Abstract: The small scale of nano-materials makes them one of the best man-made candidates to interact with biological systems at subcellular or even molecular level. It has been the focal point of the research interests to interfacing live cells with one dimensional nanostructures, such as nanowires and nanopillars. In my Phd research, I have utilized nanopillar based structures and devices to interface biological cells electrically, optically and mechanically. 1. We achieve improved electric interface between biological cells and solid state device by using arrays of vertically aligned nanopillar electrodes. Their tight attachment to the cell membrane allows us to acquire intracellular-like action potential signals non-destructively from cultured cardiomyocytes, which is responsible for various important cellular functions. 2. We demonstrate below-the-diffraction-limit observation volume in vitro and inside live cells by using vertically aligned silicon dioxide nanopillars. With a diameter much smaller than the wavelength of visible light, a transparent silicon dioxide nanopillar embedded in a nontransparent substrate restricts the propagation of light and affords evanescence wave excitation along its vertical surface. This effect creates highly-confined illumination volume that selectively excites fluorescence molecules in the vicinity of the nanopillar. We show that this nanopillar illumination can be used for in vitro single molecule detection with high fluorescence background. In addition, we demonstrate that vertical nanopillars interface tightly with live cells and function as highly localized light sources inside the cell. Furthermore, chemical modification of the nanopillar surface provides a unique way to locally recruit proteins of interest and simultaneously observe their behavior within the complex, crowded environment of the cell. 3. We engineer and fabricate vertically nanopillar arrays, and culture various types of cells atop. We study the cell growth pattern in presence of nanopillar arrays, including attachment, migration, etc. We also design patterned nanopillar arrays and utilized them to guide and control cell growth via cell-nanopillar interaction.