Synthetic Chemistry and Microelectrode Arrays for Point of Care Diagnostics

Molecular diagnostics typically require a molecular interaction that identifies a specific target, a device that detects, quantifies, and records that interaction, and an interface between those two elements. Each feature is critical for the success of the device. Yet while the first two are matters of intense interest an research, the surface itself is often ignored. This is problematic because it provides the platform for the whole "experiment". For a "point-of-care" diagnostic, the surface on the device must be stable both in terms of chemistry and time while still allowing the signal from the molecular interaction to be sensed and recorded. With this in mind, we have been focusing on the use of diblock copolymers as molecular surfaces for the construction of "point-of-care" diagnostics. We have developed a toolbox of chemical reactions that can be used site-selectively on such surfaces, and we have recently demonstrated that the approach taken is compatible with the use of DNA-aptamers to do multiplex sensing on a high density microelectrode array using a surface that is stable for a year. We have also illustrated how the quality of the signaling study conducted on an array is dependent on optimization of the chemical reaction. But exactly how good are the chemical reactions employed on the arrays to build a surface in a site-selective manner? One can tell with the use of fluorescence based studies that reactions happen where you want then to happen, but are there background reactions that can be problematic for a multiplex sensing experiment, do the reactions happen in high yield, and how much of an expensive, difficult to obtain biological reagent might be lost due to the confinement strategy? Are some reactions better than others in this regard? In short, if we are to optimize the surfaces constructed on a diagnostic device, then we need not only have tools in place for conducting synthetic chemistry on the device, but also the tools in place necessary to analyze those reactions. Understanding the chemistry that can and/or does occur at any electrode in a high density array requires more than looking at pretty pictures of fluorescent spots. In the talk to be given, we will utilize a combination of a "Kenner-safety-catch" linker strategy and molecular biology techniques to answer key questions about the synthetic chemistry used to construct the DNA-aptamer based multiplex sensor mentioned above.