The objective of this proposal is to develop a liquid calorimeter for protein analysis and designed to have volumes one-thousand times smaller and scanning rates up to one-thousand times faster than conventional instruments. This proposal applies the technology which has been so successful for making computer chips for the purpose of creating a new liquid Nanocalorimeter instruments for biological research. Understanding the underlying basic properties of proteins is fundamental to understanding their function. The high rates of the liquid Nanocalorimeter will allow researchers to observe the fast intermediate steps of protein folding. The design of this device will also enable the development of 100's of these devices on a single wafer of silicon. This Lab on a Chip configuration, which is ideal for automation, is a necessity for combinatorial studies. The extremely small sample sizes are also much needed for characterization for the synthesis of new proteins which are usually made at limited quantities. This research will provide a broad education for graduates students giving them practical hands-on experience in designing and fabricating devices of the future. The project also has broad technical impact in broadening the instrumentation for chemists and biologists. Advances in protein research directly impact the nation's health and medical industry, the most expanding segment of the economy. This research is important because it helps provide the infrastructure for protein discoveries. Synthesizing new types of protein is critical for advances in medicine and characterizing these new proteins is the first step in realizing their potential.