Biomedical Engineering Reference
In-Depth Information
be used for a measurement of difusion in a binding assay, for example. Because of their size,
microsystems can be homogeneously treated with chemicals, cleaned, and then coated with
thin ilms of well-characterized thicknesses; inherent in the fabrication process is a detailed
physicochemical knowledge of the materials that form each part of the device, which is essential
in tailoring biochemical coatings for cell attachment, implants, and enzymatic reactions in a
biosensor—very unlike the low-reliability instructions on sanding and priming that one needs
to follow to paint the exterior of a house with a durable coating. As a corollary of allowing for
quantitative design, microsystems yield quantitative measurements, and this is not only because
of the large numbers involved. For instance, in a traditional cell culture, the spacing between
cells and the average cell density cannot be controlled independently—we say that the vari-
ables are
confounded
—yet they are both important factors in cell behavior; on the other hand,
in a micropatterned cell culture in which the cells can be positioned at well-deined spacings,
the two variables can be varied independently—we say that they are
decoupled
. We shall refer
to the beneit derived from quantitative design and rich-statistics output as the
quantitative
beneit
.
What is the result of such beneits? As depicted in
Figure 1.1
, the small-scale beneit has
been most important in
building the fundamentals
, such as increasing the switching speed of
transistors and understanding the basic properties of cells and luids. he high-throughput ben-
eit, on the other hand, has been mainly important for
building applications
, such as integrated
circuits, engineered tissue scafolds, and lab-on-a-chip biosensing systems. hese beneits are by
no means exclusive: all three beneits added together promise to provide fundamental insights
into the variability of single-cell behavior—a paramount goal of systems biology, which aims
to yield a global understanding of cell physiology and disease. he high-throughput beneit
works together with the quantitative beneit to lower the
cost of fabrication
, and large numbers
and small-scale beneits cooperate to reduce the
cost of operation
(e.g., use of small amounts of
reagents in many channels in parallel). In addition, cost reduction is a key factor in enabling the
dissemination of BioMEMS—e.g., commercializable point-of-care diagnostic microdevices—
for the ultimate beneit of society.
It is important to recognize that this analogy between BioMEMS and microelectronics
should not be abused. Microelectronic devices deal only with electrons, fundamentally immu-
table entities, and their economy of scale has thus far obeyed the famous Moore's Law (according
to which the number of transistors per unit area increases exponentially, almost doubling every
year). In contrast, BioMEMS devices struggle to deliver, analyze, and measure a virtually ini-
nite variety of biomolecules whose function oten degrades with time. here is no transistor for
BioMEMS, and most likely, there will be no Moore's law for BioMEMS. If a technology choice is
based on the previous analogy, it is most likely not founded on solid scientiic principles.
1.2 From Art to Chips
Modern microfabrication technology is based on
photolithography
, the patterning of a layer of
photosensitive polymer (
photoresist
) by light. he use of photosensitive materials for pattern-
ing is not new. A myriad of photographic methods have been used in art-making, reproduction,
and printing since the nineteenth century, and they have all been derived from the discovery of
light-sensitive substances. Even before photography, in 1827, Nicéphore Niepce coated a copper
plate with bitumen (a light-sensitive natural tar), exposed it to sunlight through a waxed paper
containing an ink drawing, dissolved the unexposed ink-shadowed areas with benzene, and
transferred the pattern to the underlying copper plate using an acid etch. Later known as “photo-
engraving,” this process soon incorporated photographic ilm as exposure masks and more con-
venient, water-soluble substances, such as gelatin or egg whites, which were photosensitized by
the addition of potassium dichromate.
