Biochips combine a triad of micro-electro-mechanical, biochemical, and photonic technologies

Biotechnology is often referred to as the technology of the 21st century. Cover stories reporting the potential impacts of recent progress in biotechnology have appeared in several journals and magazines, including Time, Business Week, National Geographic, R&D, and Forbes ASAP. In particular, biochips, which integrate conventional biotechnology with semiconductor processing, micro-electro-mechanical systems (MEMS), optoelectronics, and digital signal and image acquisition and processing, have received a great deal of attention.

The term "biochip" has taken on a variety of meanings. In the most generic sense, any device or component incorporating biological (or organic) materials -- either extracted from biological species or synthesized in a laboratory -- on a solid substrate can be regarded as a biochip. In practical terms, however, biochips often involve both miniaturization, usually in micro-array format, and the possibility of low-cost mass production. Some examples that meet these qualifications include the electronic nose or artificial nose chip, the electronic tongue, the polymerase chain reaction chip, the DNA micro-array chip (gene chip), the protein chip, and the biochemical lab-on-a-chip.The most dynamic investigations into biochips have been in the gene chip and the protein chip. In this article, I use the gene chip as an example to illustrate the interdisciplinary nature of this novel technology.

Figure 1. A schematic Illustration of a gene chip.

A gene chip refers to a two-dimensional array of small reaction cells (each on the order of 100 X 100 µm) fabricated on a solid substrate. The solid substrate can be a silicon wafer, a thin sheet of glass, plastic, or a nylon membrane. In each reaction cell, trillions of polymeric molecules from a specific sequence of single-strand DNA fragment are immobilized (Figure 1). The DNA fragments can either be short (about 20 to 25) sequences of bases (A, T, G, and C) or longer strands of complementary DNA (cDNA). The specific sequence of bases (for example, CTATGC...) in each cell is preselected or designed based on the intended application. The known sequences of single-strand DNA fragments immobilized on the substrate are often called the probes. When unknown fragments of single-strand DNA samples, called the target, react (or hybridize) with the probes on the chip, double-strand DNA fragments are formed where the target and the probe are complementary according to the base-pairing rule (A paired with T, and G paired with C). To facilitate the diagnosis or analysis of the hybridized chip, the target samples are often labeled with tags, such as fluorescents, dyes, or radio-isotope molecules. When the targets contain more than one type of sample, each is labeled with its own distinguishable tag. Depending on the size of the array, this kind of DNA micro-array chip provides a platform where the unknown target or targets can potentially be identified with very high speed and high throughput by matching with tens of thousands of different types of probes via hybridization in parallel.

The components involved in the research and development of biochip technology, and the associated technical disciplines are shown in Figure 2. Biochip technology is intrinsically interdisciplinary; a synergistic collaboration of scientists and engineers from different disciplines is essential to push this novel technology from a lab curiosity to practical devices and systems.

Figure 2. The components and the associated technical disciplines involved in the R&D of biochip technology.

Nearly all applications of biotechnology or genetic engineering that rely on information related to DNA sequences (or gene sequences) will benefit from the gene chip technology. Current research and development of gene chip technology has focused on applications such as prognosis or diagnosis of genetic diseases, drug design, testing of drug efficacy, toxicology, and genetic agricultural products. The market size is about $1 billion, with the pharmaceutical industry the primary user and biomedical research labs the secondary. Some project the market may grow to $40 billion in 2010, with hospitals and clinics the primary users and the pharmaceutical industry the secondary.

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