BioMEMS PROJECTS

Minimally invasive procedures for the treatment of coronary artery disease have used catheter-based intravascular ultrasound (IVUS) imaging for general navigation and differentiation of diseased and healthy tissue as well as deployment and placement evaluation of intracoronary stents. Unfortunately, the unfocused nature of conventional lead zirconium titanate (PZT) transducers results in inferior image quality.

Consequently, we are exploiting MEMS technology to fabricate spherically focused microtransducers using polyvinylidene difluoride (PVDF) film and a membrane deflection technique that is compatible with CMOS circuit fabrication (Figure 1). Prototype micromachined Ultrasonic transducers with 0.5-2.0 mm-diameter apertures and f-numbers ranging from 1.3-4.0 have been fabricated and characterized (Figure 2).

Successful bone regeneration requires an osteoconductive surface or matrix to promote the growth of osteoblastic progenitor cells throughout the tissue volume where bone is desired. In normal fracture healing, the osteoconductive environment is usually provided by the local fracture hematoma and resulting fibrin clot. However, when healing is deficient or delayed, transplantation of osteogenic cells on an osteoconductive scaffold can provide an effective bone graft. Bone marrow aspirates contain a small fraction (~50 ppm) of osteoblastic progenitor cells (also known as Connective Tissue Progenitors - CTPs) that can differentiate into osteoblasts. Recent investigations have confirmed that bone healing can be significantly enhanced with an increase in the local CTP concentration at a fracture site. This increase in concentration was achieved by using a matrix surface as a site for selective attachment for CTPs. Other investigations have demonstrated that growth characteristics of differentiated cells can be influenced by the surrounding surface topography. Therefore, we are investigating role of surface topography on CTP growth characteristics as a potential avenue to improving the efficacy of bone grafting procedures.

Soft-lithography was used to micro-textured PDMS substrates comprising posts that were 6 µm high and 5-40 µm in diameter; and channels that were 45 µm wide separated by 5 µm wide ridges (Figure 1).

Numerous research and commercialization efforts on implantable biomedical microsystems have often focused on the development of device designs and associated fabrication protocols with the intent of achieving specific, often mechanical and short-term, functionality. Although this development approach might be suitable for certain biomedical research applications, requirements for clinical performance necessitate an examination of biocompatibility. The body's natural defense mechanism that begins with inflammation coupled with the corrosive effects of biofluids can disrupt the functionality, or even, destroy microsystems. Conventional strategies for the deployment of implantable microsystems based on silicon and related microelectronics materials have generally relied on encapsulating protective and bulky packaging to isolate the microsystem from the hostile body environment. For example, micromachined pressure sensors are encapsulated with biocompatible silicone gels to isolate the piezoresistive sensor from body fluids. The protective packaging approaches can result in two primary drawbacks: attenuation of signal/stimulus that must be communicated between the physiological environment and microsystem; and, increased size that detracts from the benefits of miniaturization particularly when working in constrained spaces or at the cellular level. Consequently, alternate approaches to enhance the biocompatibility of microsystems are desired. However, there is a paucity of data on the biocompatibility of microsystems materials, and most previous efforts usually relied on non-standard testing protocols. Therefore, we are assessing the biocompatibility of common microsystems materials using test protocols based on ISO 10993 standards.

Cytotoxicity of silicon, silicon dioxide (SiO2 ), and silicon nitride (Si3N4 ) was evaluated in vitro on the human lung (WI-38) cell line. Extracts were added to 80-90% confluent cell monolayers, which were then incubated for 48 hours. Light microscopy was used to examine the cell monolayers and scored a relative scale of 0-4 based on the degree of cellular destruction (Figure 1). All microsystems materials scored 0 while the negative and positive controls scored 0 and 4, respectively (Table I).

Table I: Cytotoxicity Score Summary

Material	Reactivity	Score
Negative Control - Polypropylene	None	0
Positive Control - Natural Black Rubber	Severe	4
Si	None	0
SiO2	None	0
Si3N4	None	0

Conventional skin resurfacing techniques using commercially available dermabraders or chemical peels may cause excessive bleeding or asymmetrical excisions, and are often time-consuming procedures that necessitate multiple sessions. Consequently, we have explored the feasibility of MEMS fabrication technology to develop miniature dermabrasion tools. Microfabrication and micromachining techniques offer the capability to precisely shape the abrading surfaces, and thereby, optimize skin resurfacing, minimize unnecessary tissue destruction, and amplify healing and restructuring of the epidermal surface.

The abrading microstructures were formed on silicon wafers by a bulk micromachining process based on isotropic xenon difluoride (XeF2) etching (Figure 1). The micromachined abraders (microdermabraders) were subsequently attached to a rotary bit, which was mounted onto a materials testing system and applied to human cadaveric skin (Figure 2). Afterwards, both dermabraded and neighboring intact regions were imaged and analyzed to assess abrasion quality

Figure 1: SEM image of ~50 µm-high silicon microdermabraders.

Figure 2: Photograph of experimental setup used to evaluate abrasion performance.

The silicon microdermabraders exhibited a clean, uniform abrading pattern on the cadaveric skin (Figure 3). Furthermore, the cut through the epidermal layer was consistently uniform leaving little debris and minimal pitting.

(a)                                                        (b) Figure 3: Optical micrographs of cadaveric skin before (a) and after (b) dermabrasion. The wrinkles and surface irregularities are eliminated by the silicon microdermabraders.

Although the compressive force required to drive the abrasion tool into the skin varied, the ~50 µm-height of the microdermabrader limited abrasion depth. Histological examination of the microdermabraded skin and its neighboring intact region confirmed the selective removal of the ~40 µm-thick stratum corneum layer of the epidermis (Figure 4).

Figure 4: Histological image of a skin sample showing both intact and dermabraded regions. The height of the microdermabraders (~50 µm) limits the abrasion depth, and consequently, the stratum corneum was been completely removed without any observable damage to the underlying epidermal tissue.