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Full-Text Articles in Biomedical Engineering and Bioengineering

Regeneration Of The Ventricular Endocardium Within Acellular Whole Rabbit Hearts Using A Layer-By-Layer Seeding Method, Clayton Lewis Compton May 2018

Regeneration Of The Ventricular Endocardium Within Acellular Whole Rabbit Hearts Using A Layer-By-Layer Seeding Method, Clayton Lewis Compton

All Theses

In the United States, 1 out of every 9 death certificates in 2013 referenced heart failure.1 Despite the outstanding need of treatment options for heart failure, heart transplantation remains the optimal treatment method. However, there is a severe shortage of donor hearts available for transplantation.2 Other available treatment options are not ideal because they do not fully restore function and are associated with creating other complications.3 Thus, there is a need for developing a living tissue engineered whole heart for transplantation to provide an alternative option for patients on the waitlist to receive a donor heart.

Our ...


Autologous Protein Solution Exhibits Potential To Mitigate Osteoarthritis (Oa) Progression In A Human Explant Co-Culture Model, Kathleen Emily Steckbeck Aug 2016

Autologous Protein Solution Exhibits Potential To Mitigate Osteoarthritis (Oa) Progression In A Human Explant Co-Culture Model, Kathleen Emily Steckbeck

All Theses

Osteoarthritis (OA) is a debilitating and painful disease that affects upwards of one in every eight adults1,2. OA influences the entire joint, but is traditionally characterized by cartilage degradation3. OA is a multifactorial disease with genetic, biological, and biochemical consideration, but there has been a recent shift in scientific opinion that the pathological progression of OA stems from an inflammatory milieu produced by the feed-forward progressive pathway as evidenced by simultaneous cartilage and synovium co-culture4–7. Autologous protein solution (APS) poses as an intriguing potential OA therapy by possessing a high anti-inflammatory and anabolic mediator concentration profile that could ...


Low Cost, Carbon-Based Micro- And Nano-Structured Electrodes For High Performance Supercapacitors, Kryssia Pamela Díaz Orellana May 2016

Low Cost, Carbon-Based Micro- And Nano-Structured Electrodes For High Performance Supercapacitors, Kryssia Pamela Díaz Orellana

All Dissertations

Advances in the development of sustainable, low-cost, and reliable energy storage technologies have become a high priority as the demand for high power, and high energy storage devices has risen with emerging technologies in electronics, transportation, and renewable energy systems. Supercapacitors, due to their relatively high energy density and power density, provide an attractive alternative to bridge the gap between conventional batteries and capacitors. Materials ranging from high surface area, inert carbons to Faradaic metal oxides and conducting polymers have been used to achieve a range of performance properties in supercapacitors. However, the development of new technologies faces many challenges ...


Analysis Of Citrate Content In Bone Using High Performance Liquid Chromatography, Matthew Konstantin Pysh Dec 2015

Analysis Of Citrate Content In Bone Using High Performance Liquid Chromatography, Matthew Konstantin Pysh

All Theses

Approximately 1.5 wt. % of bone is comprised of citrate molecules bound to the surface of apatite crystals. Furthermore, 80 to 90% of physiological citrate is contained within bone. Recently, interest in citrate has increased due to the potential of a citrate based method for estimation of postmortem intervals, time since death, of skeletal remains. The broad objective of this research was to develop and validate a High-Performance Liquid Chromatography (HPLC) method for quantitative and qualitative analysis of citrate in bone. An appropriate HPLC column and operating conditions for the detection of citrate were selected and subsequently used to analyze ...


Effects Of Growth Factor Supplementation And Environmental Conditions On Human Adipose-Derived Stem Cell Differentiation Towards Urothelial Lineage, James Turner Dec 2015

Effects Of Growth Factor Supplementation And Environmental Conditions On Human Adipose-Derived Stem Cell Differentiation Towards Urothelial Lineage, James Turner

All Dissertations

In recent years, tissue engineering of the bladder has undergone many technological advances. Autologous urothelial cells have been used in animal models and have shown increased performance for ureteral reconstruction compared to unseeded grafts. However, since patients may lack a reliable source of native urothelial cells due to the nature of their specific bladder disease, autologous cells are not an ideal source clinically, and an alternate cell source must be explored. Adipose derived stem cells (ADSCs) are an attractive cell source for such regenerative medicine applications as they have been extensively studied for their multipotential differentiation, immunosuppressive properties, ease of ...


