Marsh, Daniel P. Schachtman, Jessica E. Prenni

Nebraska Center for Biotechnology: Faculty and Staff Publications

Sorghum (Sorghum bicolor [L.] Moench) is the fifth most productive cereal crop worldwide with some hybrids having high biomass yield traits making it promising for sustainable, economical biofuel production. To maximize biofuel feedstock yields, a more complete understanding of metabolic responses to low nitrogen (N) will be useful for incorporation in crop improvement efforts. In this study, 10 diverse sorghum entries (including inbreds and hybrids) were field-grown under low and full N conditions and roots were sampled at two time points for metabolomics and 16S amplicon sequencing. Roots of plants grown under low N showed altered metabolic profiles at …

Obstacles To Translating The Promise Of Nanoparticles Into Viable Amyloid Disease Therapeutics, N. P. Van Der Munnik, M. A. Moss, M. J. Uline

Faculty Publications

Nanoparticles (NPs) constitute a powerful therapeutic platform with exciting prospects as potential inhibitors of amyloid-β (Aβ) aggregation, a process associated with Alzheimer's disease (AD). Researchers have synthesized and tested a large collection of NPs with disparate sizes, shapes, electrostatic properties and surface ligands that evoke a variety of responses on Aβ aggregation. In spite of a decade of research on the NP-Aβ system and many promising experimental results, NPs have failed to progress to any level of clinical trials for AD. A theoretical framework with which to approach this physical system is presented featuring two simple metrics, (1) the extent …

Diagnostic Performance Of Receptor-Specific Surgical Specimen Staining Correlates With Receptor Expression Level, Jasmin M. Schaefer, Connor W. Barth, Scott C. Davis, Summer L. Gibbs

Dartmouth Scholarship

Intraoperative margin assessment is imperative to cancer cure but is a continued challenge to successful surgery. Breast conserving surgery is a relevant example, where a cosmetically improved outcome is gained over mastectomy, but re-excision is required in >25  %   of cases due to positive or closely involved margins. Clinical translation of margin assessment modalities that must directly contact the patient or required administered contrast agents are time consuming and costly to move from bench to bedside. Tumor resections provide a unique surgical opportunity to deploy margin assessment technologies including contrast agents on the resected tissues, substantially shortening the path to …

Electrical System For Bioelectric Impedance Using Ad5933 Impedance Converter, Allison Garcia, Ahmet C. Sabuncu

SMU Journal of Undergraduate Research

Benchtop lab equipment, such as the HP4194A Precision Impedance Analyzer, offer accuracy and functionality but are often expensive and bulky. Although integrated circuits offer less functionality than benchtop equivalents, they can be a cheaper alternative for smaller applications. In this study, the AD5933 Impedance Converter was investigated as a low-cost option for impedance analysis of the bicep brachii. The AD5933 evaluation board was properly calibrated to measure human muscle by using an equivalent parallel circuit consisting of a 5 nF capacitor and a 1 kOhm resistor. Next, the impedance of the bicep was measured using the AD5933 as the experimental …

Dynamic Light Scattering Optical Coherence Tomography To Probe Motion Of Subcellular Scatterers., Nico J J Arezza, Marjan Razani, Michael C Kolios

Medical Biophysics Publications

Optical coherence tomography (OCT) is used to provide anatomical information of biological systems but can also provide functional information by characterizing the motion of intracellular structures. Dynamic light scattering OCT was performed on intact, control MCF-7 breast cancer cells and cells either treated with paclitaxel to induce apoptosis or deprived of nutrients to induce oncosis. Autocorrelations (ACs) of the temporal fluctuations of OCT intensity signals demonstrate a significant decrease in decorrelation time after 24 h in both the paclitaxel-treated and nutrient-deprived cell groups but no significant differences between the two groups. The acquired ACs were then used as input for …

Kinematic Foot Types In Youth With Pes Planovalgus Secondary To Cerebral Palsy, Juliet Amene, Joseph J. Krzak, Karen M. Kruger, Logan Killen, Haluk Altiok, Peter A. Smith, Gerald F. Harris

Biomedical Engineering Faculty Research and Publications

Background

Kinematic variability of the foot and ankle segments exists during ambulation among individuals with pes planovalgus (PPV) secondary to cerebral palsy (CP). Clinicians have previously recognized such variability through classification schemes to identify subgroups of individuals, but have been unable to identify kinematic foot types.

