Masaru P. Rao

Inductively Coupled Plasma Etching of Bulk Titanium for MEMS Applications

Traditionally, microelectromechanical systems MEMS have relied heavily on materials used in integrated circuit fabrication, such as single-crystal silicon. However, due to the mechanical nature of some MEMS devices, performance may be limited by the intrinsic properties of these materials. Therefore, additional material systems such as metals are being considered as potential candidates for bulk MEMS because their relative ductility may reduce the risk of failure associated with brittle silicon. 1 Recent developments have allowed for the realization of bulk titanium MEMS for devices that require higher fracture toughness and/or resistance to harsh environments. 2

Bulk Micromachined Titanium Microneedles

Microneedle-based drug delivery has shown considerable promise for enabling painless transdermal and hypodermal delivery of conventional and novel therapies. However, this promise has yet to be fully realized due in large part to the limitations imposed by the micromechanical properties of the material systems being used. In this paper, we demonstrate titanium-based microneedle devices developed to address these limitations. Microneedle arrays with in-plane orientation are fabricated using recently developed high-aspect-ratio titanium bulk micromachining and multilayer lamination techniques. These devices include embedded microfluidic networks for the active delivery and/or extraction of fluids. Data from quantitative and qualitative characterization of the fluidic and mechanical performance of the devices are presented and shown to be in good agreement with finite-element simulations. The results demonstrate the potential of titanium micromachining for the fabrication of robust, reliable, and low-cost microneedle devices for drug delivery

Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype

Controlling the interactions between macrophages and biomaterials is critical for modulating the response to implants. While it has long been thought that biomaterial surface chemistry regulates the immune response, recent studies have suggested that material geometry may in fact dominate. Our previous work demonstrated that elongation of macrophages regulates their polarization toward a pro-healing phenotype. In this work, we elucidate how surface topology might be leveraged to alter macrophage cell morphology and polarization state. Using a deep etch technique, we fabricated titanium surfaces containing micro- and nanopatterned grooves, which have been previously shown to promote cell elongation. Morphology, phenotypic markers, and cytokine secretion of murine bone marrow derived macrophages on different groove widths were analyzed. The results suggest that micro- and nanopatterned grooves influenced macrophage elongation, which peaked on substrates with 400-500 nm wide grooves. Surface grooves did not affect inflammatory activation but drove macrophages toward an anti-inflammatory, pro-healing phenotype. While secretion of TNF-alpha remained low in macrophages across all conditions, macrophages secreted significantly higher levels of anti-inflammatory cytokine, IL-10, on intermediate groove widths compared to cells on other Ti surfaces. Our findings highlight the potential of using surface topography to regulate macrophage function, and thus control the wound healing and tissue repair response to biomaterials.

Single-mask, three-dimensional microfabrication of high-aspect-ratio structures in bulk silicon using reactive ion etching lag and sacrificial oxidation

This letter describes a simple method for three-dimensional microfabrication of complex, high-aspect-ratio structures with arbitrary surface height profiles in bulk silicon. The method relies on the exploitation of reactive ion etching lag to simultaneously define all features using a single lithographic masking step. Modulation of the mask pattern openings used to define the features results in etch depth variation across the pattern, which is then translated into surface height variation through removal of the superstructure above the etched floors. Utilization of a nonisotropic superstructure removal method based on sacrificial oxidation enables definition of high-aspect-ratio structures with vertical sidewalls and fine features. The utility of the approach is demonstrated in the fabrication of a sloping electrode structure for application in a hybrid micromirror device.

Robust penetrating microelectrodes for neural interfaces realized by titanium micromachining

Neural prosthetic interfaces based upon penetrating microelectrode devices have broadened our understanding of the brain and have shown promise for restoring neurological functions lost to disease, stroke, or injury. However, the eventual viability of such devices for use in the treatment of neurological dysfunction may be ultimately constrained by the intrinsic brittleness of silicon, the material most commonly used for manufacture of penetrating microelectrodes. This brittleness creates predisposition for catastrophic fracture, which may adversely affect the reliability and safety of such devices, due to potential for fragmentation within the brain. Herein, we report the development of titanium-based penetrating microelectrodes that seek to address this potential future limitation. Titanium provides advantage relative to silicon due to its superior fracture toughness, which affords potential for creation of robust devices that are resistant to catastrophic failure. Realization of these devices is enabled by recently developed techniques which provide opportunity for fabrication of high-aspect-ratio micromechanical structures in bulk titanium substrates. Details are presented regarding the design, fabrication, mechanical testing, in vitro functional characterization, and preliminary in vivo testing of devices intended for acute recording in rat auditory cortex and thalamus, both independently and simultaneously.

