The first objective of the proposed research program is to develop a fabrication technology that improves the reliability of tetrodes and supports the development of 3-dimensional electrical probes with ten to a hundred channels. The approach is to define integrated electrode arrays on the surface of a fine tapered needle that can penetrate the brain with minimum damage. The diameter of each of the 4 contacts at the 40 μm tip of the new design will be about 15 μm. The contact resistance of an electroplated gold contact of this diameter is 300-500 thousand ohms, a very large value that significantly degrades the signal-to-noise ratio of the recordings. A solution requires increasing the area of a contact without increasing its physical size; our approach will be to fabricate a dense array of high aspect ratio gold pillars ~50 nm in diameter pillars on the contact. The second objective is to develop a multimodal probe that will, for the first time, link the underlying neuronal electrical activity with the associated changes in the biochemical microenvironment near the probe tip. The neuronal activity is modulated by the local biochemical environment, and at the same time, the activity releases neurotransmitters and initiates cascades that change the local environment The approach will be to add a surface enhanced Raman scattering (SERS) sensor at the probe's distal end. In addition, compositional information of the local brain tissue, i.e., a volume ~1000-10000 μm3, can be simultaneously obtained by Raman spectroscopy that does not rely on the surface enhancement effect. An integrated lightguide on the side of the probe will deliver excitation light to the distal end of the probe and return Raman·scattered light to a spectrograph-detector assembly outside the brain. A high-density array of gold columns will be fabricated at the lightguide exit and provide surface enhancement. In addition to expertise in optical design and instrumentation, the Co-PI (WCS) has developed extensive chemometric techniques for extracting quantitative information of specific biochemical analytes. The approach to fabricating the electrical contact, integrated lightguide, and SERS nanostructures is atom beam proximity lithography where a stencil mask is illuminated with a broad beam of energetic helium atoms and transmitted beamlets transfer the pattern to resist on a substrate. The technology, coupled with a unique conformal resistant deposition process, has the unique capability of fabricating 50 nm structures on a needle at distances up to 2.5 millimeters from the mask. The use of neutral particles, instead of ions or electrons, ensures that minute electromagnetic fields will not distort the atom beamlets, whose aspect ratio can exceed 50,000:1. The PI(JCW) developed the critical source, mask, resist, and exposure technology with prior NSF support. A proven fluorescence-based alignment technique will be used to register the various layers of the integrated probe.