Research question

The purpose of this work was to identify kinematic foot types among children with PPV secondary to CP using 3-dimensional multi-segment foot and ankle kinematics during gait as inputs for principal component analysis (PCA) and K-means cluster analysis.

Methods

In a single assessment session, multi-segment foot and ankle kinematics using the …

Exploring The Effects Of Electrospun Fiber Surface Nanotopography On Neurite Outgrowth And Branching In Neuron Cultures, Anthony R. D'Amato, Devan L. Puhl, Alexis M. Ziemba, Christopher D.L. Johnson, Janneke Doedee, Jonathan Bao, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Three aligned, electro spun fiber scaffolds with unique surface features were created from poly-L-lactic acid (PLLA). Fibers without surface nano topography (smooth fibers), fibers with surface divots (shallow pits), and fibers with surface pits (deeper pits) were fabricated, and fiber alignment, diameter, and density were characterized using scanning electron microscopy (SEM). Whole dorsal root ganglia (DRG) were isolated from rats and placed onto uncoated fibers or fibers coated with laminin. On uncoated fibers, neurite outgrowth was restricted by fibers displaying devoted or pitted nano topography when compared to neurite outgrowth on smooth fibers. However, neurites extending from whole DRG cultured …

Quantifying Proliferative And Surface Marker Heterogeneity In Colony‐Founding Connective Tissue Progenitors And Their Progeny Using Time‐Lapse Microscopy, Edward Kwee, Gerald M. Saidel, Kimerly Powell, Christopher M. Heylman, Cynthia A. Boehm, George F. Muschler

Biomedical Engineering

Connective tissue progenitors (CTPs) are defined as the heterogeneous population of tissue‐resident stem and progenitor cells that are capable of proliferating and differentiating into connective tissue phenotypes. The prevalence and variation in clonal progeny of CTPs can be characterized using a colony formation assay. However, colony assays do not directly assess the characteristics of the colony‐founding CTP. We performed large, field‐of‐view, time‐lapse microscopy to manually track colonies back to the founding cells. Image processing and analysis was used to characterize the colonies and their founding cells. We found that the traditional colony‐forming unit (CFU) assay underestimates the number of founding …

Raman Spectroscopy As A Predictive Tool For Monitoring Osteoporosis Therapy In A Rat Model Of Postmenopausal Osteoporosis, J. Renwick Beattie, Antonia Sophocleous, M. Clare Caraher, Olive O'Driscoll, Niamh M. Cummins, Steven E.J. Bell, Mark R. Towler, Alireza Rahimnejad Yazdi, Stuart H. Ralston, Aymen I. Idris

Chemical and Biochemical Engineering Faculty Research & Creative Works

Pharmacological therapy of osteoporosis reduces bone loss and risk of fracture in patients. Modulation of bone mineral density cannot explain all effects. Other aspects of bone quality affecting fragility and ways to monitor them need to be better understood. Keratinous tissue acts as surrogate marker for bone protein deterioration caused by oestrogen deficiency in rats. Ovariectomised rats were treated with alendronate (ALN), parathyroid hormone (PTH) or estrogen (E2). MicroCT assessed macro structural changes. Raman spectroscopy assessed biochemical changes. Micro CT confirmed that all treatments prevented ovariectomy-induced macro structural bone loss in rats. PTH induced macro structural changes unrelated to ovariectomy. …

A Fast, Linear Boltzmann Transport Equation Solver For Computed Tomography Dose Calculation (Acuros Ctd), Adam Wang, Alexander Maslowski, Todd Wareing, Josh Star-Lack, Taly Gilat-Schmidt

Biomedical Engineering Faculty Research and Publications

Purpose

To improve dose reporting of CT scans, patient‐specific organ doses are highly desired. However, estimating the dose distribution in a fast and accurate manner remains challenging, despite advances in Monte Carlo methods. In this work, we present an alternative method that deterministically solves the linear Boltzmann transport equation (LBTE), which governs the behavior of x‐ray photon transport through an object.

