Engineering Commons^™

A Model Microfluidics-Based System For The Human And Mouse Retina., Shawn Mishra, Ankush Thakur, Stephen Redenti, Maribel Vazquez

Publications and Research

The application of microfluidics technologies to the study of retinal function and response holds great promise for development of new and improved treatments for patients with degenerative retinal diseases. Restoration of vision via retinal transplantation therapy has been severely limited by the low numbers of motile cells observed post transplantation. Using modern soft lithographic techniques, we have developed the μRetina, a novel and convenient biomimetic microfluidics device capable of examing the migratory behavior of retinal lineage cells within biomimetic geometries of the human and mouse retina. Coupled computer simulations and experimental validations were used to characterize and confirm the formation …

Egf As A New Therapeutic Target For Medulloblastoma Metastasis, Jennifer Rico-Varela, Tanya Singh, Sean Mccutcheon, Maribel Vazquez

Publications and Research

Medulloblastoma (MB) is a malignant pediatric brain tumor known for its aggressive metastatic potential. Despite the well-documented migration of MB cells to other parts of the brain and spinal column, MB chemotaxis is poorly understood. Herein, we examined the in vitro migratory and cellular responses of MB-derived cells to external signaling of Epidermal Growth Factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF-BB), and the stromal cellderived factors 1-alpha (SDF-1). Experiments utilized transwell assays and immunocytochemistry to identify receptor activation in MB migration, and used a microfluidic platform to examine directionality, trajectory, and gradient-dependence of motile cells. Data illustrates …

High Throughput Screening Of Priming Candidates For Impact On Nonviral Gene Delivery, Albert L. Nguyen

Department of Biological Systems Engineering: Dissertations and Theses

Priming, in the context of nonviral gene delivery, is the treatment of cells with a compound prior to gene transfer that enhances transfection efficiency and/or transgene expression. Essentially, it is the application of an adjuvant approach to gene delivery. Effective transfection strategies may require priming to compete with the efficiency of viral transduction in order to achieve clinically relevant efficiency and expression in vivo. To search for priming compounds, a high throughput screen of the NIH Clinical Collection was performed using 25kDa b-PEI, an EGFP/luciferase plasmid, and HEK293T cells. The EGFP reporter was multiplexed with Hoechst 33342 and Resazurin fluorescence …

A Collagen Based Tissue Engineered Heart Valve Shows Excellent Functionality And Remodelling After Dynamic Conditioning, Claire Brougham, Ricardo Moreira, Tanya J. Levingstone, Stefan Jockenhoevel, Petra Mela, Fergal J. O'Brien

Conference Papers

No abstract provided.

Effect Of Tendon Vibration On Hemiparetic Arm Stability In Unstable Workspaces, Megan O. Conrad, Bani Gadhoke, Robert A. Scheidt, Brian D. Schmit

Biomedical Engineering Faculty Research and Publications

Sensory stimulation of wrist musculature can enhance stability in the proximal arm and may be a useful therapy aimed at improving arm control post-stroke. Specifically, our prior research indicates tendon vibration can enhance stability during point-to-point arm movements and in tracking tasks. The goal of the present study was to investigate the influence of forearm tendon vibration on endpoint stability, measured at the hand, immediately following forward arm movements in an unstable environment. Both proximal and distal workspaces were tested. Ten hemiparetic stroke subjects and 5 healthy controls made forward arm movements while grasping the handle of a two-joint robotic …

Supervised Machine Learning For Classification Of The Electrophysiological Effects Of Chronotropic Drugs On Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Christopher Heylman, Rupsa Datta, Agua Sobrino, Steven George, Enrico Gratton

Biomedical Engineering

Supervised machine learning can be used to predict which drugs human cardiomyocytes have been exposed to. Using electrophysiological data collected from human cardiomyocytes with known exposure to different drugs, a supervised machine learning algorithm can be trained to recognize and classify cells that have been exposed to an unknown drug. Furthermore, the learning algorithm provides information on the relative contribution of each data parameter to the overall classification. Probabilities and confidence in the accuracy of each classification may also be determined by the algorithm. In this study, the electrophysiological effects of β–adrenergic drugs, propranolol and isoproterenol, on cardiomyocytes derived from …

An Intra-Bone Axial Load Transducer: Development And Validation In An In-Vitro Radius Model, Nikolas K. Knowles, Michael Gladwell, Louis M. Ferreira

Surgery Publications

Background

Accurate measurement of forces through the proximal radius can assess the effects of some surgical procedures on radioulnar load sharing, but is difficult to achieve given the redundant loading nature of the musculoskeletal system. Previously reported devices have relied on indirect measurements that may alter articular joint location and function. An axial load transducer interposed in the diaphysis of the radius may accurately quantify unknown axial loads of the proximal radius, and maintain articular location.

