Optical and electrical sensing has enabled the study of individual molecules in the gas or liquid phase, leading to an understanding of physical, chemical and biological processes on a very fundamental level. An integrated sensor platform is proposed that provides single-molecule resolution, extremely small gas or liquid sample volumes, planar architecture, and high throughput in a sensor array configuration. Such a sensor is highly desirable for providing fast, reliable and robust analytical tools. Without the need for bulky three-dimensional setup, these sensors can also be used outside a laboratory and could impact a variety of fields ranging from genomics and proteomics to toxicology and pollution monitoring in both air and water. Intellectual merit: The proposed approach is based on combining nanopore technology with single-molecule electrical resolution and antiresonant reflecting optical (ARROW) waveguides with liquid cores. The research has the following primary goals: 1. To build a new type of integrated optical sensor that simultaneously provides single-molecule fluorescence sensitivity and allows for parallel sensor array architectures. 2. To integrate nanopores as "smart gates" with the optical waveguides. The nanopores will control molecule access in the optical detection channel and simultaneously provide electrical sensing capability with single molecule resolution. 3. To use the novel combination of optical and electrical sensing to study biomolecules in genomics and proteomics for enhancing understanding of molecular biology on the single molecule level. While the concept is, in principle, equally applicable to sensing of molecules in the gas phase, the focus of this proposal is on integrated sensors of liquids for biomolecular studies on the single molecule level. Broader Impact: The research program outlined above has significant broader impact. It will advance optical sensor science and technology and provide graduate student training in the fields of integrated optics, molecular biology, and semiconductor device fabrication. Undergraduate research will be integrated into the program. At UCSC, students will participate in the project under the existing UC LEADS (underrepresented minorities) or COSMOS (K-12 students) programs. At BYU, undergraduates as well as high school students from underrepresented groups (BYU SOAR program) will be involved in the fabrication aspects of the projects during the summer.