Application of MEMS in Drug Delivery 161
Figure 7.8. BioMEMS micro-array prototype. The inner-reservoir surface area is larger
than it appears from a top view (A). The activation of the entire multi-array reservoir system
leads to dissolution of the reservoir sealing membrane, release of the drug, and the onset of
a “new” inflammatory response initiated by the exposed surface of the inner reservoir (B).
For color reference, see page 270.
Consequently, in the design and development of BioMEMS particular atten-
tion must be given to the component materials which during the life of the device
will become surface contact materials, as they could adversely affect the extent of
the inflammatory and wound healing response, and, by association, modulate the
therapeutic outcome of the BioMEMS outside the intended window of operation.
The state of the BioMEMS field described in Section 2 of this work clearly identifies
the use of titanium as a surface contacting material in devices that have reached
or are very close to reaching commercialization. Historically, the inert nature
of this material has rendered it useful in muskulo-skeletal applications which
require good biocompatibility and enhanced load bearing support. Other mate-
rials, such as PMMA and PDMS are presently under investigation to determine
their potential for combining their proven biocompatibility with MEMS based
micromachining technologies.
Finally, there is no exact biocompatibility sliding scale related to the BioMEMS
component materials, but, some pre-development guidance could be provided
based on the knowledge acquired through previous and present investigations:
(a) Determine which material components would present surface contact expo-
sure to the local biological environment,
(b) Evaluate the biocompatibility of BioMEMS surface contacting materials in
reference to recognized biocompatible materials standards,
(c) Evaluate the in vivo inflammatory and wound healing response of the critical
surface contact materials in a simple animal model, such as the subcutaneous
tissue of rats.
7.4.2 Fabrication Methods
BioMEMS are fabricated by adapting techniques developed for the semiconductor
industry. The platform technologies span from basic surface etching to fabrication
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162 G. Voskerician
of integrated complex programmable and structural elements. Table 7.1 outlines
the advantages of MEMS based fabrication technologies. Silicon and glass have
been the two major materials used in the micromachining of MEMS, mostly due
to their traditional use in the semiconductor industry as well as their suitability
for a variety of transducing applications.
14
Yet, the biological interface requires
a level of biocompatibility which surpasses that of silicon and glass. Further,
the inherent advantages of the polymer platform with respect to their material
state (hard, glassy or soft, and rubbery), established sterilization methods, and
flexibility of processing led to associated inclusion of materials such as silicone
rubber, polycarbonate, polyimide, and isobornyl acrylate as part of the BioMEMS
candidate materials.
Consequently, fabrication methods have expanded from the “hard” MEMS
technologies (bulk, surface, and high aspect ratio micromachining) to “soft”
manufacturing methods such as soft lithography and other polymer processing
techniques.
14
The fabrication process could affect the biocompatibility of a medical
device. The use of corrosive organic solvents and other processing components
which could leave behind even a trace amount of highly toxic residue will affect the
biocompatibility of the overall BioMEMS, if these surfaces are exposed to the local
biological environment. The traditional etching process involves the use of either
of the three highly biologically toxic etchants, potassium hydroxide (KOH), ethy-
lene diamine pyrochatechol (EDP) or tetramethyl ammonium hydroxide (TMAH).
These etchants attack silicon along preferred crystallographic directions. Masking
materials such as silicon nitride and photoresists such as SU-8 have also been
used.
14
Voskerician et al reported on the in vivo performance of silicon and
silicon based materials in a rodent model. It was determined that silicon and
SU-8 induced an elevated inflammatory and wound healing response compared
to silicon nitride.
53
In contrast, “soft” micromachining of PDMS or PMMA, also
known as micromolding does not require the use of highly corrosive compounds
in the fabrication process. These polymers are biocompatible, cost effective, and
lead to BioMEMS components with excellent sealing properties (PDMS) and elastic
properties, which are absent in the case of silicon based MEMS.
14
Thus, the choice of fabrication methods should not simply be related to the
choice of material, but, also to the expectation of acceptable overall biocompatibil-
ity of the surface contacting the biological environment. As in the case of material
selection, some guidance on fabrication selection vis-`a-vis biocompatibility has
been included:
(a) Based on material selection and surface contacting exposure, select fabrication
methods which would tend to not compromise the overall biocompatibility of
the BioMEMS,
(b) If a hard” fabrication method must be employed, ensure that the final clean-
ing of the device removes all toxic residues or a secondary biocompatible
layer is bonded at the contact surface to prevent associated toxicity, without
impairing the overall activity of the BioMEMS,
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