Many of the most exciting questions in biology can be addressed in new ways by exploiting the growing capabilities for experiments at the cellular, subcellular and molecular length scales. We envision a new form of biotechnology formed by the union of nanostructure fabrication and biotechnology. We are exploiting nanofabrication to perform individual molecule analyses in biological systems, to study cellular response to structured interfaces and to interrogate dynamic life processes at reduced dimensions. Our research has advanced the ability to structure materials and pattern surface chemistry at subcellular and molecular dimensions, and these continue to be fundamental technologies on which the research of the NBTC is based. It is our vision that nanobiotechnology will be the genesis of substantial new insights into how biological systems function, and conversely, nanobiotechnology will lead to the design of entirely new classes of micro- and nanofabricated devices and machines. These far reaching innovations cannot be carried out by single-investigators. The NBTC has established an organization to promote interaction and coordination of collaborative research efforts.

The research of the Center is organized in the form of interactive Research Programs that coordinate collaborative Research Projects with communications among the programs, facilitated by the Technology Platforms. The three technology platform leaders organize the NBTC seminar series, oversee the annual symposium, and facilitate inter-program technology utilization.

The four major research programs proposed for the next phase of the center have evolved from the original programs. These new research facilities are covered in detail the following pages. They have been derived from extensive internal and external review and our evaluation of the current challenges and opportunities in nanobiotechnology. These are dynamic and will continue to evolve over the life of the center. The collaborators participating on these research programs are not fixed but will continue to change as specific research projects are initiated.

In the first three years of existence, the NBTC has had a major impact on the national scientific and technological base. Examples of notable advances leading to future efforts include:

- Center research has resulted in new capabilities for single enzyme isolation and investigation. This effort is motivating a new class of experiments in single enzyme studies both in the NBTC and throughout the scientific community. Initial discoveries utilized for analysis of ATPase and DNA polymerase are being expanded to cellulase and other enzymes.

- Significant advances have been made in integrated bioanalytical systems enabled by advances in fluidic systems. These include new methods of fluid system fabrication and their integration with optical spectroscopy and mass spectroscopic analysis. This is being exploited for protein analysis and diagnostic device development.

- Studies of dynamics of cellular chemical communications were made possible by new integrated subcellular electrochemical probes, integrated with optical systems. These will be used for analysis of cellular activity in response to stimuli and for single cell studies of cell biology.

- Studies of cell surface receptor function are leading the way for a new class of experiments facilitated by advances in high spatial resolution surface biochemical patterning.

- Biosensor technology is being advanced in joint activity with the DARPA optical biosensors area and in collaborative efforts with national laboratories.