Size-dependent piezoelectric and mechanical properties of electrospun P(VDF-TrFE) nanofibers for enhanced energy harvesting

Piezoelectricity-based energy harvesting from wasted mechanical energies has garnered an increasing attention as a clean energy source. Especially, flexible organic piezoelectric materials provide an opportunity to exploit their uses in mechanically challenging areas where brittle inorganic counterparts have mechanical limitations. In this regard, electrospinning has shown its advantages of producing poly(vinylidene fluoride) (PVDF)-based nanofibrous structures without the necessity of a secondary processing to induce/increase piezoelectric properties. However, the effects of electrospun fiber dimension, one of the main morphological parameters in electrospun fibers, on piezoelectricity have not been fully understood. In this study, two dependent design of experiments (DOEs) were utilized to systematically control the dimensions of electrospun poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) to produce nanofibers having their diameter ranging from 1000 to sub-100 nm. Such a dimensional reduction resulted in the increase of piezoelectric responsible electroactive phase content and the degree of crystallinity. These changes in crystal structure led to approximately 2-fold increase in piezoelectric constant as compared to typical P(VDF-TrFE) thin films. More substantially, the dimensional reduction also increased the Youngs modulus of the nanofibers up to approximately 80-fold. The increases in piezoelectric constant and Youngs modulus collectively enhanced piezoelectric performance, resulting in the exponential increase in electric output of nanofiber mats when the fiber diameters were reduced from 860 nm down to 90 nm. Taken together, the results suggest a new strategy to improve the piezoelectric performance of electrospun P(VDF-TrFE) via optimization of their electromechanical and mechanical properties.

Comparative endothelial cell response on topographically patterned titanium and silicon substrates with micrometer to sub-micrometer feature sizes.

In this work, we evaluate the in vitro response of endothelial cells (EC) to variation in precisely-defined, micrometer to sub-micrometer scale topography on two different substrate materials, titanium (Ti) and silicon (Si). Both substrates possess identically-patterned surfaces composed of microfabricated, groove-based gratings with groove widths ranging from 0.5 to 50 µm, grating pitch twice the groove width, and groove depth of 1.3 µm. These specific materials are chosen due to their relevance for implantable microdevice applications, while grating-based patterns are chosen for the potential they afford for inducing elongated and aligned cellular morphologies reminiscent of the native endothelium. Using EA926 cells, a human EC variant, we show significant improvement in cellular adhesion, proliferation, morphology, and function with decreasing feature size on patterned Ti substrates. Moreover, we show similar trending on patterned Si substrates, albeit to a lesser extent than on comparably patterned Ti substrates. Collectively, these results suggest promise for sub-micrometer topographic patterning in general, and sub-micrometer patterning of Ti specifically, as a means for enhancing endothelialization and neovascularisation for novel implantable microdevice applications.

Titanium-based dielectrophoresis devices for microfluidic applications.

To date, materials selection in microfluidics has been restricted to conventional micromechanical materials systems such as silicon, glass, and various polymers. Metallic materials offer a number of potential advantages for microfluidic applications, including high fracture toughness, thermal stability, and solvent resistance. However, their exploitation in such applications has been limited. In this work, we present the application of recently developed titanium micromachining and multilayer lamination techniques for the fabrication of dielectrophoresis devices for microfluidic particle manipulation. Two device designs are presented, one with interdigitated planar electrodes defined on the floor of the flow channel, and the other with electrodes embedded within the channel wall. Using these devices, two-frequency particle separation and Z-dimensional flow visualization of the dielectrophoresis phenomena are demonstrated.

Simultaneous recording of rat auditory cortex and thalamus via a titanium-based, microfabricated, microelectrode device

Direct recording from sequential processing stations within the brain has provided opportunity for enhancing understanding of important neural circuits, such as the corticothalamic loops underlying auditory, visual, and somatosensory processing. However, the common reliance upon microwire-based electrodes to perform such recordings often necessitates complex surgeries and increases trauma to neural tissues. This paper reports the development of titanium-based, microfabricated, microelectrode devices designed to address these limitations by allowing acute recording from the thalamic nuclei and associated cortical sites simultaneously in a minimally invasive manner. In particular, devices were designed to simultaneously probe rat auditory cortex and auditory thalamus, with the intent of recording auditory response latencies and isolated action potentials within the separate anatomical sites. Details regarding the design, fabrication, and characterization of these devices are presented, as are preliminary results from acute in vivo recording.

Titanium-based multi-channel, micro-electrode array for recording neural signals

Micro-scale brain-machine interface (BMI) devices have provided an opportunity for direct probing of neural function and have also shown significant promise for restoring neurological functions lost to stroke, injury, or disease. However, the eventual clinical translation of such devices may be hampered by limitations associated with the materials commonly used for their fabrication, e.g. brittleness of silicon, insufficient rigidity of polymeric devices, and unproven chronic biocompatibility of both. Herein, we report, for the first time, the development of titanium-based “Michigan” type multi-channel, microelectrode arrays that seek to address these limitations. Titanium provides unique properties of immediate relevance to microelectrode arrays, such as high toughness, moderate modulus, and excellent biocompatibility, which may enhance structural reliability, safety, and chronic recording reliability. Realization of these devices is enabled by recently developed techniques which provide the opportunity for fabrication of high aspect ratio micromechanical structures in bulk titanium substrates. Details regarding the design, fabrication, and characterization of these devices for eventual use in rat auditory cortex and thalamus recordings are presented, as are preliminary results.