Decellularized Bovine Nucleus Pulposus As A Biomimetic Scaffold For Intervertebral Disc Regeneration, Christopher Fernandez Dec 2015

Decellularized Bovine Nucleus Pulposus As A Biomimetic Scaffold For Intervertebral Disc Regeneration, Christopher Fernandez

All Theses

Low back pain (LBP) is a significant burden with a lifetime prevalence of 84% and estimated expenditures of $85.9 billion.[1,2] Although LBP is multifactorial; it has been shown that LBP can originate from degenerating intervertebral discs (IVDs); a process which initiates in the nucleus pulposus (NP); a hydrated tissue primarily composed of type 2 collagen and proteoglycan. Current therapies for IVD degeneration (IDD) are palliative and merely delay surgical management. While these procedures may relieve pain temporarily, they fail to address the underlying cause of degeneration and make no attempt to regenerate the effected tissue. Additional concerns ...


Manipulation Of The Electrical Double Layer For Control And Sensing In A Solid State Nanopore, Samuel L. Bearden Aug 2015

Manipulation Of The Electrical Double Layer For Control And Sensing In A Solid State Nanopore, Samuel L. Bearden

All Dissertations

Nanopores have been explored with the goal of achieving non-functionalized, sub-molecular sensors, primarily with the purpose of producing fast, low-cost DNA sequencers. Because of the nanoscale volume within the nanopore structure, it is possible to isolate individual molecular and sub-molecular analytes. Nanopore DNA sequencing has remained elusive due to high noise levels and the challenge of obtaining single-nucleotide resolution. However, the complete electrical double layer within the nanopore is a key feature of fluid-nanopore interaction and has been neglected in previous studies. By exploring interactions with the electrical double layer in various nanopore systems, we characterize the material, electrical, and ...


Assessment Of Bore-Cone Taper Junctions In Explanted Modular Total Hip Replacements, Christine Margaret Stamer May 2015

Assessment Of Bore-Cone Taper Junctions In Explanted Modular Total Hip Replacements, Christine Margaret Stamer

All Theses

For people with chronic hip pain due to arthritis or other conditions, a total hip replacement (THR) is a common procedure used to eliminate the pain. Due to the natural variation in patient anatomy, THR prostheses are becoming increasingly more modular to allow for a more customized initial replacement and for an easier revision if needed in the future. Currently, THR prostheses routinely have modular femoral heads to provide surgeons with intraoperative flexibility. This modularity allows the surgeons to maintain the proper leg length and restore hip biomechanics for the patient and insert the components more easily and precisely. Modular ...


Understanding The Fusion And Maturation Of Tissue Engineered Linear Blood Vessels Using Magnetic Cellular Spheroids, Timothy R. Olsen May 2015

Understanding The Fusion And Maturation Of Tissue Engineered Linear Blood Vessels Using Magnetic Cellular Spheroids, Timothy R. Olsen

All Dissertations

Cellular spheroids are attractive for tissue fabrication due to having precise control over cell and extracellular matrix (ECM) composition, the ability for upscaled production and repeatability, their three-dimensional nature and the fact that spheroids will produce their own ECM over time. A critical process in the fabrication of complex tissue structures with cellular spheroids is related to their fusion and maturation. Tissue fusion is a self-assembly process in which two or more distinct cell populations, or tissues, make contact and coalesce to form a single cohesive structure. Maturation of tissue engineered constructs involves developing the mechanical properties and ECM compositions ...


Endothelialization Using Protein Substrates And Hydrogels For Aortic Valve Applications, Elizabeth A. Fontaine May 2015

Endothelialization Using Protein Substrates And Hydrogels For Aortic Valve Applications, Elizabeth A. Fontaine

All Theses

Aortic valve disease is currently the leading cause of cardiovascular morbidity in the United States.1 In 2003, approximately 290,000 patients required heart valve replacement and that number is estimated to continue to rise as the average age of the population continues to increase.2 However, the current valve replacement options have multiple limitations. Tissue engineering hopes to address these shortcomings by providing a viable valve that more closely mimics the native valve, structurally and functionally.3 An ideal valve replacement should contain endothelial and interstitial cells, with the ability to remodel the extra-cellular matrix. While tissue-engineered heart valves ...


