Derek J. Hansford

Nanopore Technology for Biomedical Applications

The ability to create well-defined and controlled interfaces has been an area of great interest over the last few years, particularly in the biomedical arena. This paper will describe the development of technology for the fabrication of nanopore membranes, and their operation in biological environments. With monodisperse pores sizes as small as 10 nanometers, these membranes offer advantages in their reproducibility, and their ability to be integrated with controlled biochemical surface modification protocols. A comprehensive review of results in the areas of nanopore and biocapsule microfabrication technologies, biocompatibility of nanomembrane materials, biologically appropriate post-processing protocols (bonding, sterilization), surface modification protocols, and appropriate mass transport models will be presented. The results point to the potential of using such technologies for therapeutic applications including immunoisolation biocapsules, drug delivery devices, and targeted biorecognition platforms.

Nanoporous anti-fouling silicon membranes for biosensor applications

The ability to create biocompatible well-controlled membranes has been an area of great interest over the last few years, particularly for biosensor applications. The present study describes the fabrication and characterization of novel nanoporous micromachined membranes that exhibit selective permeability and low biofouling. Results indicate that such membranes can be fabricated with uniform pore sizes capable of the simultaneous exclusion of albumin and diffusion of glucose. Compared to polymeric membranes of similar pore size, micromachined silicon membranes allowed more than twice the amount of glucose diffusion after 240 min and complete albumin exclusion. Moreover, membranes exhibit no morphological change or degradability in the presence of biological proteins and fluids at 37 degrees C. The results point to the potential of using such membranes for implantable biosensor applications. With monodisperse pores sizes as small as 10 nm, these membranes offer advantages in their reproducibility, stability, and ability to be integrated in silicon-based biosensing technology.

Polymer–Ceramic Composites for Microwave Applications: Fabrication and Performance Assessment

We present a novel technique to fabricate conformal and pliable substrates for microwave applications including systems-on-package. The produced materials are fabricated by combining ceramic powders with polymers to generate a high-contrast substrate that is concurrently pliable (bendable). Several such polymer-ceramic substrates are fabricated and used to examine the performance of a patch antenna and a coupled line filter. This paper presents the substrate mixing method while measurements are given to evaluate the loss performance of the substrates. Overall, the fabricated composites lead to flexible substrates with a permittivity of up to epsivr=20 and sufficiently low loss

Micromachined interfaces: new approaches in cell immunoisolation and biomolecular separation

As a novel therapeutic application of microfabrication technology, a micromachined membrane-based biocapsule is described for the transplantation of protein-secreting cells without the need for immunosuppression. This new approach to cell encapsulation is based on microfabrication technology whereby immunoisolation membranes are bulk and surface micromachined to present uniform and well-controlled pore sizes as small as 10 nm, tailored surface chemistries, and precise microarchitecture. Through its ability to achieve highly controlled microarchitectures on size scales relevant to living systems (from microm to nm), microfabrication technology offers unique opportunities to more precisely engineer biocapsules that allow free exchange of the nutrients, waste products, and secreted therapeutic proteins between the host (patient) and implanted cells, but exclude lymphocytes and antibodies that may attack foreign cells. Microfabricated inorganic encapsulation devices may provide biocompatibility, in vivo chemical and mechanical stability, tailored pore geometries, and superior immunoisolation for encapsulated cells over conventional encapsulation approaches. By using microfabrication techniques, structures can be fabricated with spatial features from the sub-micron range up to several millimeters. These multi-scale structures correspond well with hierarchical biological structures, from proteins and sub-cellular organelles to the tissue and organ levels.

Surface modification of silicon and polydimethylsiloxane surfaces with vapor-phase-deposited ultrathin fluorosilane films for biomedical nanodevices

Ultrathin coatings of fluorosilane films for silicon and polydimethylsiloxane (PDMS) nanochannels are desirable to control the hydrophobicity of the surface and reduce or prevent undesired protein adsorption or cell interactions critical for the performance of most biomedical micro/nanodevices. Surface modifications using vapor-phase deposition become increasingly important for some biomedical nanodevices and have advantages over liquid-phase deposition since the vapor phase can permeate more efficiently into silicon nanochannels. In this study, vapor-phase deposition was used to deposit ultrathin films of four fluorosilanes on silicon and PDMS and identify deposition conditions for an optimal process. The films were characterized by means of a contact angle analyzer for hydrophobicity, an ellipsometer for film thickness, and an atomic force microscope for surface roughness of these films. Results of this study and relevant mechanisms are the subject of this article.

