The instrument we refer to as """"""""Big Bang"""""""" uses a moderately powered laser flash to initiate the release of photolabile """"""""caged"""""""" groups such as protons, which then will induce conformational changes in a biological polymer such as a protein or DNA. The conformational changes of the polymer will induce acoustic waves within the solution resulting from phenomena such as changes in partial specific volume, electrostriction or changes in solvation. A piezoelectric transducer will detect the acoustic pressure waves (i.e. """"""""listen"""""""" to the ultrasound generated), and deconvolution techniques will be used to analyze the kinetics of the resulting conformational change. Optical methods, including Rayleigh light scattering, will also be used to monitor conformational changes. With access to the nanosecond and microsecond time scales, this instrument will be orders of magnitude faster than traditional stopped flow techniques which typically have mixing times on the order of a millisecond. It should also be less expensive to build. We expect this instrument to find large markets in biotechnology research and industry, particularly in studies involving protein folding. We propose here to build a prototype of this instrument and test the feasibility of this approach for measuring helix- coil transitions in a model protein system, poly-L-glutamate.