Development Of A Transport System For Advancing Tissue Engineering And Cell Identification, Suzanne Mae Tabbaa Dec 2014

Development Of A Transport System For Advancing Tissue Engineering And Cell Identification, Suzanne Mae Tabbaa

All Dissertations

This work centers on the development of a novel passive transport system for two tissue engineering applications – cell distribution and cell separation. This approach relies on a wicking fiber-based system, derived from the textile field that functions by directing and maintaining transport of cells as well as fluids and biomolecules. This system has the ability to enhance cell movement for both the purpose of cell seeding distribution as well as to isolate specific cell types from heterogeneous cell populations.

The success of spinal fusions and large bone defects is often limited by the decreased surrounding vasculature and the ability of ...


Platform Technologies To Advance Clinically Relevant Tissue Engineered Heart Valve Products, Leslie Neil Sierad Aug 2014

Platform Technologies To Advance Clinically Relevant Tissue Engineered Heart Valve Products, Leslie Neil Sierad

All Dissertations

Diseased heart valves are commonly replaced by mechanical, bioprosthetic, or allograft heart valves. These replacements provide major improvements in cardiac function and quality of life, but have significant limitations and eventually require surgical replacement within 15-20 years. These risks are particularly prominent in pediatric patients and young adults. The field of tissue engineering and regenerative medicine, which combines scaffolds and cells, holds great promise in developing living replacement heart valves that would self-repair and grow in size along with the growing children.

The long-term goal of this project is to generate living, tissue-engineered heart valves from biological scaffolds and autologous ...


Development Of Poly(Lactic Acid)-Poly(Ethylene Glycol) Nanoparticles For The Delivery Of Non- Toxic Drug In Combination Therapy For The Treatment Of Glioblastoma And Neuroblastoma, Olivia Grace Decroes Aug 2014

Development Of Poly(Lactic Acid)-Poly(Ethylene Glycol) Nanoparticles For The Delivery Of Non- Toxic Drug In Combination Therapy For The Treatment Of Glioblastoma And Neuroblastoma, Olivia Grace Decroes

All Theses

Glioblastoma and neuroblastoma are both solid-form tumors. Glioblastomas primarily reside in the brain, while neuroblastomas are found in the sympathetic nervous system. Both glioblastoma and neuroblastoma re classified as orphan diseases, which affect less than 200,000 individuals a year. Over the course of 5 years, 40% of patients diagnosed with neuroblastomas and only 6% of patients diagnosed will glioblastomas will be living.73,74. Glioblastoma and neuroblastoma tumors possess a gene known as MGMT. MGMT is used by tumors as a DNA repair mechanism, which increases the likelihood these tumors will become resistant to traditional drug therapies.28,37 ...


Interstitial Cell Seeding And Dynamic Conditioning Of Aortic Heart Valve Scaffolds, Allison Kennamer Dec 2013

Interstitial Cell Seeding And Dynamic Conditioning Of Aortic Heart Valve Scaffolds, Allison Kennamer

All Theses

In 2011, U.S. Markets for Heart Valve Repair and Replacement Products estimated that roughly four million people in the United States are diagnosed with a heart valve disorder annually. And in the following year, the American Heart Association reported that approximately 35,000 deaths in the US were either directly or indirectly attributed to heart valve disease. Diseases of the heart valve are degenerative in nature and therefore progressively worsen unbeknownst to the patient until symptoms become clinically relevant. By this time, the valve is in such poor condition that complete replacement is often the only effective treatment. Current ...


Identification Of Novel Genes Regulating Elastic Fiber Formation Through Expression Profiling Analysis Of Elastogenic Models, Erin Sproul Dec 2013

Identification Of Novel Genes Regulating Elastic Fiber Formation Through Expression Profiling Analysis Of Elastogenic Models, Erin Sproul

All Dissertations

Background: Particularly important to the mechanical performance of native arterial blood vessels is elastin, an extracellular matrix (ECM) protein deposited by VSMCs in the form of elastic fibers, arranged in concentric lamellae in the media of the vessel wall. In addition to serving as major structural elements of arterial walls, providing extensibility and elastic recoil, elastic fibers also influence vascular cell behaviors. For these reasons tissue engineers are attempting to exploit elastic fiber biology to enhance vascular graft design and patency. Therefore, developing a greater understanding of the molecular mechanisms of elastogenesis may offer opportunities to control elastogenesis in tissue ...


