What Every Cell Knows

By Mike May|Tuesday, September 01, 1992
After you first visit a doctor to find out what’s ailing you, a long time can pass before you receive the results of laboratory tests designed to identify your assailant. It could be a day, it could be a week, but it always seems longer. During all this agonizing and waiting, moreover, your body already knows, in a sense, what ails it. Your cells are responding to the presence of too much hormone, or they’re being subverted by a virus, or they’re being poisoned by bacterial secretions. If we could only detect pathogens the way a cell does, we would be one step closer to beating them.

It is an idea that the Biocircuits Corporation of Burlingame, California, thinks it can soon make a reality. Working with technology conceived in part at the Lawrence Berkeley Laboratory, Biocircuits is developing a biosensor, modeled loosely on the membrane of a human cell, that would analyze blood or urine for a virus or hormone and produce results within 15 minutes. Instead of being sent out to a clinical laboratory, the sample would be analyzed right in the doctor’s office-- saving the patient not only the worrisome delay but also, perhaps, the expense of a second visit to the doctor.

The Biocircuits biosensor has two key components. The first is made up of protein molecules, the same cell-surface receptors or antibodies that would naturally bind to the target substance in the human body. The second component is a film to which the proteins are attached, much as proteins are attached to the membrane of a cell. Like a cell membrane, the film is made of fatty substances called lipids, but in this case the lipids are bound together in a polymer.

To build the biosensor, the researchers pour a mixture of all these molecules on water. The molecules ride on the surface like a film of soap and assemble themselves into an ultrathin layer about one-millionth of an inch thick. (There’s more to the manufacturing process than that, certainly, but Biocircuits, fearful of competition, is keeping the details secret.)

In the past, one sticking point in designing artificial membranes has been getting the proteins to adhere to the membrane without losing their biological activity. In Biocircuits’ biosensor the lipids provide a natural and congenial environment for the proteins, while the polymerization gives the film its strength. Polymerization also makes the film highly fluorescent, a property that allows it to readily reveal the presence of the target substance.

The film is packaged in a disposable plastic cartridge about the size of a credit card. To run a test for, say, a hormone, a technician places a drop of blood or urine in a test well on the cartridge, then inserts the cartridge into an automated measuring instrument. Hormone molecules in the sample bind to the receptors on the film; they are in turn grabbed from the top by another protein, an antibody, that is included in the cartridge. The creation of these three-molecule chains distorts the structure of the film, and that causes the fluorescence emanating from the film to fluctuate in frequency. The precise fluctuation depends directly on the number of hormone molecules in the sample. Inside the measuring instrument, a light-emitting diode shines on the film, and a photodiode records the fluctuating fluorescence. The hormone’s concentration is displayed in about 15 minutes.

So far Biocircuits has built a prototype biosensor that tests for thyroid hormones. It plans to begin selling that device to doctors in 1993 for about $2,500, and to follow it in 1994 with a test for chlamydia, a sexually transmitted virus. But the company regards those plans as only its first steps into the huge medical testing market. In principle the Biocircuits technique could be applied to any number of pathogens; to adapt the biosensor to a different target, the company’s researchers simply have to synthesize the natural receptor for that pathogen and incorporate it in the film. Step-by-step and disease-by-disease, Biocircuits (along with other companies in the burgeoning biosensor business) may soon bring to medical testing some of the intelligence of the living cell.
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