Isotropic micropatterned silica coatings on zirconia induce guided cell growth for dental implants

UNLABELLED Titanium implants are the gold standard in dentistry; however, problems such as gingival tarnishing and peri-implantitis have been reported. For zirconia to become a competitive alternative dental implant material, surface modification techniques that induce guided tissue growth must be developed. OBJECTIVES To develop alternative surface modification techniques to promote guided tissue regeneration on zirconia materials, for applications in dental implantology. METHODS A methodology that combined soft lithography and sol-gel chemistry was used to obtain isotropic micropatterned silica coatings on yttria-stabilized zirconia substrates. The materials were characterized via chemical, structural, surface morphology approaches. In vitro biological behavior was evaluated in terms of early adhesion and viability/metabolic activity of human osteoblast-like cells. Statistical analysis was conducted using one-way ANOVA/Tukey HSD post hoc test. RESULTS Isotropic micropatterned silica coatings on yttria-stabilized zirconia substrates were obtained using a combined approach based on sol-gel technology and soft lithography. Micropatterned silica surfaces exhibited a biocompatible behavior, and modulated cell responses (i.e. inducing early alignment of osteoblast-like cells). After 7d of culture, the cells fully covered the top surfaces of pillar microstructured silica films. SIGNIFICANCE The micropatterned silica films on zirconia showed a biocompatible response, and were capable of inducing guided osteoblastic cell adhesion, spreading and propagation. The results herein presented suggest that surface-modified ceramic implants via soft lithography and sol-gel chemistry could potentially be used to guide periodontal tissue regeneration, thus promoting tight tissue apposition, and avoiding gingival retraction and peri-implantitis.

Nanotribological characterization of fluoropolymer thin films for biomedical micro/nanoelectromechanical system applications

A vapor phase deposition system was designed to coat uniform, conformal and ultrathin coatings of fluoropolymer and fluorosilane thin films inside silicon nanochannels. Surface modifications using vapor phase deposition become increasingly important for biomedical micro/nanoelectromechanical system (BioMEMS/NEMS) applications and have advantages over liquid phase deposition since the vapor can permeate more efficiently into silicon nanochannels. In this article, we explore the use of vapor phase deposition to deposit ultrathin films of two fluoropolymers and a fluorosilane, identifying deposition parameters to optimize the process. The films are desirable to control the hydrophobicity of the surface and reduce or prevent undesired protein adsorption or cell interactions, which may cause detrimental effects to the performance of most BioMEMS/NEMS devices. The films were characterized by means of a contact angle analyzer for hydrophobicity and an ellipsometer for film thickness. Atomic force microscopy was ...

Microfabricated mimics of in vivo structural cues for the study of guided tumor cell migration

Guided cell migration plays a crucial role in tumor metastasis, which is considered to be the major cause of death in cancer patients. Such behavior is regulated in part by micro/nanoscale topographical cues present in the parenchyma or stroma in the form of fiber-like and/or conduit-like structures (e.g., white matter tracts, blood/lymphatic vessels, subpial and subperitoneal spaces). In this paper we used soft lithography micromolding to develop a tissue culture polystyrene platform with a microscale surface pattern that was able to induce guided cell motility along/through fiber-/conduit-like structures. The migratory behaviors of primary (glioma) and metastatic (lung and colon) tumors excised from the brain were monitored via time-lapse microscopy at the single cell level. All the tumor cells exhibited axially persistent cell migration, with percentages of unidirectionally motile cells of 84.0 ± 3.5%, 58.3 ± 6.8% and 69.4 ± 5.4% for the glioma, lung, and colon tumor cells, respectively. Lung tumor cells showed the highest migratory velocities (41.8 ± 4.6 μm h(-1)) compared to glioma (24.0 ± 1.8 μm h(-1)) and colon (26.7 ± 2.8 μm h(-1)) tumor cells. This platform could potentially be used in conjunction with other biological assays to probe the mechanisms underlying the metastatic phenotype under guided cell migration conditions, and possibly by itself as an indicator of the effectiveness of treatments that target specific tumor cell motility behaviors.

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.