Amplifying Electrochemical Indicators

Ames Research Center, Moffett Field, California

Dendrimeric reporter compounds have been invented for use in sensing and amplifying electrochemical signals from molecular recognition events that involve many chemical and biological entities. These reporter compounds can be formulated to target specific molecules or molecular recognition events. They can also be formulated to be, variously, hydrophilic or amphiphilic so that they are suitable for use at interfaces between (1) aqueous solutions and (2) electrodes connected to external signal-processing electronic circuits. The invention of these reporter compounds is expected to enable the development of highly miniaturized, low-power-consumption, relatively inexpensive, mass-producible sensor units for diverse applications, including diagnoses of infectious and genetic diseases, testing for environmental bacterial contamination, forensic investigations, and detection of biological warfare agents.

The multiple functionality of a reporter compound of this type is achieved through integration of a variety of chemical moieties into each molecule. The structure and composition of such a molecule is depicted schematically in the figure and represented by the general formula ALBn. As used here, A signifies a targeting group, L signifies a linking group, and B signifies an active group.

A **Reporter Compound** according to the invention can have any of a wide variety of dendritic structures. The A, B, and L groups contribute synergistically to the overall effect of generating a highly amplified primary electrochemical sensory signal.

The targeting group (A) can include nucleic-acid intercalators or other organic functional subgroups. It is designed to interact directly with a targeted molecule or molecular recognition event; that is to say, it is designed to bring itself and the rest of the reporter molecule into the vicinity of the target. Hence, the collective effect of the targeting groups of multiple reporter molecules is to concentrate the reporter compound in the region of the target compound or molecular recognition events that one seeks to detect. An active group (B) is, more specifically, either (1) electroactive in a manner that enables detection of an electrochemical signal or (2) hydrophilic to enhance solubility. It is preferable that the number (n) of B groups exceed 1. The linking group (L) comprises two moieties: (1) a linker between the targeting (A) group and the B groups and (2) an amplifying moiety, through which the B groups are connected in series, parallel, or a combination of series and parallel connections in a dendritic structure.

The active (B) groups can also be characterized as indicator groups because these are the ones that generate the desired electronic sensory signals. Because they are linked to the targeting group, the active groups are concentrated in the vicinity of the target, and the probability that each will generate a signal is correspondingly increased. The multiple active groups, connected together in the dendritic molecular structure, contribute to an aggregate signal much greater than that generated by a single-indicator reporter molecule. Depending upon the specific formulation of a reporter molecule according the invention, the primary signal could be as little as two times or more than a thousand times as great as that generated by a single-indicator reporter molecule. By increasing signal-to-noise ratios relative to those available from prior reporter compounds, the invention of these reporter compounds can be expected to facilitate the detection of very small amounts of target compounds — for example, particular genes in blood samples.

This work was done by Wenhong Fan, Jun Li, and Jie Han of Ames Research Center. For further information, access the Technical Support Package (TSP) free online at www.techbriefs.com/tsp under the Materials category.

Inquiries concerning rights for the commercial use of this invention should be addressed to