We have used simple nanofabricated structures to isolate individual biomolecules in solution in order to observe there activity and identity. We have employed metallic apertures a few tens of nanometers in diameter to confine a region of optical excitation to a volume on the order of 10@super -20@ liters, which allows the observation of single molecule motion and binding activity at meaningful rates and concentrations. This approach also enables detection of motility and binding of individual molecules in lipid layers and cell membranes. Small fluid channels have also been used to isolate individual optically detected molecules for evaluation in flowing systems. The mobility, molecular size and detection of discrete molecular binding events can all be done at the individual molecule level in such fluid systems. Nanofluidic devices with engineered dimensions, smaller than a relevant molecular length scale, can also be used to sort or control the confirmation of long biopolymers such as DNA. The engineered structures have the potential for integration into analytical systems that could exploit these single molecule analytical approaches.