Vascular Nanomedicine: Site Specific Delivery Of Elastin Stabilizing Therapeutics To Damaged Arteries, Aditi Sinha Dec 2013

Vascular Nanomedicine: Site Specific Delivery Of Elastin Stabilizing Therapeutics To Damaged Arteries, Aditi Sinha

All Dissertations

Elastin, a structural protein in the extra-cellular matrix, plays a critical role in the normal functioning of blood vessels. Apart from performing its primary function of providing resilience to arteries, it also plays major role in regulating cell-cell and cell-matrix interactions, response to injury, and morphogenesis. Medial arterial calcification (MAC) and abdominal aortic aneurysm (AAA) are two diseases where the structural and functional integrity of elastin is severely compromised. Although the clinical presentation of MAC and AAA differ, they have one common underlying causative mechanism--pathological degradation of elastin. Hence prevention of elastin degradation in the early stages of MAC and ...


In Vitro Simulation Of Pathological Bone Conditions To Predict Clinical Outcome Of Bone Tissue Engineered Materials, Duong Nguyen Dec 2013

In Vitro Simulation Of Pathological Bone Conditions To Predict Clinical Outcome Of Bone Tissue Engineered Materials, Duong Nguyen

All Dissertations

According to the Centers for Disease Control, the geriatric population of ≥65 years of age will increase to 51.5 million in 2020; 40% of white women and 13% of white men will be at risk for fragility fractures or fractures sustained under normal stress and loading conditions due to bone disease, leading to hospitalization and surgical treatment. Fracture management strategies can be divided into pharmaceutical therapy, surgical intervention, and tissue regeneration for fracture prevention, fracture stabilization, and fracture site regeneration, respectively. However, these strategies fail to accommodate the pathological nature of fragility fractures, leading to unwanted side effects, implant ...


Biological Scaffolds For Peripheral Vascular Surgery, George Fercana Dec 2013

Biological Scaffolds For Peripheral Vascular Surgery, George Fercana

All Dissertations

The gold standards for small diameter peripheral vascular graft replacement are autologous arteries or veins; however, one-third of patients lack such vessels due to previous vessel harvesting or advanced vascular disease. A promising approach for patients in this category is tissue engineering with off-the-shelf biological vascular grafts. Three small diameter acellular scaffolds were developed and evaluated as vascular grafts. Porcine renal arteries (2-3 mm diameter, 20 mm length) were decellularized by immersion and stabilized with penta-galloyl glucose (PGG) with and without subsequent heparinization via carbodiimide chemistry. Bovine mammary (4-6 mm ID, 250 mm length) and femoral arteries (6-8 mm ID ...


Functional Stroke Recovery Through Tissue Engineered Niche Neural Constructs, Natasha Topoluk Dec 2013

Functional Stroke Recovery Through Tissue Engineered Niche Neural Constructs, Natasha Topoluk

All Theses

According to the Centers for Disease Control and Prevention, stroke is statistically responsible for 1 in every 19 deaths of American citizens.5 Stroke is the leading cause of permanent disability due to the fact that it compromises both cellular and tissue components of the brain, leading to the formation of a physical void within the tissue. Current research approaches address the cellular component by injecting stem cells into this void; however, extremely low cell engraftment, high injected cell death, and overall no matrix regeneration are observed. Additionally, these stem cells do not remain committed to a neural lineage. We ...


The Effects Of Different Size Gold Nanoparticles On Mechanical Properties Of Vascular Smooth Muscle Cells Under Mechanical Stretching, Tri Kieu Dec 2013

The Effects Of Different Size Gold Nanoparticles On Mechanical Properties Of Vascular Smooth Muscle Cells Under Mechanical Stretching, Tri Kieu

All Theses

The field of nanotechnology research has seen a large growth in the past few decades due to the great potential of novel nano-size material for useful applications such as drug delivery and medical imaging. Also, they are a promising platform for the detection of terrible diseases such as cancer and atherosclerosis. Although these materials hold great promise, there is very limited understanding about the biological effects of these nanoparticles on normal healthy cells, such as vascular smooth muscle cells (VSMCs). The VSMCs are unique cells due to the two distinct phenotype characteristics it can express: a contractile and a synthetic ...