Methods

An in-vitro radius model was developed by interposing an axial load transducer in the diaphysis of the proximal radius. Static loads of 20, …

Phospho1 Deficiency Transiently Modifies Bone Architecture Yet Produces Consistent Modification In Osteocyte Differentiation And Vascular Porosity With Ageing, Behzad Javaheri, Alessandra Carriero, Katherine Ann Staines, Y.-M. Chang, D. A. Houston, Karla J. Oldknow, José Luis Millán, Bassir N. Kazeruni, Phil L. Salmon, Sandra J. Shefelbine

Biomedical Engineering and Sciences Faculty Publications

PHOSPHO1 is one of principal proteins involved in initiating bone matrix mineralisation. Recent studies have found that Phospho1 KO mice ( Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis. These analyses have however been limited to young mice and it remains unclear whether the role of PHOSPHO1 is conserved in the mature murine skeleton where bone turnover is limited. In this study, we have used ex-vivo computerised tomography to examine the effect of Phospho1 deletion on tibial bone architecture in mice at a range of ages (5, 7, 16 and 34. weeks of age) …

The Effect Of Recency To Human Mobility, Hugo Barbosa, Fernando B. De Lima-Neto, Alexandre Evsukoff, Ronaldo Menezes

Biomedical Engineering and Sciences Faculty Publications

In recent years, we have seen scientists attempt to model and explain human dynamics and in particular human movement. Many aspects of our complex life are affected by human movement such as disease spread and epidemics modeling, city planning, wireless network development, and disaster relief, to name a few. Given the myriad of applications, it is clear that a complete understanding of how people move in space can lead to considerable benefits to our society. In most of the recent works, scientists have focused on the idea that people movements are biased towards frequently-visited locations. According to them, human movement …

Background Differences In Baseline And Stimulated Mmp Levels Influence Abdominal Aortic Aneurysm Susceptibility, Matthew A. Dale, Melissa K. Suh, Shijia Zhao, Trevor Meisinger, Linxia Gu, Vicki J. Swier, Devendra K. Agrawal, Timothy Greiner, Jeffrey S. Carson, B. Timothy Baxter, Wanfen Xiong

Department of Mechanical and Materials Engineering: Faculty Publications

Objective: Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression.

Methods: Mice of C57Bl/6 or 129/SvEv background underwent AAA induction …

When 1 + 1 > 2: Nanostructured Composites For Hard Tissue Engineering Applications, Vuk Uskoković

Pharmacy Faculty Articles and Research

Multicomponent, synergistic and multifunctional nanostructures have taken over the spotlight in the realm of biomedical nanotechnologies. The most prospective materials for bone regeneration today are almost exclusively composites comprising two or more components that compensate for the shortcomings of each one of them alone. This is quite natural in view of the fact that all hard tissues in the human body, except perhaps the tooth enamel, are composite nanostructures. This review article highlights some of the most prospective breakthroughs made in this research direction, with the hard tissues in main focus being those comprising bone, tooth cementum, dentin and enamel. …

Feasibility Of Using Raman-Based Techniques For Breast Cancer Detection, Sara Mollamohammada

Department of Civil and Environmental Engineering: Dissertations, Theses, and Student Research

Breast cancer is one of the common types of cancer among women all over the world. Early diagnosis is an effective way that improve the treatment process and gives the patients a better chance of survival. Many of the patients infected by breast cancer choose breast conservation surgery (BCS). However, some of those will be subjected to mastectomy, and many will have tumor recurrence as there is no precise technique to show the tumor margins. Raman-based methods are powerful techniques with potential to rapidly differentiate normal from tumor tissues and provides a solution to detect tumor margin. This is because …

Increased Lower Limb Spasticity But Not Strength Or Function Following A Single-Dose Serotonin Reuptake Inhibitor In Chronic Stroke, Krishnaj Gourab, Brian D. Schmit, T. George Hornby

Biomedical Engineering Faculty Research and Publications

Objective: To investigate the effects of single doses of a selective serotonin reuptake inhibitor (SSRI) on lower limb voluntary and reflex function in individuals with chronic stroke.

