Weiss leads an interdisciplinary research group which includes chemists, physicists, biologists, materials scientists, electrical and mechanical engineers, and computer scientists. Their work focuses on the atomic-scale chemical, physical, optical, mechanical and electronic properties of surfaces and supramolecular assemblies. He and his students have developed new techniques to expand the applicability and chemical specificity of scanning probe microscopies. They have applied these and other tools to the study of catalysis, self- and directed assembly, physical models of biological systems, and molecular and nano-scale electronics. They work to advance nanofabrication down to ever smaller scales and greater chemical specificity in order to connect, to operate, and to test molecular devices.