Biochips Part 1

The S4MS chip is used for sensing oxygen or glucose. Light generated by the light-emitting diode (LED) causes the surrounding molecules to fluoresce. The light that emerges has a new wavelength, and only this light passes through the filter to be detected by the photodiode. Oxygen or glucose decreases the fluorescence of the molecules in the top reservoir.

Tuan Vo-Dinh's DNA biochip could revolutionize the way the medical profession performs tests on blood. The chip, for which a patent has been filed, will allow for instant test results for the AIDS virus, cancer, tuberculosis, and other diseases. Vo-Dinh, a member of ORNL's Life Sciences Division, expects the chip to also have environmental applications.

Within a few years, DNA micro arrays could help diagnose and treat cancer, perhaps even before tumors form.

In preparation for minor surgery, John Leventhal needed a routine chest X-ray. When the New Haven, CT, doctor joined the radiologist who was examining the film, he was shocked by what he saw: an opaque blotch deep in his lung. "As a physician," says Leventhal, "you're taught in medical school that when you see a mass like that, it means lung cancer."

Leventhal's medical training also taught him that to confirm the diagnosis, his doctors would need to crack open his rib cage to get a piece of the suspect tissue that would be closely examined by a pathologist-an extremely painful and hazardous operation.

The weekend before that surgery, Leventhal went off on a family ski vacation. He recalls thinking, "This is the last time I will go skiing for a long, long time."

That was five years ago. Today the medical profession's way of dealing with cancer could be about to change. Around the same time that Leventhal underwent surgery, researchers at Stanford University and Santa Clara, CA-based startup Affymetrix were beginning to build the first 'DNA micro arrays'.

More commonly known as DNA chips, these are DNA-covered silicon, glass, or plastic wafers capable of analyzing thousands of genes at a time to, for example, identify the ones that are active in a sample of cells.

Now these micro arrays appear poised to join the war on cancer. DNA chips, predicts the National Cancer Institute director Richard Klausner, are 'going to have a huge effect' on the diagnosis and treatment of the disease.

One reason for the excitement is that DNA chips offer a whole new and potentially much earlier, easier, and more precise way of detecting cancerous cells.

Most forms of cancers go unnoticed until lumps, coughs, or pains develop, at which point it is often too late. And even then, once a pathologist gets a biopsy from a tumor, distinguishing one form of cancer from another can be difficult with existing techniques, which involve noting distortions in the cells' architecture under a microscope.

Better diagnostic information could be used to make better treatment decisions, perhaps making the difference between life and death.

Within the next two years, pathologists expect to begin using DNA chip-based tools to spot genetic differences among cells; these telltale differences could be used to help detect cancerous cells long before symptoms develop and to distinguish one type of cancer from another.

In short, the chips will provide a genetic profile of a cancerous cell that can be read like a criminal's rap sheet. The physician will know where the cancerous cell originated, how far it has progressed, and which therapies will work best to halt its further growth and spread.

A DNA chip-based device might be able to read a sputum sample right in the doctor's office, checking for the genetic changes in the lung cells that are naturally sloughed off into the viscous fluid. If the news is bad, the patient might well have a host of new treatment options.

That's because DNA chips are also speeding the discovery of new and better cancer drugs. "We're on the threshold of a new era," says Klausner. "Technologies like DNA chips will tell us not only that something may be amiss, but what it is and what we can do about it."

Today, dozens of companies provide DNA-chip products and services. With the development of new ways to fabricate the chips, researchers now have the option of buying ready-made chips or building their own customized chips right in the lab.

New diagnostic techniques promise to put a powerful lab on a dime-sized slice of silicon.
In 1995, Breaker and his team began to resurrect this extinct 'RNA world' in a test tube and successfully engineered RNA-based molecular switches in the effort. (A molecular switch is a molecule that's turned on or off by another molecule or compound.)

With dozens of these switches on hand, Breaker thought, why not arrange them on a surface and create an array of biosensors that use RNA to measure or detect compounds?

By engineering the RNA switches to detect many different kinds of compounds, Breaker knew that the potential of his array could surpass that of a DNA chip, which identifies specific DNA or RNA sequences and nothing else.

To create the prototype, Breaker placed the RNA switches on a gold-coated silicon surface and arranged them in clusters. Each switch was designed to bind only to a specific molecule-its 'target'-and then to release a signal that identified the target molecule. (In the prototype, the switches released a radioactive signal.)

As reported in April's Nature Biotechnology, Breaker and his team tested the array of RNA switches on a variety of complex mixtures. In one experiment, they successfully identified different strains of E-coli found in bacterial cultures.

The implications are enticing. The array's ability to simultaneously identify a potentially large number of compounds, combined with the precise exclusivity of each switch, adds up to a recipe for a powerful and wide-ranging laboratory on a dime-sized slice of silicon.