Design: Double-blind, randomized, placebo-controlled crossover trial.

Setting: Outpatient research setting.

Participants: Individuals (N=10; 7 men; mean age ± SD, 57±10y) with poststroke hemiplegia of >1 year duration who completed all assessments.

Interventions: Patients were assessed before and 5 hours after single-dose, overencapsulated 10-mg doses of escitalopram (SSRI) or placebo, with 1 week between conditions.

Main Outcome Measures: Primary assessments included maximal ankle and knee isometric strength, and velocity-dependent (30°/s–120°/s) plantarflexor stretch reflexes under …

Retinal Architecture In ​Rgs9- And ​R9ap-Associated Retinal Dysfunction (Bradyopsia), Rupert W. Strauss, Adam M. Dubis, Robert F. Cooper, Rola Ba-Abbad, Anthony T. Moore, Andrew R. Webster, Alfredo Dubra, Joseph Carroll, Michel Michaelides

Biomedical Engineering Faculty Research and Publications

Purpose

To characterize photoreceptor structure and mosaic integrity in subjects with RGS9- and R9AP-associated retinal dysfunction (bradyopsia) and compare to previous observations in other cone dysfunction disorders such as oligocone trichromacy.

Design

Observational case series.

Methods

setting: Moorfields Eye Hospital (United Kingdom) and Medical College Wisconsin (USA). study population: Six eyes of 3 subjects with disease-causing variants in RGS9 or R9AP. main outcome measures: Detailed retinal imaging using spectral-domain optical coherence tomography and confocal adaptive-optics scanning light ophthalmoscopy.

Results

Cone density at 100 μm from foveal center ranged from 123 132 cones/mm²to 140 013 cones/mm^{2 …}

Improved Sensitivity To Fluorescence For Cancer Detection In Wide-Field Image-Guided Neurosurgery, Michael Jermyn, Yoann Gosselin, Pablo A. Valdes, Mira Sibai, Kolbein Kolste

Dartmouth Scholarship

In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX …

Calibration And Optimization Of 3d Digital Breast Tomosynthesis Guided Near Infrared Spectral Tomography, Kelly E. Michaelsen, Venkataramanan Krishnaswamy, Linxi Shi, Srinivasan Vedantham, Steven Poplack, Andrew Karellas, Brian Pogue, Keith Paulsen

Dartmouth Scholarship

Calibration of a three-dimensional multimodal digital breast tomosynthesis (DBT) x-ray and non-fiber based near infrared spectral tomography (NIRST) system is challenging but essential for clinical studies. Phantom imaging results yielded linear contrast recovery of total hemoglobin (HbT) concentration for cylindrical inclusions of 15 mm, 10 mm and 7 mm with a 3.5% decrease in the HbT estimate for each 1 cm increase in inclusion depth. A clinical exam of a patient's breast containing both benign and malignant lesions was successfully imaged, with greater HbT was found in the malignancy relative to the benign abnormality and fibroglandular regions (11 μM vs. …

The Development Of A Novel Polymer Based System For Gene Delivery, Anh Van Le

FIU Electronic Theses and Dissertations

Gene therapy involves the use of nucleic acids, either DNA or RNA for the treatment, cure, or prevention of human diseases. Synthetic cationic polymers are promising as a tool for gene delivery because of their high level of design flexibility for biomaterial construction and are capable of binding and condensing DNA through electrostatic interactions.

Our lab has developed a novel polymer (poly (polyethylene glycol-dodecanoate) (PEGD), a polyester of polyethylene glycol (PEG) and dodecanedioic acid (DDA). PEGD is a linear viscous polymer that self-assembles into a vesicle upon immersion in an aqueous solution. A copolymer of dodecanedioc acid and polyethylene glycol …

Cobalt Ferrite Nanoparticles Fabricated Via Co-Precipitation In Air: Overview Of Size Control And Magnetic Properties, Dennis Toledo

FIU Electronic Theses and Dissertations

Cobalt Ferrite has important, size-dependent magnetic properties. Consequently, an overview of particle size is important. Co-precipitation in air was the fabrication method used because it is comparatively simple and safe. The effects of three different reaction times including 1, 2, 3 hour(s) on particle size were compared. Also, the effectiveness of three different capping agents (Oleic Acid, Polyvinylpyrollidone (PVP), and Trisodium Citrate) in reducing aggregation and correspondingly particle size were examined. Using Welch’s analysis of variance (ANOVA) and the relevant post hoc tests, there was no significant difference (p=0.05) between reaction times of 1 hour and 2 hours, but there …

