Biochip Technology

It is important to realize that a biochip is not a single product, but rather a family of products that form a technology platform. Many developments over the past two decades have contributed to its evolution. The very concept of a biochip was made possible by the work of Fred Sanger and Walter Gilbert, who were awarded a Nobel Prize in 1980 for their pioneering DNA sequencing approach that is widely used today. DNA sequencing chemistry in combination with electric current, as well as micropore agarose gels, laid the foundation for considering miniaturizing molecular assays. Another Nobel-prize winning discovery, Kary Mullis’s polymerase chain reaction (PCR), first described in 1983, continued down this road by allowing researchers to amplify minute amounts of DNA to quantities where it could be detected by standard laboratory methods. A further refinement was provided by Leroy Hood’s 1986 method for fluorescence-based DNA sequencing, which facilitated the automation of reading DNA sequence.  Read more about Bioinformatics Market Potential

Further developments, such as sequencing by hybridization, gene marker identification, and expressed sequence tags, provided the critical technological mass to prompt corporate efforts to develop miniaturized and automated versions of DNA sequencing and analysis to increase throughput and decrease costs. In the early and mid-1990s, companies such as Hyseq and Affymetrix were formed to develop DNA array technologies

DNA-based biochips are at present used primarily for two types of analysis.

• First, they have been used successfully for the detection of mutations in specific genes as diagnostic “markers” of the onset of a particular disease. The patient donates test tissue that is processed on the array to detect disease-related mutations. The primary example of this approach is the Affymetrix GeneChip. The p53 GeneChip is designed to detect single nucleotide polymorphisms of the p53 tumor-suppressor gene; the HIV GeneChip is designed to detect mutations in the HIV-1 protease and also the virus’s reverse transcriptase genes; and the P450 GeneChip focuses on mutations of key liver enzymes that metabolize drugs.

• A second application for DNA-based biochips is to detect the differences in gene expression levels in cells that are diseased versus those that are healthy. Understanding these differences in gene expression not only serves as a diagnostic tool, but also provides drug makers with unique targets that are present only in diseased cells.

Besides these two immediate array-based applications for this technology, a number of companies are focusing on creating the equivalent of a wet laboratory on a chip. One example is Caliper’s LabChip, which uses microfluidics technology to manipulate minute volumes of liquids on chips. Applications include chip-based PCR as well as high-throughput screening assays based on the binding of drug leads with known drug targets.

Finally, it is sometimes asked whether mass spectrometry can be part of next-wave biochip technology. Currently conceived biochips are essentially immobilized arrays of biomolecules, whereas mass spectrometry can determine molecular structure from ionized samples of material. Therefore, it is difficult to envisage a direct connection between the two, but perhaps in the future certain aspects of biochip analysis might be performed by mass spectrometry approaches.

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