The macromolecular machinery that supports cellular functioning principally operates on the scale of nanometers, and nanoscale science and technology are broadly recognized as important emerging disciplines, with broad potential to impact the development of new drugs and diagnostic devices. A principal challenge to realizing this potential is the difficulty of precise manipulation and modification of materials at the nanometer scale. This can be addressed by applying the recent discovery of femtosecond laser nanomachining and ablation. The precision of damage produced by femtosecond pulsed lasers is so great that it enables selective laser ablation and machining at scales far smaller than the limits that diffraction typically places on optical techniques. Here we propose to construct a device that will use this approach for targeted subcellular surgery, and machining devices for biomedical applications. This will address the rapidly growing demand for nanoscale research and processing methods, and will be applied to research in basic and applied biomedical science. Proposed applications include: investigations of fluidic and lab-on-a-chip devices;subcellular surgery and ablation for medical and biological research;nanopores for biological sensing and diagnostics;nanofabrication and protein patterning of substrates to control and study cellular adhesion and motility. Application of this instrumentation to an even broader range of biomedical studies involving additional investigators will be actively investigated and encouraged.