Biomedical Engineering and Bioengineering Commons^™

6d Single-Fluorogen Orientation-Localization Microscopy For Elucidating The Architecture Of Beta-Sheet Assemblies And Biomolecular Condensates, Tingting Wu, Weiyan Zhou, Jai S. Rudra, Rohit V. Pappu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

We develop six-dimensional single-molecule orientation-localization microscopy (SMOLM) to measure the 3D positions and 3D orientations simultaneously of single fluorophores. We show how careful optimization of phase and polarization modulation components can encode phase, polarization, and angular spectrum information from each fluorescence photon into a microscope’s dipole-spread function. We used the transient binding and blinking of Nile red (NR) to characterize the helical structure of fibrils formed by designed amphipathic peptides, KFE8^L and KFE8^D, and the pathological amyloid-beta peptide Aβ42. We also deployed merocyanine 540 to uncover the interfacial architectures of biomolecular condensates.

Six-Dimensional Single-Molecule Imaging With Isotropic Resolution Using A Multi-View Reflector Microscope, Oumeng Zhang, Zijian Guo, Yuanyuan He, Tingting Wu, Michael D. Vahey, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Imaging of both the positions and orientations of single fluorophores, termed single-molecule orientation-localization microscopy, is a powerful tool for the study of biochemical processes. However, the limited photon budget associated with single-molecule fluorescence makes high-dimensional imaging with isotropic, nanoscale spatial resolution a formidable challenge. Here we realize a radially and azimuthally polarized multi-view reflector (raMVR) microscope for the imaging of the three-dimensional (3D) positions and 3D orientations of single molecules, with precisions of 10.9 nm and 2.0° over a 1.5-μm depth range. The raMVR microscope achieves 6D super-resolution imaging of Nile red molecules transiently bound to lipid-coated spheres, accurately resolving …

Understanding The Role Of Antioxidant Nanoparticles In Improving The Outcome Of Secondary Injury In Traumatic Brain Injury, Aria W. Tarudji

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Following traumatic brain injury (TBI), excess reactive oxygen species (ROS) and other free radicals are released, inducing the cascade of secondary injury that exacerbate the outcomes of TBI. Antioxidant nanoparticles (ANPs) have shown promising outcomes in reducing the progression of TBI, which may be due to the higher accumulation and retention of ANPs in the injured brain. However, there is limited knowledge of: 1) antioxidant activities needed in TBI treatment, 2) correlation between longer retention, bioavailability, and target engagement with antioxidant treatments, and 3) sexual dimorphism to ANP treatments.

This dissertation assesses multiple ANPs with various scavenging activities and durations …

Biomedical Applications Of Lanthanide Nanomaterials, For Imaging, Sensing And Therapy, Qize Zhang, Stephen O'Brien, Jan Grimm

Publications and Research

The application of nanomaterials made of rare earth elements within biomedical sciences continues to make significant progress. The rare earth elements, also called the lanthanides, play an essential role in modern life through materials and electronics. As we learn more about their utility, function, and underlying physics, we can contemplate extending their applications to biomedicine. This particularly applies to diagnosis and radiation therapy due to their relatively unique features, such as an ultra-wide Stokes shift in the luminescence, variable magnetism and potentially tunable properties, due to the library of lanthanides available and their multivalent oxidation state chemistry. The ability to …

Flexible Battery-Less Wireless Glucose Monitoring System, Saikat Banerjee, Gymama Slaughter

Bioelectrics Publications

In this work, a low power microcontroller-based near field communication (NFC) interfaced with a flexible abiotic glucose hybrid fuel cell is designed to function as a battery-less glucose sensor. The abiotic glucose fuel cell is fabricated by depositing colloidal platinum (co–Pt) on the anodic region and silver oxide nanoparticles-multiwalled carbon nanotubes (Ag₂O-MWCNTs) composite on the cathodic region. The electrochemical behavior is characterized using cyclic voltammetry and chronoamperometry. This glucose hybrid fuel cell generated an open circuit voltage of 0.46 V, short circuit current density of 0.444 mA/cm2, and maximum power density of 0.062 mW/cm² at 0.26 V …

