Mason Inman - science journalist

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Molecular logic gates help sort cells

9 September 2006, for New Scientist

How do you colour-code a whole bunch of different objects using only one colour?

It sounds impossible, but researchers hoping to tag cells with combinations of fluorescent dyes have done just that.

They used a form of "molecular computing" that means similar dyes can be distinguished and so can be combined in myriad unique ways, allowing researchers to tag every cell in a huge population with a different label. The tags could also help nanotechnologists keep track of thousands of nano-devices.

To create the tags, chemist A. Prasanna de Silva at Queen's University, Belfast, UK, attached a variety of fluorescent dye molecules to 100-micrometre polystyrene beads, roughly 10 times the size of a human cell. Each dye molecule acts like a digit in a code, and to read this code, each of the dyes must be easily identifiable by the colour of its fluorescence.

In practice, many dyes fluoresce at similar wavelengths, limiting the possible combinations, so de Silva and colleagues devised a way to differentiate such dyes by the way they respond to various chemical conditions. For example, adding an acid might stop one dye molecule fluorescing, while a salt will switch off another. The fluorescing tags can be easily detected and analysed using a light sensor and processor.

The team says this makes the tags act like logic gates, the basic building blocks of computers, which produce different outputs according to what input signal they receive. One molecule could act as a YES gate, turning on in the presence of an acid, while another might behave as a NOT gate, switching off when bathed in the same chemical. "Instead of typing something on a keyboard, we throw chemical signals at the molecular computing device," he says. "Then the molecule replies to us. Rather than printing out the characters, it gives out a light signal."

He and his colleagues tested the idea using several dye molecules that all fluoresce in the same colour. When dipped in an acidic solution and then an alkaline one, each molecule reacted differently. This means previously indistinguishable dyes can now be combined to create huge numbers of unique codes for tagging cells (Nature Materials, DOI: 10.1038/nmat1733).

"The study shows that molecular computation can find real applications today," says chemist Vincenzo Balzani of the University of Bologna in Italy. It demonstrates an application for molecular computing that is possible but which no one had thought of, he says.