Nicholas Ferrell

Microfabrication and nanomechanical characterization of polymer microelectromechanical system for biological applications

Polymer microelectromechanical system (MEMS) devices are promising for biological applications such as development of biosensors and biomechanical devices. In order to develop polymer biological MEMS (BioMEMS), polymer microfabrication techniques are required, and the nanomechanics studies, including measurement of the nanomechanical properties of the polymer materials, must be carried out. This article presents the development of soft lithography based polymer BioMEMS microfabrication techniques and systematic studies on the nanomechanical characterization of the polymer thin films and beams. Poly (methylmethacrylate) (PMMA) and poly (propyl methacrylate) (PPMA) are used to make the polymer beams for MEMS integration. The hardness, elastic modulus and creep behavior of PMMA and PPMA thin films and microstructures were measured using continuous stiffness measurement nanoindentation technique, and the scratch resistance of the polymer thin films was measured using a nanoscratch technique. The elastic modul...

Vacuum-assisted cell seeding in a microwell cell culture system.

We present a simple method to actively pattern individual cells and groups of cells in a polymer-based microdevice using vacuum-assisted cell seeding. Soft lithography is used to mold polymer microwells with various geometries on top of commercially available porous membranes. Cell suspensions are placed in a vacuum filtration setup to pull culture medium through the microdevice, trapping the cells in the microwells. The process is evaluated by determining the number of cells per microwell for a given cell seeding density and microwell geometry. This method is tested with adherent and nonadherent cells (NIH 3T3 fibroblasts, PANC-1 pancreatic ductal epithelial-like cells, and THP-1 monocytic leukemia cells). These devices could find applications in high-throughput cell screening, cell transport studies, guided formation of cell clusters, and tissue engineering.

Simultaneous fabrication of hybrid arrays of nanowires and micro/nanoparticles by dewetting on micropillars

Large and well-defined arrays of both nanowires and micro/nanoparticles or only micro/nanoparticles are fabricated from aqueous solutions through a one-step dewetting process on an array of polydimethylsiloxane (PDMS) micropillars.

Fabrication of Piezoelectric Polyvinylidene Fluoride (PVDF) Microstructures by Soft Lithography for Tissue Engineering and Cell Biology Applications

A method for the fabrication of piezoelectric polyvinylidene fluoride (PVDF) microstructures is described. Embossed and individual features with highly defined geometries at the microscale were obtained using soft lithography-based techniques. Various structure geometries were obtained, including pillars (three different aspect ratios), parallel lines, and criss-crossed lines. SEM characterization revealed uniform patterns with dimensions ranging from 2 µm n 15 µm. Human osteosarcoma (HOS) cell cultures were used to evaluate the cytocompatibility of the microstructures. SEM and fluorescence microscopy showed adequate cell adhesion, proliferation, and strong interaction with tips and corners of the microdiscontinuities. Microfabricated piezoelectric PVDF structures could find applications in the fabrication of mechanically active tissue engineering scaffolds, and the development of dynamic sensors at the cellular and subcellular levels.

Adhesion properties of polymer/silicon interfaces for biological micro-/nanoelectromechanical systems applications

Polymers are used in biological micro-nanoelectromechanical systems (BioMEMS/NEMS) applications due to their desirable mechanical properties, biocompatibility, and reduced cost relative to silicon microfabrication processes. Understanding the interfacial properties of the films that are used in BioMEMS/NEMS serves as a useful tool in obtaining higher device yield and greater mechanical reliability. In this study, polystyrene (PS) and glycidyl-ether-bisphenol-A novolac polymer (SU8) on silicon substrates were investigated. SU8 is a commonly used material in MEMS/NEMS fabrication, while PS is evaluated for its potential use in BioMEMS/NEMS for interaction with biological cells. The aim is to examine the delamination of the interfaces. Nanoindentation was employed on the PS/Si and SU8/Si film systems coated with a thin metallic layer of Cr to facilitate delamination. The interfacial adhesion energy was determined from measuring the size of the resulting delamination and the contact radius. Scale effects were...

Polymer MEMS for Measuring Single Cell Forces

We have developed a polymer MEMS sensor for measuring mechanical forces generated by single adherent cells. Mechanical forces are known to play a role in cell regulation, and measuring these forces is an important step in understanding cellular mechanotransduction. The sensor consists of four polystyrene microcantilever beams with cell adhesion pads at each end. Finite element analysis was used to guide the design of a compound cantilever to allow measurement of forces in multiple directions. The device was evaluated by measuring forces generated by WS-1 human skin fibroblasts. A single cell was placed on the sensor using a custom micromanipulator. Forces were calculated by optically measuring the deflection of each probe during cell attachment and spreading. Measurements were performed on normal cells and those treated with cytochalasin D to disrupt the actin cytoskeleton. Cytochalasin D treated cells showed a significant decrease in force. This device can be used to evaluate the mechanical response of cells to a variety of chemical, mechanical, and other environmental stimuli.Copyright

Controlled silica deposition on soft-lithography fabricated poly-L-lysine templates

We describe the combination of soft-lithographic patterning and biomolecule-induced deposition to create microscale patterns of silica on a diverse array of substrates. A soft lithographic technique was used to create a sacrificial layer of the polymer poly(n-propyl methacrylate) (PPMA) on the desired substrate. Subsequently, poly-L-lysine was deposited on the substrate, after which removal of the PPMA yielded a pattern of PLL on the substrate. Exposure of the PLL template to a silicic acid solution resulted in silica deposition in the pattern spatially and geometrically controlled by the PLL. With this procedure, we have created both continuous and discontinuous silica patterns on metallic, ceramic, and polymer substrates. While morphology of the deposited silica varied between substrates, the ability to pattern silica through this templated growth was demonstrated on all investigated substrates. EDS, optical micrography, and SEM analysis verified the controlled deposition of silica on the PLL template patterns. This PLL template-mediated induction of silica formation may facilitate the incorporation of silica in new microdevices and serve as a prototype process for controlled deposition with other biomolecule-material systems.

Use of Soft Lithography for Multi-layer MicroMolding (MMM) of 3-D PCL Scaffolds for Tissue Engineering

Tissue engineering scaffolds with precisely controlled geometries, particularly with surface features smaller than typical cell dimensions (1-10μm), can improve cellular adhesion and functionality. In this paper, soft lithography was used to fabricate polydimethylsiloxane (PDMS) stamps of arrays of parallel 5μm wide, 5μm deep grooves separated by 45 μm ridges, and an orthogonal grid of lines with the same geometry. Several methods were compared for the fabrication of 3-D multi-layer polycaprolactone (PCL) scaffolds with precise features. First, micromolding in capillaries (MIMIC) was used to deliver the polymer into the small grooves by capillarity; however the resultant lines were discontinuous and not able to form complete lines. Second, spin coating and oxygen plasma were combined to build 3-D scaffolds with the line pattern. The resultant scaffolds had good alignment and adhesion between layers; however, the upper layer collapsed due to the poor mechanical rigidity. Finally, a new multi-layer micromolding (MMM) method was developed and successfully applied with the grid pattern to fabricate 3-D scaffolds. Scanning electron microscopy (SEM) characterization showed that the multi-layered scaffolds had high porosity and precisely controlled 3-D structures.