Impact Of Angiogenic And Osteogenic Factors In The Presence Of Biodegradable Piezoelectric Films, Jayla Millender

Honors Scholar Theses

One of the most common causes of bone graft rejection is lack of a vascular network connecting the graft to the existing native tissue – allowing for nutrient flow. Under current grafting techniques, the existing blood vessel network in the patient slowly invades the implant in order to supply the injured site with its necessary nutrients. The purpose of this research is to determine if a synthetic bone graft with a stable microvascular network can be developed in vitro. I hypothesize that the use of indirect angiogenic factors such as sonic hedgehog homolog and hypoxia-inducible factor-1 in combination with the …

Discharge Mode Transition In He/Ar Atmospheric Pressure Plasma Jet And Its Inactivation Effect Against Tumor Cells In Vitro, Bolun Pang, Zhijie Liu, Sitao Wang, Yuting Gao, Huaiyan Zhang, Feng Zhang, Xiamin Tantai, Dehui Xu, Dingxin Liu, Michael G. Kong

Bioelectrics Publications

Discharge characteristic comparisons between He and Ar plasma jets have been extensively reported, but is rarely reported for the comprehensive study of discharge mode transition from He jet to Ar jet, especially its induced liquid chemistry and biological effect. In this paper, we investigate the plasma jet mode transformation by varying the Ar contents in the He/Ar mixing working gas, particularly focusing on the effect of liquid chemistry of plasma activated water (PAW) and the corresponding inactivation effect against tumor cells in vitro. The mode transition process from He jet to Ar jet is characterized by the discharge images, …

3-D Fabry–Pérot Cavities Sculpted On Fiber Tips Using A Multiphoton Polymerization Process, Jonathan W. Smith, Jeremiah C. Williams, Joseph S. Suelzer, Nicholas G. Usechak, Hengky Chandrahalim

Faculty Publications

This paper presents 3-D Fabry–Pérot (FP) cavities fabricated directly onto cleaved ends of low-loss optical fibers by a two-photon polymerization (2PP) process. This fabrication technique is quick, simple, and inexpensive compared to planar microfabrication processes, which enables rapid prototyping and the ability to adapt to new requirements. These devices also utilize true 3-D design freedom, facilitating the realization of microscale optical elements with challenging geometries. Three different device types were fabricated and evaluated: an unreleased single-cavity device, a released dual-cavity device, and a released hemispherical mirror dual-cavity device. Each iteration improved the quality of the FP cavity's reflection spectrum. The …

Engineering Electromagnetic Systems For Next-Generation Brain-Machine Interface, Brayan Ricardo Navarrete

FIU Electronic Theses and Dissertations

MagnetoElectric Nanoparticles (MENPs) are known to be a powerful tool for a broad range of applications spanning from medicine to energy-efficient electronics. MENPs allow to couple intrinsic electric fields in the nervous system with externally controlled magnetic fields. This thesis exploited MENPs to achieve contactless brain-machine interface (BMIs). Special electromagnetic devices were engineered for controlling the MENPs’ magnetoelectric effect to enable stimulation and recording. The most important engineering breakthroughs of the study are summarized below.

(I) Metastable Physics to Localize Nanoparticles: One of the main challenges is to localize the nanoparticles at any selected site(s) in the brain. The fundamental …

Probing Nanoelectroporation And Resealing Of The Cell Membrane By The Entry Of Ca2+ And Ba2+ Ions, Wenfei Bo, Mantas Silkunas, Uma Mangalanathan, Vitalij Novickij, Maura Casciola, Iurii Semenov, Shu Xiao, Olga N. Pakhomova, Andrei G. Pakhomov

