BIOMOLECULE CRYSTALLIZATION MICROARRAY

The proposed innovation is a microelectromechanical system (MEMS) for automated, kinetically controlled growth of biomolecule crystals for crystallography. Central to the innovation are two novel components: a peristaltic micropump that delivers nL/s flows and a flow sensor that measures such flows. Pumps and sensors will allow delivery of buffer, precipitant, and biomolecule solutions to an array of 10-muL microreactors at individually controlled flow rats. The three pumps serving each microreactor will be coordinated to maintain optimized nucleation conditions and separately optimized crystal growth conditions. Active control requires monitoring of nucleating/growing crystals, so a Phase I survey of optical and electronic methods will identify aan appropriate monitoring technology for Phase II implementation. A stand-alone Phase microreactor, served by precision laboratory syringe pumps, will be tested by growing hen egg-white lysozyme crystals under controlled optimized conditions. Thus, Phase I has three Specific Aims: (1) microfabrication and testing of the micropump and flow sensor, (2) selection of a crystallization monitoring method, and (3) fabrication and testing of a stand-alone feed-controlled crystallization microreactor. In Phase II, the elements will be assembled into a prototype crystallizer, and then an array of simultaneously operable reactors will be built for beta testing.