Biomedical Engineering Reference
In-Depth Information
forces induced by high frequency alternating, rotating or traveling electric fi elds can
be used to levitate and/or to move cells in weak electrolyte solutions. Counting red
blood cells is a well-established method, but design of micromachined cell or particle
counters needs to be further investigated. It is possible to count cells by the change in
the electric resistance of a conducting fl uid if a cell of different conductivity passes.
A Coulter counter, where the change of the electrical resistance of a liquid fi lled capillary
is measured when a cell fl ows through, has been made as a microsystem. Cell sorting
and counting systems-based LOCs have good reproducibility and resolutions down to
a cell size of 0.6
M diameter [175]. Much work has focused on replacing the con-
ventional fl ow chamber with microfabricated devices and it has been shown that cells,
particles, and reagents can be manipulated by pressure, dielectrophoresis, and elec-
troosmosis [176-180]. Several groups have demonstrated on-chip detection by means
of impedance [178], fl uorescence [179], and laser-based spectroscopy [180]. Optical
forces have been reported in use for rapid (2-4 ms), active control of cell routing on a
microfl uidic chip [181]. The optical switch controls reduce the complexity of the chip
and simplify connectivity. Using all-optical switching, a fl uorescence-activated micro-
fl uidic cell sorted and evaluated its performance on live, stably transfected HeLa cells
expressing a fused histone-green fl uorescent protein.
µ
11.5.4.2 Combinatorial synthesis for drug screening
and materials discovery
The combinatorial synthesis approach is a powerful, yet simple, way to construct a large
number of compounds in a very small area in a very short time. For example, by going
through 32 iterations of oligonucleotide synthesis, scientists can produce all 65 536 oli-
gos containing eight units in about one day. Each of these compounds is contained within
a well-defi ned area on a microarray or biochip. Similarly, the combinatorial approach can
be used with peptide synthesis to create an assortment of peptides of almost any length.
Moreover, the combinatorial approach is not limited to oligonucleotides and peptides,
and there is considerable potential for combining a limited array of combinatorial prod-
ucts with microsampling techniques and microseparations to create automated organic
chemistry synthesizers, which will be very useful for drug discovery. Today, the drug
industry has rethought its combinatorial strategies and focuses instead on limited librar-
ies of up to several hundred compounds. This “rational design” of new drugs relies on
techniques that use information about a molecule's shape, size, electronic topology, and
lipophilicity or hydrophilicity to design a few, select, lead compounds. After testing these
leads, chemists systematically alter the candidate molecules until the desired activity is
optimized, generating thousands of candidates in a combinatorial library. Products have
resulted from combichem/microsynthesis, and the list continues to grow. In the pharma-
ceutical/biotech arena, lead compounds for the treatment of Alzheimer's disease, tuber-
culosis, and infl ammatory disorders are in the pipeline. Combinatorial drugs for pain,
cancer, multidrug resistance in cancer cells, HIV, lupus, and asthma are in clinical trials.
Unfortunately, rational approaches do not work with all types of chemistry. The rational
approach has achieved fewer successes in materials discovery than in pharmaceuticals.
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