Methods

Our deterministic solver for CT dose (Acuros CTD) is based on the same approach used to estimate scatter in projection images of a CT scan (Acuros CTS). A deterministic method is used to compute photon fluence within the …

Novel Supply Chain And Process Modeling For Cell Therapy Manufacturing And Distribution, Chip White, Ben Wang, Kan Wang, Reid Bishop, Aaron Levine, Brian Liu, Bhavya Divvela, Aubrey Incorvaia, Kris Saha, Tava Das

Advancing Manufacture of Cell and Gene Therapies VI [2019]

We present a two-level hierarchical supply chain model of (autologous) CAR-T cell therapy that serves as the basis for the development of strategies to: 1) deliver cell therapy products that are safe and have a high level of efficacy, 2) minimize fulfillment time and variability, and 3) reduce total manufacturing and logistics costs while reducing the risk of patient morbidity and mortality. The model consists of two integral components: (1) an agent-based program for a “single manufacturing facility” that simulates the manufacturing and quality control process of cell therapy; and (2) a supply chain network program that evaluates different supply …

Key Engineering Challenges In The Biomanufacturing Of Lentiviral Viral Vectors, Peter Jones

Advancing Manufacture of Cell and Gene Therapies VI [2019]

No Abstract.

Tangential Flow Filtration And Scalability In Viral Vector Purification, Eni Sterjanaj, Heather Mall, Rachel Legmann, Jacky Dang

Advancing Manufacture of Cell and Gene Therapies VI [2019]

Pall Biotech has linearly scalable tangential flow filtration technology that can cover processing volume ranges from less than a liter to over 2000 liters. Manual assemblies can be used with Pall TFF filters in scales under 20L and programmable skids are available for larger scales. In this document TFF linear scalability of up to 200 liters is covered starting from a 7L initial volume and maintaining similar pressures, processing times and yields at all scales. Using this scalable technology Pall biotech can help biologics companies go to clinical trials and to commercial scale manufacturing successfully.

Please click Additional Files below …

Conference Program, Dolores Baksh, Rod Rietze, Ivan Wall

Advancing Manufacture of Cell and Gene Therapies VI [2019]

No abstract provided.

Workshop Agenda, Fernanda Masri

Advancing Manufacture of Cell and Gene Therapies VI [2019]

No abstract provided.

Development Of A Closed Car-T Manufacturing Process, Loo-Yong Steven Kee, Calley Hirsch, Devina Ramsaroop, Elizabeth Csaszar, Danylo Sirskyj, Aaron Dulgar-Tulloch

Advancing Manufacture of Cell and Gene Therapies VI [2019]

The field of immunotherapy has emerged as a promising new type of treatment for cancer with the approval of the first two CAR-T therapies. The clinical success of T-cell based immunotherapies necessitates a robust manufacturing process for these products to be consistently produced at commercial scale. Our CAR-T workflow combines unit operation specific solutions for thaw of an apheresis unit, wash, CD3 selection, T-cell activation, lentiviral transduction, incubator- and reactor-based expansion culture, harvest, formulation, cryopreservation and thaw of CAR-T product. We have evaluated the impact of both serum-containing and xeno-free culture media, commercially available T-cell selection and activation reagents, closed …

Scale-Up Study For Ex-Vivo Expansion Of Allogeneic Natural Killer Cells In Stirred-Tank Bioreactor, Juyoung Kim, Hyung Jin Nam, Sang Hyun Lee, Jong Beom Ku, Seung Ryel Han, Hye Jin Shin, Yu Kyeong Hwang, Sang Hoon Paik

Advancing Manufacture of Cell and Gene Therapies VI [2019]

Natural killer (NK) cells are a type of lymphocyte in the blood that are responsible for innate and adaptive immune response, and they mature in the liver and bone marrow. Being a key role in host defense system with direct and indirect killing of virus-infected cells or cancer cells, NK cell has been considered an attractive candidate for cancer therapy. Peripheral blood shows the low frequency of NK cells, so ex vivo expansion method is important to obtain sufficient NK cells for therapeutic use. Currently, we successfully developed bioreactor process for NK cell expansion on lab-scale. Stirred-tank bioreactor could be …

Single Use Disposable Biosettler Removes The Dead Cells And Cell Debris Selectively To Increase The Viability Percentage Of Mammalian Cells (E.G., Car-T) During Expansion, Dhinakar Kompala

Advancing Manufacture of Cell and Gene Therapies VI [2019]

Current challenge in a FDA approved cell therapy product for adult B-cell leukemia is reported to be the percentage of viable cells after manufacturing is sometimes out of specified range. As the head of a large contract development and manufacturing organization observed, this fall in viability percentage during CAR-T cell manufacturing is a challenge to the whole industry.

We present a simple and powerful off-the-shelf solution to this big challenge in all mammalian cell culture expansion bioreactor system. Our single use disposable BioSettler has been demonstrated to be uniquely capable of removing dead cells and cell debris selectively from the …