Biochips – fundamentals and applications - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 345

a sequence of process steps to fabricate silicon wafer-based microarray devices [109].
However, the fabrication of the electronic biochip comes only partly from semicon-
ductor fabrication technology and some specifi c fabrication process for micromachin-
ing, assembled together in a given order to produce a physical structure in the range of
micrometers to millimeters, has to be developed to meet detection requirements of the
biomolecular interaction. Printed circuit board (PCB) and screen-printing technology
have been exploited to fabricate low cost electronic biochips.
Batch fabrication is essential during research and optimization of the biochips. Such
batch processing can make thousands of identical devices not subject to the variations
present in individually constructed objects. Another application that well illustrates the
advantages of batch processing is nucleic acid arrays fabricated by photolithography.
For an n

n nucleic acid array, there are n 2 different oligonucleotides of length l .
Synthesizing each oligonucleotide individually would require n 2 l chemical steps.
Lipshutz et al. 's method [11] uses selectively masked photochemistry to synthesize the
oligonucleotides. It requires four chemical steps (one for each base) per unit length, or
4 l steps irrespective of the number of different oligonucleotides. Thus, one can make
a 4

4 array of octamers as easily as a 200 200 array. This dramatically decreases

the diffi culty of making large arrays.
Geometrical control can be very important for microstructures. Photolithography
allows one to pattern largely varying geometries (1

1 cm) in the same space
with micrometer dimensional accuracy. In addition, one can vary dimensions of
the same feature on a mask, instantly making tens of different but similar structures.
Often all one needs is a small constrained geometry, such as a small well. Constrained
geometries can be used to confi ne either proteins or mechanical forces for preventing
diffusion out, increasing a protein's local concentration. This is cleverly exploited by
applications involving electrochemical or optical probing of proteins in small wells. The
advantages of confi ning forces are well illustrated by the work of several investigators.
Using cell-sized chambers microfabricated in glass cover slips, Holy et al . examined
the assembly of microtubules (MTs) from artifi cial MT-organizing centers consisting
of tubulin-covered beads. In these constrained geometries, results showed that MT
polymerization alone could position the artifi cial MT-organizing centers in the middle
of the well, suggesting that these forces are important when considering MT dynamics.
Another study [110] used shallow channels with MTs attached to the bottom surface.
By looking at MT bending as it polymerized and hit the wall of the channel, they could
determine its force-velocity relationship. Both of these experiments would not work in
free solution; microfabricated constrained geometries enable the experiments.
The electronic biochip is composed of arrayed pairs of working electrodes and
counter electrodes. The detection scheme between fl orescent and electronic bioarray
is totally different; an optical scanner can have images for all arrayed spots in min-
utes, but electronic detection should be conducted one by one through multiplexing.
Thus, it is essential to make an electronically addressable bioarray, in which all arrayed
working and counter electrodes are fabricated in such a way that all working and coun-
ter electrodes are electronically connected in row (x) and column (y), respectively, as
shown in Fig. 11.27. During measurements, any pair of working/counter electrodes can

µ m to