By Jeremy Lateiner
A DNA chip (also known as a gene chip or DNA microarray) is a small, flat surface onto which DNA strands are immobilized. The DNA is immobilized in distinct spots, and each spot contains a unique DNA sequence. DNAs under investigation will bind to their complementary DNA sequence attached to the chip (a process called hybridization). Following the hybridization of complementary DNA sequences, the fidelity of this hybridization is analyzed with the use of phosphorescent chemicals that bind to the hybridized strands. The light produced by these chemicals is then scanned by a chip reader, and the position and relative intensity of the light spots is analyzed by a computer.
DNA chips were initially used for enhancing genome sequencing projects like the Human Genome Project. DNA chips now are finding applications throughout molecular biology. Gene scanning provides a rapid method to analyze thousands of genes simultaneously. DNA chips are thus potentially very powerful tools for gaining insight into the complexities of gene expression, detecting genetic variations, making new gene discoveries, genetic fingerprinting and developing new diagnostic tools.
Computer chips and DNA chips are similar in that they both hold very large amounts of data on a very small surface. The production of DNA chips involves nano- and microscale fabrication techniques. These techniques were originally developed for use in computer chip manufacturing and are now being used in DNA chip manufacturing. Recent scientific achievements have made possible the application of organic structures, such as segments of DNA and other biomolecules, to the surface of inorganic materials. However, unlike the silicon-based computer chips, DNA chips are manufactured out of glass or plastic wafers.
Not all DNA chips are the same. Although the fundamental principles of molecular biology are consistent in the design of all DNA chips, approaches to the fabrication of DNA chips vary considerably. Currently most developers use techniques very similar to those used in computer chip fabrication. The DNA chip manufacturer, Affymetrix, produces a DNA chip much like a computer chip, bonding hundreds of genetic sequences onto the surface of a microchip via techniques (like photosensitive masking) currently used in computer chip fabrication.
There are three basic types of DNA chips. The first, oldest and most commonly discussed is the sequencing chip. On sequencing chips, short segments of DNA are placed in a microarray. Target samples are then applied to the chip. The segment to which the sample adheres determines the result, or sequencing by hybridization (SBH).
The second kind of DNA chip is called the expression chip. These are designed to determine the degree of expression of a certain genetic sequence by measuring a tissue's utilization of that gene. These chips are useful in diagnosing diseases (like some forms of cancer) which exhibit a particular gene utilization pattern.
The third type of chip is the comparative genomic hybridization chip. This chip helps scientists determine the relative amount of a given genetic sequence in a particular patient. This type of DNA-chip is designed to measure the amount of a sequence in a healthy tissue sample for comparison it with tumor tissue. Doctors may alter the severity of an anti-cancer treatment program based upon the result of this kind of analysis, since a cancer which has more than the normal number of gene copies may be of a more malignant type.