Biochips? computer chips attached to and somehow controlling living cells? have existed in the imaginations of science-fiction writers for years. Thus, it was perhaps understandable that research by Professor Stephen Boxer and graduate student Jay Groves, chemists at Stanford University, in collaboration with Stanford electrical engineer Nick Ulman, would cause a degree of excitement in the popular press. These scientists were successful in inducing phospholipid bilayers to stick to well-defined regions, which they called corrals, on appropriately treated wafers of silicon oxide–the same material used to make computer chips.

A phospholipid is a molecule that consists of a polar head group and two hydrocarbon “tails” tethered in ester linkages to a glycerol scaffold. A common example of a phospholipid, and one used by the Stanford chemists, isphosphatidylcholine (PC).

Phospholipids, when suspended in water, spontaneously form bilayers in which the polar head groups are oriented towards, and interact with, the solvent water. In addition, the hydrocarbon tails are oriented towards each other, away from the water. The driving force for this self-assembly process is the avoidance of energetically unfavorable hydrocarbon-water interactions–the same reason that oil and water don’t mix–as well as the favorable interactions between water and the polar head groups. 

Cell membranes, the envelopes of living cells, consist largely of phospholipid bilayers along with a few other associated molecules, such as proteins and steroids. The essential chemical character of cell membranes, however, is defined by the phospholipid bilayers.

Using photoresist techniques, the Stanford scientists laid out a grid pattern on silicon oxide wafers that allowed them to deposit phospholipid bilayers in regions, calledcorrals, separated by barriers of gold or aluminum oxide. The silicon oxide interacts favorably (by hydrogen bonding) with a 10-A-thick layer of water molecules, which, in turn, interact favorably with the polar head groups of a phospholipid bilayer. The water serves as a “glue” that holds the phospholipid onto the surface of the chip. This arrangement, they found, was stable to repeated washings.

The Stanford scientists demonstrated success in achieving the corral structure by including within the phospholipid bilayers a fluorescent dye; when the wafers were illuminated, only the corral regions fluoresced. Corrals as small as 5 micrometers x 5 micrometers (50,000 A x 50,000 A) could be observed. (This means that each corral has a few thousand phopholipid molecules on a side.)

The Stanford group believes that incorporation of appropriate receptor molecules into the supported membranes could lead to the binding of specific types of cells or viruses. In other words, it might be that cells or viruses might be tricked into binding to the supported membranes as if they are cells. This could lead to new, rapid methods of cell screening. Imagine, for example, that researchers could rapidly screen a blood sample for HIV particles by measuring changes in light emission or electrical forces that occur when the virus particles bind to the phospholipid bilayer. The question is whether or how the binding can be signaled to the underlying chip.

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