Complementary Electrical and Spectroscopic Detection Assays with On-Wire-Lithography-Based Nanostructures

摘要

The ability to sensitively detect biomolecules and monitor complex biological processes has enabled many important fundamental and technological advances in the life sciences.~[1] These include novel and powerful ways of diagnosing disease, pharmaceutical screening procedures,and a variety of biosafety applications.~[2–4] Over the past couple of decades, a number of different detection methods have been developed for highsensitivity biomolecule detection.~[5–19] Many of these rely on nanostructures with novel signal transduction or signal amplification modes. Most can be categorized either as spectroscopic~[5–11] or electrical approaches~[12–17] and have strengths and weaknesses depending upon the analyte, environment, and intended uses.~[1–3] With researchers gaining increasing control over the architectural parameters of nanostructures, one can begin to envision systems with multiple layers of complexity and corresponding functional capabilities. Electrical approaches are attractive because in principle they can be miniaturized in the form of relatively simple and even portable devices.~[13,14,17] Spectroscopic approaches often rely on an additional labeling material and have the virtue of offering greater amounts of chemical information about the analytes being probed.~[6,8] The combination of these two assay formats within the context of a single nanostructure can provide built-in internal assay controls~[20] and a way to independently measure multiple steps in a complex biological process. Herein, we describe how one can use segmented nanostructures~[21–25] prepared by on-wire lithography (OWL)~[23,24] to create a system with two orthogonally functional components: one that behaves as a diode-like detection system with electrical readout, and the other that acts as a Raman enhancing device that allows one to spectroscopically probe different but related reactions that occur on the same device (Figure 1A).