Bioelectrics Publications

The principal bioeffect of the nanosecond pulsed electric field (nsPEF) is a lasting cell membrane permeabilization, which is often attributed to the formation of nanometer-sized pores. Such pores may be too small for detection by the uptake of fluorescent dyes. We tested if Ca²⁺, Cd²⁺, Zn²⁺, and Ba²⁺ ions can be used as nanoporation markers. Time-lapse imaging was performed in CHO, BPAE, and HEK cells loaded with Fluo-4, Calbryte, or Fluo-8 dyes. Ca²⁺ and Ba²⁺ did not change fluorescence in intact cells, whereas their entry after nsPEF increased fluorescence within <1 ms. The threshold for one 300-ns pulse was at 1.5–2 kV/cm, much lower than >7 …

Label-Free Microrna Optical Biosensors, Meimei Lai, Gymama Slaughter

Bioelectrics Publications

MicroRNAs (miRNAs) play crucial roles in regulating gene expression. Many studies show that miRNAs have been linked to almost all kinds of disease. In addition, miRNAs are well preserved in a variety of specimens, thereby making them ideal biomarkers for biosensing applications when compared to traditional protein biomarkers. Conventional biosensors for miRNA require fluorescent labeling, which is complicated, time-consuming, laborious, costly, and exhibits low sensitivity. The detection of miRNA remains a big challenge due to their intrinsic properties such as small sizes, low abundance, and high sequence similarity. A label-free biosensor can simplify the assay and enable the direct detection …

The Modeling, Design, Fabrication, And Application Of Biosensor Based On Electric Cell-Substrate Impedance Sensing (Ecis) Technique In Environmental Monitoring, Xudong Zhang, William Wang, Sunghoon Jang

Publications and Research

In this research, the modeling, design, fabrication, and application of ECIS sensors in environmental monitoringare studied. The ECIS sensors are able to qualify the water toxicity through measuring the cell impedance. A novel mathematical model is proposed to analyze the distribution of electric potential and current of ECIS. This mathematical model is validated by experimental data and can be used to optimize the dimension of ECIS electrodes in order to satisfy environmental monitors. The detection sensitivity of ECIS sensors is analyzed by the mathematical model and experimental data. The simulated and experimental results show that ECIS sensors with smaller radius …

Titanium Nitride Nanotube Electrode, Gui Chen, Marcella Gatti

Research Opportunities for Engineering Undergraduates (ROEU) Program 2018-19

This project presents a corrosion-resistant and high capacity implantable TiN nanotube electrode to work as a neural probe. Smaller electrode size allows for reduced tissue damage while the nanopore morphology of the TiN gives a larger surface area and stability to the electrode. The electrode offers improved biocompatibility, reduced tissue damage, reduced cost, and increased usability over time.

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the …

Eigenstrain As A Mechanical Set-Point Of Cells, Shengmao Lin, Marsha C. Lampi, Cynthia A. Reinhart-King, Gary C.P. Tsui, Jian Wang, Carl A. Nelson, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

Cell contraction regulates how cells sense their mechanical environment. We sought to identify the set-point of cell contraction, also referred to as tensional homeostasis. In this work, bovine aortic endothelial cells (BAECs), cultured on substrates with different stiffness, were characterized using traction force microscopy (TFM). Numerical models were developed to provide insights into the mechanics of cell–substrate interactions. Cell contraction was modeled as eigenstrain which could induce isometric cell contraction without external forces. The predicted traction stresses matched well with TFM measurements. Furthermore, our numerical model provided cell stress and displacement maps for inspecting the fundamental regulating mechanism of cell …

Method And Shear-Driven Micro-Fluidic Pump, Nihad E. Daidzic

Aviation Department Publications

United States Patent Application, Publication Number US 2017/0096990 A1, Publication Date April 6, 2017.

An example includes an apparatus to pump a fluid. The apparatus includes a housing extending along a length defining an elongate interior, an actuator in the housing, conforming to the elongate interior, the actuator including a plurality of lumens, each having a length extending substantially parallel to the elongate interior, each from around 10 to 200 micrometers across and an actuator configured to oscillate the actuator in the actuator housing along the length of the elongate interior with a rate differential between movement in a first …

Shear Driven Micro-Fluidic Pump, Nihad E. Daidzic

Aviation Department Publications

United States Patent, Patent Number US 9,528,503 B2, Date of Patent December 27, 2016.

