This initiative will support projects that focus solely on development of technologies with the potential to enable acquisition of basic biomedical knowledge. Projects should be justified in terms of technical innovation, and utility for future biomedical impact.The products of this research will be functioning prototype instruments, methods, synthetic approaches, biological products, etc., characterized adequately to be ready for first application to the type of biomedical research questions that provide the rationale for their development, but application of the proposed technology to specific biomedical questions is considered beyond the scope of the program, should not be included, and would not be funded.Proof of principle for the technology will have already been shown, but there will still be significant fundamental technical challenges. Applications should include preliminary data. Projects that have significant remaining risk but are supported by early feasibility studies might be appropriate for a three year R01 proposal with reduced budget to better manage risk and investment. Projects that are well supported by feasibility studies and propose to develop fully functional prototypes might require higher budgets and a four year duration (five years for early stage investigators). Projects that primarily focus on optimization, hardening, or obvious extrapolations of established technology might be less competitive.