Synthetic Chemistry and Microelectrode Arrays: Building Stable Platforms for Point of Care Diagnostics

Abstract

Molecular diagnostics typically require three main components. A molecular interaction that identifies a specific target, a device that detects, quantifies, and records that interaction, and an interface between the two. The interface is critical because it provides a means to fix molecular recognition elements to the surface of the device. For a "point-of-care" application, the interface must be stable both in terms of chemistry and time while still allowing the signal from the molecular interaction to be sensed and recorded by the device. For the use of a microelectrode array as the detection device, construction of the interface must also allow for individual molecular recognition elements to be placed by individual, addressable electrodes in the array.Because of the need for stability and synthetic flexibility, we made the choice to move away from the use of self-assembled monolayers as the interface for developing microelectrode arrays as point-of-care devices. To that end, we have employed diblock copolymers to coat the surface of microelectrode arrays, a change that has offered increased stability of the surface and enabled the use of a broad array of synthetic methods for functionalizing the electrodes in the array. In this talk, we show how the use of a diblock copolymer in conjunction with Cu(I)- and Cu(II)-mediated reactions can be used to functionalize a microelectrode array with multiple DNA-aptamers for the multiplex detection of metabolites. The resulting surface is stable for over 30 weeks (and counting), allows for the detection of multiple metabolites in the same experiment, and retains the detection sensitivity obtained with a self-assembled monolayer.One of the goals of the talk will also be to illustrate for the synthetic community the role that it can play in developing new tools for molecular diagnostics. After all, it is the surface on a microelectrode array that in the long-run defines what an array can be used for and the quality of the resulting analytical experiments. The construction of those surfaces is a synthetic chemistry challenge that moving forward will require both new synthetic methods and new approaches for characterization of the products generated from the new methods. One approach for characterization will be discussed in the context of the Cu(I)- and Cu(II)-mediated reactions employed in the current study.