Engineering Beta-Cell Spheroids For Type 1 Diabetes Treatment, Xiaoyan Liu Dec 2013

Engineering Beta-Cell Spheroids For Type 1 Diabetes Treatment, Xiaoyan Liu

All Dissertations

Diabetes mellitus, the third most common disease in the world, is a chronic metabolic disorder caused by a failure of insulin production and/or an inability to respond to insulin. Specifically, type 1 diabetes is a disorder characterized by targeted autoimmune-directed destruction of a patient's beta-cell population within the pancreatic islets of Langerhans. The current primary treatment for type 1 diabetes is daily multiple insulin injections. However, this treatment cannot provide sustained physiological release, and the insulin amount is not finely tuned to glycemia. Pancreatic transplants or islet transplants would be the preferred treatment method but the lack of ...


Development And Verification Of A Test System To Quantify Strain Of An Optical Displacement Indicator And The Design Of A Strain Indicating Prototype, Josh Lake Dec 2013

Development And Verification Of A Test System To Quantify Strain Of An Optical Displacement Indicator And The Design Of A Strain Indicating Prototype, Josh Lake

All Theses

The organic-rich Middle Devonian Marcellus Shale of the Appalachian basin is a rapidly developing natural gas play. Stratigraphic boundaries of the Marcellus Shale in Westmoreland County, Pennsylvania were identified using geophysical logs from 10 vertical gas-producing wells in a 23 sq. km area. Gamma-ray, bulk density, and resistivity well logs were examined to assess hydrocarbon potential. Values of porosity, total organic carbon (TOC), and water saturation (SW) were derived and mapped by incorporating well-log data into Marcellus-specific formulas. Gamma-ray, penetration (minutes per foot drilled), and mud-logging gas (total gas) from 12 horizontal wells from within the study area were also ...


Scratch Damage Evolution On Metals In Total Joint Replacements, Caleb Eljach Dec 2013

Scratch Damage Evolution On Metals In Total Joint Replacements, Caleb Eljach

All Theses

The goal of total joint replacement (TJR) is to replace nonfunctioning joint components and relieve pain, improve quality of life, and to improve joint function. Although TJR is a successful procedure, more than 54,000 knee revisions occur each year due to factors, such as wear, loosening, infection, fracture, instability, and patient related factors (Ranawat, 2010). TJRs consist of components typically composed of polyethylene and a metallic counterface (Navarro, 2008). The sliding contact that occurs between the metal and polyethylene components has been well studied and is shown to produce both surface damage and wear of the implant components (Barbour ...


Ion Channel-Mediated Hydrostatic Pressure Mechanotransduction In Urothelial Cells, Kevin Champaigne Aug 2013

Ion Channel-Mediated Hydrostatic Pressure Mechanotransduction In Urothelial Cells, Kevin Champaigne

All Dissertations

A majority of men and women aged 40 and over experience lower urinary tract symptoms, including urgency, incontinence, and frequency, which often affect the individual's quality of life. Although often considered a simple structure, the bladder is a complex system with sophisticated sensory and motor feedback mechanisms that allow for the sensation of fullness and pain, reflexive responses to bladder filling, and conscious control over the time and place of micturition. Although disruptions of these sensory mechanisms are believed to cause certain lower urinary tract dysfunctions, the specific mechanisms involved in sensing bladder fullness, distension, tension, or pressure at ...


Experimental Development And Analysis Of A Novel Setup For Insulated Dielectrophoresis, Johnie Hodge Aug 2013

Experimental Development And Analysis Of A Novel Setup For Insulated Dielectrophoresis, Johnie Hodge

All Theses

Dielectrophoresis has long been studied and utilized for the manipulation of microscale particles in solution. This phenomenon is due to the induced polarization of dielectric particles subjected to an electric field. When the field is also inhomogeneous in terms of the distribution of its strength through space, the polarized particles move and come to rest in certain areas due to the relationship between their and the solvent's relative permittivities. If the electric field is homogenous, such as within a parallel plate capacitor, the particles are polarized according to their permittivity and the field's frequency, but they will not ...


