Dennis Edmondson

Influence of cell adhesion and spreading on impedance characteristics of cell-based sensors.

Impedance measurements of cell-based sensors are a primary characterization route for detection and analysis of cellular responses to chemical and biological agents in real time. The detection sensitivity and limitation depend on sensor impedance characteristics and thus on cell patterning techniques. This study introduces a cell patterning approach to bind cells on microarrays of gold electrodes and demonstrates that single-cell patterning can substantially improve impedance characteristics of cell-based sensors. Mouse fibroblast cells (NIH3T3) are immobilized on electrodes through a lysine-arginine-glycine-aspartic acid (KRGD) peptide-mediated natural cell adhesion process. Electrodes are made of three sizes and immobilized with either covalently bound or physically adsorbed KRGD (c-electrodes or p-electrodes). Cells attached to c-electrodes increase the measurable electrical signal strength by 48.4%, 24.2%, and 19.0% for three electrode sizes, respectively, as compared to cells attached to p-electrodes, demonstrating that both the electrode size and surface chemistry play a key role in cell adhesion and spreading and thus the impedance characteristics of cell-based sensors. Single cells patterned on c-electrodes with dimensions comparable to cell size exhibit well-spread cell morphology and substantially outperform cells patterned on electrodes of other configurations.

Centrifugal electrospinning of highly aligned polymer nanofibers over a large area

Well-ordered one-dimensional nanostructures are enabling important new applications in textiles, energy, environment and bioengineering owing to their unique and anisotropic properties. However, the production of highly aligned nanofibers in a large area remains a significant challenge. Here we report a powerful, yet economical approach that integrates the concepts of the parallel-electrode electrospinning with centrifugal dispersion to produce nanofibers with a high degree of alignment and uniformity at a large scale. We first demonstrated this approach with polyvinylidene fluoride to show how experimental parameters regulate fiber properties, and then with chitosan, a natural polymer, and polyethylene oxide, a synthetic polymer, to illustrate the versatility of the system. As a model application, we then demonstrated the significance of fiber alignment in improving the piezoelectric effect for voltage generation. The technique presented here may be used for mass production of aligned nanofibers of various polymers for a myriad of applications.

High-throughput and high-yield fabrication of uniaxially-aligned chitosan-based nanofibers by centrifugal electrospinning.

The inability to produce large quantities of nanofibers has been a primary obstacle in advancement and commercialization of electrospinning technologies, especially when aligned nanofibers are desired. Here, we present a high-throughput centrifugal electrospinning (HTP-CES) system capable of producing a large number of highly-aligned nanofiber samples with high-yield and tunable diameters. The versatility of the design was revealed when bead-less nanofibers were produced from copolymer chitosan/polycaprolactone (C-PCL) solutions despite variations in polymer blend composition or spinneret needle gauge. Compared to conventional electrospinning techniques, fibers spun with the HTP-CES not only exhibited superior alignment, but also better diameter uniformity. Nanofiber alignment was quantified using Fast Fourier Transform (FFT) analysis. In addition, a concave correlation between the needle diameter and resultant fiber diameter was identified. This system can be easily scaled up for industrial production of highly-aligned nanofibers with tunable diameters that can potentially meet the requirements for various engineering and biomedical applications.

Aligned Chitosan‐Polycaprolactone Polyblend Nanofibers Promote the Migration of Glioblastoma Cells

In vitro models that accurately mimic the microenvironment of invading glioblastoma multiform (GBM) cells will provide a high-throughput system for testing potential anti-invasion therapies. Here, the ability of chitosan-polycaprolactone polyblend nanofibers to promote a migratory phenotype in human GBM cells by altering the nanotopography of the nanofiber membranes is investigated. Fibers are prepared with diameters of 200 nm, 400 nm, and 1.1 μm, and are either randomly oriented or aligned to produce six distinct nanotopographies. Human U-87 MG GBM cells, a model cell line commonly used for invasion assays, are cultured on the various nanofibrous substrates. Cells show elongation and alignment along the orientation of aligned fibers as early as 24 h and up to 120 h of culture. After 24 h of culture, human GBM cells cultured on aligned 200 nm and 400 nm fibers show marked upregulation of invasion-related genes including β-catenin, Snail, STAT3, TGF-β, and Twist, suggesting a mesenchymal change in these migrating cells. Additionally, cells cultured on 400 nm aligned fibers show similar migration profiles as those reported in vivo, and thus these nanofibers should provide a unique high-throughput in vitro culture substrate for developing anti-migration therapies for the treatment of GBM.

Design and evaluation of a nanoscale differential tensile test device for nanofibers

The development of nanofibers could open new avenues in fundamental research and novel applications. Tensile properties of these nanofibers are a good indicator of their overall mechanical response. However, accurate measurements of tensile properties at the micro- and nanoscales remain a challenge. Here we report a simple but highly efficient differential nanoscale tensile test device constructed from off the shelf state-of-the-art components. The unique feature of this device is that it can measure the applied load and specimen’s deformation in the nanonewton and nanometer scales, respectively. First experimental results on electrospun nanofibers are reported.

Uniaxially-aligned PVDF nanofibers as a sensor and transmitter for biotelemetry

Biotelemetry has become an important part of medical research for patient care by remotely monitoring continuing biological processes and physiological functions. However, current biotelemetry systems are complex requiring multiple electronic components to function: a battery, a sensor, and a transmitter, and a receiver. Another paramount concern of biotelemetry is the coupling of its in vivo portion to external supporting equipment. Here we report a novel biotelemetry device made primarily of a coiled bundle of uniaxially-aligned biocompatible polyvinylidene fluoride (PVDF) nanofibers of ∼200 nm in diameter and with piezoelectric properties that can serve concurrently as a power source, sensor, and transmitter. We tested this device on a cantilever beam that was periodically deflected at its free end. Without a power supply the coil of a nanofiber bundle is shown to generate and transmit an electrical signal wirelessly in response to the beam deflection which was received by an external receiver. The coil of a nanofiber bundle was encapsulated in a thin biocompatible polymer shell for device integrity and moisture isolation. Our results suggest that the device can potentially serve as a mechanical sensor and biotelemeter for various in vitro and in vivo biomedical applications.