Enhanced Flexible Materials For Valve Prosthesis Applications, Makensley Lordeus

FIU Electronic Theses and Dissertations

While mechanical, homograft and bio-prosthetic valves have been used in patients for many decades and have made significant improvements in patient morbidity, there is still a distinct need to overcome their limitations. Recently, emerging elastomer heart valves have been shown to be able to better re-create the flow physics of native heart valves, resulting in preferable hemodynamic responses. Unfortunately, elastomers such as silicone are prone to structural failure, which drastically limits their applicability towards the development of valve prosthesis. In order to produce a mechanically more robust silicone substrate, we reinforced it with graphene nanoplatelets (GNPs). Cytotoxicity and hemocompatibility tests …

Histological Characterization Of Inter Ictal Epileptiform Discharges Generating Brain Regions Using A Preclinical Model Of Focal Cortical Dysplasia, Abhay S. Deshmukh

FIU Electronic Theses and Dissertations

Current clinical practice of resective surgery in focal epilepsy involves electroencephalogram (EEG) brain source imaging to localize irritative brain areas from where Inter-ictal epileptiform discharges (IEDs) emerge, useful to localize the seizures-onset zones. Unfortunately, there are no previous systematic studies to characterize the pathophysiological mechanisms and abnormal cellular substrates in these irritative areas since histological data are available only from the final resective zones. To address this issue we applied a combination of EEG brain imaging described by Bae et al. (2015) using cutting-edge technology for high-density scalp EEG in rodents and histological analysis on a chronic rat model of …

Cellular Events Under Flow States Pertinent To Heart Valve Function, Glenda L. Castellanos

FIU Electronic Theses and Dissertations

Heart valve disease (HVD) or a damaged valve can severely compromise the heart's ability to pump efficiently. Balloon valvuloplasty is preferred on neonates with aortic valve stenosis. Even though this procedure decreases the gradient pressure across the aortic valve, restenosis is observed soon after balloon intervention. Tissue engineering heart valves (TEHV), using bone marrow stem cells (BMSCs) and biodegradable scaffolds, have been investigated as an alternative to current non-viable prosthesis. By observing the changes in hemodynamics following balloon aortic valvuloplasty, we could uncover a potential cause for rapid restenosis after balloon intervention. Subsequently, a tissue engineering treatment strategy based on …

Leveraging Large Data Sets In Continuous Chromatography Applications: Monitoring Critical Process Parameters Using Mvda, Engin Ayturk

Integrated Continuous Biomanufacturing II

Continuous multicolumn chromatography is gaining momentum in the industry as an enabling technology to establish continuous biomanufacturing platforms for monoclonal antibodies and recombinant proteins. Some companies are exploring continuous multicolumn chromatography processes as a stand-alone unit operation to improve specific productivity and/or reduce buffer consumption, while other companies are considering an integrated continuous downstream process based on continuous multicolumn chromatography.

One of the key features of continuous multicolumn chromatography is the amount of data generated during a single manufacturing batch or campaign. Traditional chromatography processes typically yield one (or a few) elution peaks per batch. Continuous chromatography processes, on the …

2d Cine Dense With Low Encoding Frequencies Accurately Quantifies Cardiac Mechanics With Improved Image Characteristics, Gregory J. Wehner, Jonathan D. Grabau, Jonathan D. Suever, Christopher M. Haggerty, Linyuan Jing, David Powell, Sean M. Hamlet, Moriel H. Vandsburger, Xiaodong Zhong, Brandon K. Fornwalt

Biomedical Engineering Faculty Publications

BACKGROUND: Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. The encoding frequency (k_e) maps the measured phase to tissue displacement while the strength of the encoding gradients affects image quality. 2D cine DENSE studies have used a k_e of 0.10 cycles/mm, which is high enough to remove an artifact-generating echo from k-space, provide high sensitivity to tissue displacements, and dephase the blood pool. However, through-plane dephasing can remove the unwanted echo and dephase the blood pool without relying on high k_e. Additionally, the high sensitivity comes …

Regulatory Challenges Of Continuous Biomanufacturing, Andy Papas

Integrated Continuous Biomanufacturing II

The interaction with regulatory agencies on the biomanufacturing of therapeutic proteins, mAbs, or other large molecules occurs throughout the drug development of the biologic; it begins with the original IND, accelerates at the licensing phase and continues throughout the product’s life cycle. There are many regulatory challenges along this journey.

