There are three main types of biochips that have emerged since the
1990's. These include: plate-based DNA arrays, gel-based DNA arrays, and microfluidic biochips.
Plate-Based and Gel-Based Arrays
Both the plate based and the gel-based arrays use
essentially the same principles to acheive the same end result. Using a large substrate such as a glass plate or porous gel,
the biochips probes are immobilized. These probes are a large set of nucleic acid strands, each carrying a known genetic
sequence. The strands are embedded perpendicular to the plate and form a rectinlinear matrix (an array)(see
figure 1). A test sample is applied. Hybridization then
occurs at a few sites in the matrix. The results of the biochip readout are basically a list of the events that have taken
place. Each event plays an important role in determining a short span of an unknown coded region of DNA. At this pont
the location of this span of DNA is not known. This is why the probes were selected specially for testing the overlap
in the sequences. This way the identity of the full sequence can be determined easier, once the hybridization information
is arranged for maximum overlap. This is done by specialized computer software.
A DNA-array biochip does not conduct actual sequencing
reactions. Instead, it can test for many variations of the normal gene itself by focusing in on a specific gene.
There is yet another way in which genes can be examined and
analyzed. This method includes probing gene expressions patterns throuhout the genome. This time the probes are
not chosen to cover the whole length of the gene but instead they are chosen on the basis of having sequences
characteristic to different genes. These are called partial sequence tags.
"Whenever a gene is active, its code is transcribed into single-stranded messenger RNAs,
through which the gene transmits its instructions for cellular biosynthesis of a specific protein". So therefore a variety
of messengers end up in a cell's cytoplasm, depending on which genes are working at that point in time. Patterns
can then be seen when the messengers hybridize with one or another partial sequence tag on a biochip.
The testing may be made possible by "representational difference analysis", in which
results from two tissue samples are compared. The active genes in one sample are shown by subtracting one set of results from
the other. This also shows which genes are less active or completely inactive in the other sample. For example, normal
and cancer cells as well as metastatic and nonmetastatic cancers can be compared. By doing this comparison an abnormal
cellular process occuring in diseased cells may be identified.This way of testing may also help in identifying therapeutic
targets as well as helping in diagnostic testing.The "HyX Gene Discovery Modules now being manufactured by HySeq test simultaneously
for expression of 30,000 to 50,000 genes".
Gel-based arrays have the potential to be used for more than just DNA applications. One application
that is being put into place as we speak is the process of making a protein array. This protein array will be designed
to analyze an enzyme's activity, "or a drug's interaction with intended (and unintended) targets, or an antibody's specificities".
This analyses could be a huge help in diagnostic testing as well as drug development.