An example includes an apparatus to pump a fluid. The apparatus includes a housing extending along a length defining an elongate interior, an actuator in the housing, conforming to the elongate interior, the actuator including a plurality of lumens, each having a length extending substantially parallel to the elongate interior, each from around 10 to 200 micrometers across and an actuator configured to oscillate the actuator in the actuator houslng along the length of the elongate interior with a rate differential between movement in a first …

Characterization Of Molecular Communication Based On Cell Metabolism Through Mutual Information And Flux Balance Analysis, Zahmeeth Sayed Sakkaff

Department of Computer Science and Engineering: Dissertations, Theses, and Student Research

Synthetic biology is providing novel tools to engineer cells and access the basis of their molecular information processing, including their communication channels based on chemical reactions and molecule exchange. Molecular communication is a discipline in communication engineering that studies these types of communications and ways to exploit them for novel purposes, such as the development of ubiquitous and heterogeneous communication networks to interconnect biological cells with nano and biotechnology-enabled devices, i.e., the Internet of Bio-Nano Things. One major problem in realizing these goals stands in the development of reliable techniques to control the engineered cells and their behavior from the …

Hydrothermally Processed 1d Hydroxyapatite: Mechanism Of Formation And Biocompatibility Studies, Zoran Stojanović, Nenad Ignjatović, Victoria M. Wu, Vojca Žunič, Ljiljana Veselinović, Srečo D. Škapin, Miroslav Miljković, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome …

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …

Molecular Combing Of Dna Nanofibers And Comparison To Electrospinning, Tanner L. Buresh

UCARE Research Products

The goal of these experiments was to create DNA nanofibers through the method of molecular combing (MC) and then compare the MC fibers to fibers created with electrospinning (ES). The experiment was designed and initial samples were created. After confirming that the method would succeed in creating DNA fibers, several parametric studies were performed in order to optimize the experiment and create the most uniform fibers possible. The parametric studies were done on the following variables: substrate material, pH level of DNA solution, and DNA solution concentration. After completion of all experiments, it was determined that although fibers could be …

Expanded 3d Nanofiber Scaffolds: Cell Penetration, Neovascularization, And Host Response, Jiang Jiang, Zhuoran Li, Hongjun Wang, Yue Wang, Mark A. Carlson, Matthew J. Teusink, Matthew R. Macewan, Linxia Gu, Jingwei Xie

Department of Mechanical and Materials Engineering: Faculty Publications

Herein, a robust method to fabricate expanded nanofiber scaffolds with controlled size and thickness using a customized mold during the modified gas-foaming process is reported. The expansion of nanofiber membranes is also simulated using a computational fluid model. Expanded nanofiber scaffolds implanted subcutaneously in rats show cellular infiltration, whereas non-expanded scaffolds only have surface cellular attachment. Compared to unexpanded nanofiber scaffolds, more CD68+ and CD163+ cells are observed within expanded scaffolds at all tested time points post-implantation. More CCR7+ cells appear within expanded scaffolds at week 8 post-implantation. In addition, new blood vessels are present within the expanded scaffolds at …

Protein-Targeted Corona Phase Molecular Recognition, Gili Bisker, Juyao Dong, Hoyoung D. Park, Nicole M. Iverson, Jiyoung Ahn, Justin T. Nelson, Markita P. Landry, Sebastian Kruss, Michael S. Strano

Biological Systems Engineering: Papers and Publications

Corona phase molecular recognition (CoPhMoRe) uses a heteropolymer adsorbed onto and templated by a nanoparticle surface to recognize a specific target analyte. This method has not yet been extended to macromolecular analytes, including proteins. Herein we develop a variant of a CoPhMoRe screening procedure of single-walled carbon nanotubes (SWCNT) and use it against a panel of human blood proteins, revealing a specific corona phase that recognizes fibrinogen with high selectivity. In response to fibrinogen binding, SWCNT fluorescence decreases by >80% at saturation. Sequential binding of the three fibrinogen nodules is suggested by selective fluorescence quenching by isolated sub-domains and validated …