Because of uniqueness of continuous biomanufacturing, one challenge that occurs throughout the product’s lifecycle is the inevitable change in Agency product reviewers who many times need to be educated on the nuances of your process or have a different opinion or expectation on how things should be done. As such, …

Pat Concepts For Chromatography: Real-Time Monitoring, Real-Time Control, And Cause Of Error Diagnostics, Nina Brestrich, Tobias Hahn, Adrian Sanden, Till Briskot, Jurgen Hubbuch

Integrated Continuous Biomanufacturing II

In the recent years, the growing competition in the biopharmaceutical industry due to biosimilars combined with market fluctuations and increasing product pipelines have given rise to the evaluation of continuous processing. Advantages include smaller equipment that may be disposable, an overall process intensification as well as steady-state operation. As variability should be managed by the continuous process itself to insure a consistent product quality, the development of advanced Process Analytical Technology (PAT) concepts is one crucial aspect for the implementation of continuous processing.

In chromatographic protein purification, process variability can lead to variations in retention volumes or peak shapes of …

Cder's Emerging Technology Team, Kurt Brorson, Sau Lee

Integrated Continuous Biomanufacturing II

The newly formed Emerging Technology Team (ETT) draws membership from all CDER quality review, research and inspection functions, including Office of Biotechnology Products. The goal of the ETT is provide a primary point of contact for external inquiries regarding emerging technology in pharmaceutical and biotechnology manufacturing and quality control. The ETT will partner with review offices in a cross-functional manner and identify regulatory strategy and resolve roadblocks to new technologies relating to existing guidance, policy or practices related to review or inspection. The ETT’s initial focus will be innovation on novel products, manufacturing processes, or testing technologies or processes to …

Monitoring And Control Of Reproducibility In Quasi-Continuous Integrated Production Processes Of Active Pharmaceutical Ingredients, Reiner Luttman, Sven Oliver Borchert, Jan Patrick Voss, Gesine Cornelissen

Integrated Continuous Biomanufacturing II

The development of integrated production processes include the combination and transformation of current batch oriented unit operations into linked sequential/parallel production strategies.

The presented process starts with a two-stage upstream consisting of cell cultivation and subsequent protein production, which in turn results in a five step downstream process, consisting of cell clarification via a separator, retention of cellular debris using microfiltration, concentration of the secreted product by ultrafiltration with subsequent buffer exchange through diafiltration, followed by a final purification using column chromatography.

The three main operations cell breeding, protein production and the complete downstream line are running in series, but …

Dynamic Oncolytic Measles Virus Production, Tanja Grein, Denise Salzig, Michael Muehlebach, Peter Czermak

Integrated Continuous Biomanufacturing II

Oncolytic viruses can be effective weapons against cancer with few treatment options. For example the tissue culture–adapted Edmonston strains of measles virus (MV) have altered its receptor specificity and became selectively oncolytic with attenuated pathogenicity. Russel et al. showed in 2014 full remission in an advanced stage multiple myeloma patient after systemic application of genetically modified MV. In this clinical trial, the patient was treated by intravenous infusion of 10¹¹ TCID₅₀ (50% tissue culture infectious dose) - of an engineered MV encoding human sodium iodide symporter. Appropriate medical treatment with oncolytic viruses calls for high concentrations and absolute …

Transforming The Present Into The Future With Uncertainty And Imprecision, Chales Cooney

Integrated Continuous Biomanufacturing II

No abstract provided.

How Continuous-Like Processes Improve Affordability For Viral Vaccines - Example Of Laiv, Jose Castillo

Integrated Continuous Biomanufacturing II

Designing a continuous process for a life viral vaccine could be seen useless, and challenging, as the virus infection will kill the cell substrate after 2-5 days of infection.

From the technical perspective, chaining the operations of cell culture under perfusion and viral production, clarification and capture / concentration is an efficient option to setup a small scale continuous automated process to manufacture massive amounts of viral vaccines.

We will show how beneficial it can be in terms of process development, manufacturing simplicity, capital expenditure and cost of production. Also, we will show how this approach can help producers of …