DNA CHIP / DNA MICROARRAY

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" THE MOST ADVANCDED COMPUTING OPTION "

It is widely believed that thousands of genes and their products (i.e., RNA and proteins) in a given living organism function in a complicated and orchestrated way that creates the mystery of life. However, traditional methods in molecular biology generally work on a "one gene in one experiment" basis, which means that the throughput is very limited and the "whole picture" of gene function is hard to obtain. In the past several years, a new technology, called DNA microarray, has attracted tremendous interests among biologists.


This technology promises to monitor the whole genome on a single chip so that researchers can have a better picture of the interactions among thousands of genes simultaneously. Terminologies that have been used in the literature to describe this technology include, but not limited to: biochip, DNA chip, DNA microarray, and gene array. Affymetrix, Inc. owns a registered trademark, GeneChip which refers to its high density, oligonucleotide-based DNA arrays. However, in some articles appeared in professional journals, popular magazines, and the WWW the term "gene chip(s)" has been used as a general terminology that refers to the microarray technology.


Base-pairing (i.e., A-T and G-C for DNA; A-U and G-C for RNA) or hybridization is the underlining principle of DNA microarray. An array is an orderly arrangement of samples - provides a medium for matching known and unknown DNA samples based on base-pairing rules and automating the process of identifying the unknowns. An array experiment can make use of common assay systems such as microplates or standard blotting membranes, and can be created by hand or make use of robotics to deposit the sample. In general, arrays are described as macroarrays or microarrays, the difference being the size of the sample spots. Macroarrays contain sample spot sizes of about 300 microns or larger and can be easily imaged by existing gel and blot scanners. The sample spot sizes in microarray are typically less than 200 microns in diameter and these arrays usually contains thousands of spots. Microarrays require specialized robotics and imaging equipment that generally are not commercially available as a complete system. DNA microarray, or DNA chips are fabricated by high-speed robotics, generally on glass but sometimes on nylon substrates, for which probes with known identity are used to determine complementary binding, thus allowing massively parallel gene expression and gene discovery studies. An experiment with a single DNA chip can provide researchers information on thousands of genes simultaneously - a dramatic increase in throughput. There are two major application forms for the DNA microarray technology:

(1) Identification of sequence (gene / gene mutation); and
(2) Determination of expression level (abundance) of genes.

There are two variants of the DNA microarray technology, in terms of the property of arrayed DNA sequence with known identity:

Format I : probe cDNA (500~5,000 bases long) is immobilized to a solid surface such as glass using robot spotting and exposed to a set of targets either separately or in a mixture. This method, "traditionally" called DNA microarray, is widely considered as developed at Stanford University.

Format II : an array of oligonucleotide (20~80-mer oligos) or peptide nucleic acid (PNA) probes is synthesized either in situ (on-chip) or by conventional synthesis followed by on-chip immobilization. The array is exposed to labeled sample DNA, hybridized, and the identity/abundance of complementary sequences are determined. This method, "historically" called DNA chips, was developed at Affymetrix, Inc. , which sells its photolithographically fabricated products under the GeneChip trademark. The microarray (DNA chip) technology is having a significant impact on genomics study. Many fields, including drug discovery and toxicological research, will certainly benefit from the use of DNA microarray technology.
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IBM DEEPEST BLUE SUPER COMPUTER APPLICATIONS

* GENE DISCOVERY : (Many, many applications, to be listed)

* DISEASE DIAGNOSIS : micro fluids Bioinformatics is now being recognised as providing almost the only rational way forward in the curing of virus diseases like HIV-AIDS and the future best-hope for the treatment of cancer. Until now, few individuals have had the necessary breadth of knowledge in all of these areas, limiting our ability to combine them with full affect.


* DRUG DISCOVERY : Pharmacogenomics - Why some drugs work better in some patients than in others? And why some drugs may even be highly toxic to certain patients? My favorite definition (modified): Pharmacogenomics is the hybridization of functional genomics and molecular pharmacology. The goal of pharmacogenomics is to find correlations between therapeutic responses to drugs and the genetic profiles of patients.

* TOXICOLOGICAL RESEARCH : - Toxicogenomics : Toxicogenomics is the hybridization of functional genomics and molecular toxicology. The goal of toxicogenomics is to find correlations between toxic responses to toxicants and changes in the genetic profiles of the objects exposed to such toxicants.

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WHAT THE FUTURE BEHOLDS ?

The commercialization of DNA-chip technologies may depend as much on overcoming regulatory and marketplace hurdles as on advancing technology. Despite the myriad applications for the DNA chips now being introduced to research markets, demand for this technology is still relatively small. Nevertheless, most observers agree that this situation will soon change, as DNA chips begin to show up in products designed for more-traditional clinical applications. The consensus of these experts is that clinical products involving DNA microarrays will begin to reach the marketplace sometime early in the next decade. To reach this point, however, several important regulatory and technical hurdles must be overcome. Because of the enormous challenges in meeting regulatory requirements and convincing clinicians and third-party payers of the cost-effectiveness of new DNA-chip; based testing, most observers do not expect these technologies to reach the clinical laboratory in significant numbers any time prior to 2003. "By 2010 or sooner absolutely believe that we will see instrumentation using DNA chips in point-of-care applications," says Farkas. DNA chips will bring about a sea change in the way that some of humankind's most vexing diseases are diagnosed and treated. In some cases they will make it possible to move diagnostics out of the clinical lab, where traditional tests might take several days to perform, to the point of care, where results involving the detection of minute quantities of diseased cells will be provided within minutes. The challenges facing manufacturers in bringing these technologies to the marketplace are enormous.