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. …

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 …

Label-Free Surface-Enhanced Raman Spectroscopy-Linked Immunosensor Assay (Slisa) For Environmental Surveillance, Vinay Bhardwaj

FIU Electronic Theses and Dissertations

The contamination of the environment, accidental or intentional, in particular with chemical toxins such as industrial chemicals and chemical warfare agents has increased public fear. There is a critical requirement for the continuous detection of toxins present at very low levels in the environment. Indeed, some ultra-sensitive analytical techniques already exist, for example chromatography and mass spectroscopy, which are approved by the US Environmental Protection Agency for the detection of toxins. However, these techniques are limited to the detection of known toxins. Cellular expression of genomic and proteomic biomarkers in response to toxins allows monitoring of known as well as …

Effects Of Three Dry Powder Inhalers On Deposition Of Aerosolized Medicine In The Human Oral-Pharyngeal-Laryngeal Regions, Mohammed Ali

Technology Faculty Publications and Presentations

The dry powder inhaler (DPI) is a popular, effective and convenient drug delivery device for inhalation therapy to treat asthma. However, a large quantity (approximately 54%) of inhaled aerosols deposit in the oropharyngeal region. Deposition in this region is undesirable because it provides minimum therapeutic benefits and has adverse localized or systemic side effects. This study reports a method of examining electrostatic charge effects on deposition of three DPI aerosols (Spiriva^™ Handihaler, Advair Diskus^™, and Pulmicort^™ Turbohaler) in a cadaver-based cast of the human oral-pharyngeal-laryngeal (OPL) regions. Experimental aerosols were generated from the three commercially available …

Ablation Of Myocardial Tissue With Nanosecond Pulsed Electric Fields, Fei Xie, Frency Varghese, Andrei G. Pakhomov, Iurii Semenov, Shu Xiao, Jonathan Philpott, Christian Zemlin

Bioelectrics Publications

Background

Ablation of cardiac tissue is an essential tool for the treatment of arrhythmias, particularly of atrial fibrillation, atrial flutter, and ventricular tachycardia. Current ablation technologies suffer from substantial recurrence rates, thermal side effects, and long procedure times. We demonstrate that ablation with nanosecond pulsed electric fields (nsPEFs) can potentially overcome these limitations.

Methods

We used optical mapping to monitor electrical activity in Langendorff-perfused New Zealand rabbit hearts (n = 12). We repeatedly inserted two shock electrodes, spaced 2–4 mm apart, into the ventricles (through the entire wall) and applied nanosecond pulsed electric fields (nsPEF) (5–20 kV/cm, 350 ns duration, …

Low Molecular Weight Glucosamine/L-Lactide Copolymers As Potential Carriers For The Development Of A Sustained Rifampicin Release System: Mycobacterium Smegmatis As A Tuberculosis Model, Jorge Ragusa

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged …

Utilizing Fast Spin Echo Mri To Reduce Image Artifacts And Improve Implant/Tissue Interface Detection In Refractory Parkinson’S Patients With Deep Brain Stimulators, Subhendra N. Sarkar, Pooja R. Sarkar, Efstathios Papavassiliou, Rafael Rojas

Publications and Research

Introduction. In medically refractory Parkinson’s disease (PD) deep-brain stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is important in assessing tissue damage and DBS lead placement accuracy. We wanted to identify which MRI sequence can detectDBS leads with smallest artifactual signal void, allowing better tissue/electrode edge conspicuity.

Methods. Using an IRB approved protocol 8 advanced PDpatientswere imagedwithinMRconditional safety guidelines at lowRF power (SAR ≤ 0.1 W/kg) in coronal plane at 1.5T by various sequences.The image slices were subjectively evaluated for diagnostic quality and the lead contact diameters were compared to identify a sequence least affected by metallic leads.

Results …