Biochips – fundamentals and applications - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 370

using channels cut in a glass or plastic chip, instead of capillary tubes. Microfabricated
chip-based sequencers have many advantages over previous CE systems. The photolithog-
raphy techniques used to create these microchannels facilitate the addition of numerous
capillaries, making ultra-high lane densities - providing greater throughput capabilities
than capillary sequencers. The intricate enclosed microchannels set in glass or fused sil-
ica substrates enable ultra-fast DNA separations because of simplifi ed sample loading
procedures, short separation distances, and optimal thermal characteristics. Precise opti-
cal positioning across an array of microchannels simplifi es the detection process. And
integration of sample handling and analysis reduces human interference, permitting auto-
mation and further contributing to low operating costs. Many other approaches have been
tried, and new technologies are being developed, but none are likely to displace micro-
fabricated chip-based electrophoresis systems as the most probable future technology for
sequencing. Besides its promise for high throughput DNA sequencing, a microchip-based
CE system is also being exploited for nucleic acid and protein analyses such as separa-
tion, sizing, quantifying, and identifying DNA and RNA samples. CE microchips have
also been developed for rapid detection of single polynucleotide polymorphisms (SNPs)
in the human genome. In this post-genomics era, the refi nement of multiple channel
microchip-based CE devices and integrated process automation will undoubtedly estab-
lish this technology as a powerful high throughput tool for invaluable genetic analyses.
The possibility of building a complete DNA sequencing system on one integrated chip
is very real. Such a chip can include the DNA preparation, loading the separation matrix,
loading the sample, electrophoretic separation, and fl uorescence detection - all on a
single chip. Also, this chip can be mounted inside a computer like a PC board.
11.6 REFERENCES
1. B.F.C. Clark, Towards a total human protein map. Nature 292 , 491-492 (1981).
2. J.P. Jing, J. Reed, J. Huang, X. Hu, V. Clarke, J. Edington, D. Housman, T.S. Anantharaman, E.J. Huff,
B. Mishra, B. Porter, A. Shenkeer, E. Wolfson, C. Hiort, R. Kantor, C. Aston, and D.C. Schwartz,
Automated high resolution optical mapping using arrayed, fl uid-fi xed DNA molecules. Proc. Nat. Acad.
Sci. 95 , 8046-8051 (1998).
3. C.M. Li, V.E. Choong, S. Shi, and G. Maracas, Method for enhanced bio-conjugation events. US Pat
6,602,400 (2003).
4. C.M. Li and B. Chui, P450 single nucleotide polymorphism biochip analysis. US Pat 20040229222 A1
(2004).
5. M. Schena, D. Schalon, and R.W. Davis, Quantitative monitoring of gene expression pattems with a com-
plementary DNA microarray. Science 270 , 467-470 (1995).
6. L. Wodicka, H. Dong, M. Mittmann, M.H. Ho, and D.J. Lockhart, Genome-wide expression monitoring
in saccharomyces cerevisiae. Nat. Biotechnol. 15 , 1359-1367 (1997).
7. N. Zhao, H. Hashida, N. Takahashi, Y. Misumi, and Y. Sakaki, High-density cDNA fi lter analysis: a novel
approach for large-scale, quantitative analysis of gene expression. Gene 156 , 207-213 (1995).
8. M.J. Heller, A.H. Forster, and E. Tu, Active microelectronic chip devices which utilize controlled elec-
trophoretic fi elds for multiplex DNA hybridization and other genomic applications. Electrophoresis 21 ,
157-164 (2000).
9. V.G. Cheung, M. Morley, F. Aguilar, A. Massimi, R. Kucherlapati, and G. Childs, Making and reading
microarrays. Nat. Genet. (Suppl.) 21 , 15-19 (1999).