Spatial Control Of Magnetic Nanoparticles Integrated With Cellular Spheroids As Tissue Engineered Building Blocks, Brandon Mattix Aug 2013

Spatial Control Of Magnetic Nanoparticles Integrated With Cellular Spheroids As Tissue Engineered Building Blocks, Brandon Mattix

All Dissertations

Magnetic nanoparticles (MNPs) have been investigated in tissue engineering applications to provide in situ imaging, drug delivery, and tissue patterning, but direct and prolonged interaction between cells and MNPs can have adverse effects on cell function. Therefore, methods which reduce or limit the interaction of MNPs with cells, or utilize more biocompatible MNP-based strategies will improve upon the commonly used iron oxide MNPs. We investigated a variety of methods to improve upon the use of MNPS in tissue engineering.
Cell aggregates, or spheroids, have been used as tissue engineered building blocks that can closely mimic the native three-dimensional in vivo ...


A Novel Hybrid Hydrogel For Scaffold-Mediated Gene Delivery, Jeremy Zhang Aug 2013

A Novel Hybrid Hydrogel For Scaffold-Mediated Gene Delivery, Jeremy Zhang

All Dissertations

Scaffold-mediated nonviral gene delivery avoids several drawbacks of systemic injection such as clearance by the reticulo-endothelial system and serum aggregation. Existing synthetic and natural polymers used in gene delivery scaffolds are primarily derived from other tissue engineering applications with design parameters focused on the physicochemical properties of the scaffold and its biocompatibility. Common synthetic materials used in polymeric scaffolds such as PEG are practically bio-inert with minimal cell and protein interaction. Therefore, an opportunity exists for the rational design novel gene delivery scaffolds with components capable of increasing the expression of incorporated transgene by including scaffold components that interact with ...


Implantable Biosensors For Physiologic Status Monitoring During Hemorrhage, Christian Kotanen Aug 2013

Implantable Biosensors For Physiologic Status Monitoring During Hemorrhage, Christian Kotanen

All Dissertations

Trauma diagnostics and management are major aims of research for implantable amperometric enzyme biosensor technology. Biosensors are capable of monitoring metabolic variables in a minimally invasive manner and have great potential to augment current wireless vital sign monitoring technologies in order to make a more robust physiologic status monitoring platform. The dual responsive Electrochemical Cell-on-a-Chip Microdisc Electrode Array (ECC MDEA 5037) is a recently developed electrochemical transducer for use in a wireless, implantable biosensor system for the continuous measurement of interstitial glucose and lactate. Hyperglycemia arising from insulin resistance and hyperlactatemia arising from anaerobic metabolism both occur following trauma and ...


Feeling For Failure: Haptic Force Perception Of Soft Tissue Constraints In A Simulated Minimally Invasive Surgery Task, Lindsay Long Aug 2013

Feeling For Failure: Haptic Force Perception Of Soft Tissue Constraints In A Simulated Minimally Invasive Surgery Task, Lindsay Long

All Dissertations

In minimally invasive surgery (MIS), the ability to accurately interpret haptic information and apply appropriate force magnitudes onto soft tissue is critical for minimizing bodily trauma. Force perception in MIS is a dynamic process in which the surgeon's administration of force onto tissue results in useful perceptual information which guides further haptic interaction and it is hypothesized that the compliant nature of soft tissue during force application provides biomechanical information denoting tissue failure. Specifically, the perceptual relationship between applied force and material deformation rate specifies the distance remaining until structural capacity will fail, or indicates Distance-to-Break (DTB). Two experiments ...


Problems In The Study And Use Of Ac Dielectrophoresis And Their Consequences: A Study Based On Comsol Multiphysics Modeling, Vandana Devi Pandian Babu Aug 2013

Problems In The Study And Use Of Ac Dielectrophoresis And Their Consequences: A Study Based On Comsol Multiphysics Modeling, Vandana Devi Pandian Babu

All Theses

Dielectrophoresis (or DEP) is an important phenomenon which is induced when a dielectric particle is placed in a non-uniform electric field. The force generated by DEP has been exploited for various micro and nano fluidics applications like positioning, sorting and separation of particles involved in medical diagnostics, drug discovery, cell therapeutics, biosensors, microfluidics, nanoassembly, particle filtration etc. The integration of DEP systems into the microfluidics enables inexpensive, fast, highly sensitive, highly selective, label-free detection and also the analysis of target bioparticles.

This work aims to provide a complete compilation of the factors affecting the DEP force. It elucidates the underlying ...