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Analytical Chemistry

Tagging Based On Molecular Logic

Fluorescent-dye tags identify members of large populations of small objects

by Michael Freemantle
September 11, 2006 | A version of this story appeared in Volume 84, Issue 37

Credit: Michael Freemantle/C&EN
Credit: Michael Freemantle/C&EN

Fluorescence-based molecular logic gates can be used to generate millions of distinct tags for encoding nano- and microscale objects, according to chemists in the U.K.

The technique, dubbed molecular computational identification (MCID), is the molecular equivalent of radio-frequency identification (RFID). "MCID takes the baton from the popular RFID technology," which fails for objects less than about 1 mm in size, says A. Prasanna de Silva, chemistry professor at Queen's University, Belfast, Northern Ireland. He developed the MCID technique with colleagues in Belfast and at Avecia in Manchester, England (Nat. Mater., DOI: 10.1038/nmat1733).

The team tagged polymer beads, about 100 µm in diameter, with fluorescent dyes that act as molecular logic gates. The simplest system uses a blank and three dyes, each of which is a single logic gate with one chemical input [0 (off) or 1 (on) in binary logic], and one fluorescence output [0 (off) or 1 (on)] in a chosen color. For a given emission color, excitation color, and chemical input (protons, for example), the blank and dyes provide four logic tags (0 0, 0 1, 1 0, and 1 1).

"The only requirement is that the beads can be 'washed and watched,' " de Silva explains. "To identify a bead, we first wash it in a solution, such as an acid, and watch its fluorescence. We then wash it with an alkali and watch its fluorescence again. The fluorescence output pattern tells us which type of logic tag is attached to the bead."

By employing different logic types in different combinations on the beads, different chemical inputs, and different excitation and observation wavelengths, it is possible to generate millions of distinguishable tags. "The final MCID tag address of a given object can be read sequentially just as we read a car number plate or an Internet Protocol address," for example, excitation wavelength, emission wavelength, logic type and combination, inputs, and binding threshold for each input, the authors note.

"This paper shows that molecular computation can indeed find real applications today," comments Vincenzo Balzani, professor of chemistry at the University of Bologna, Italy.

MCID could be used for the analysis of large combinatorial libraries of beads, such as those used in split-and-mix peptide library synthesis.

"Tags can be connected to the beads at each step when the amino acids are attached so that the synthesis history can be correlated with the ID tags," de Silva says. "The amino acid sequence on a given bead can then be determined without having to perform amino acid sequencing."

The MCID technique is not confined to logic gates that employ binary logic. "We are also able to use ternary logic of 0 (off), 1 (mid), and 2 (on), with, for example, output level 2 in acid and output level 1 in alkali," de Silva says. "The use of ternary and even higher valued logic in our application gives higher information density than binary logic can provide."



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