SBIR-STTR Award

Determination of detailed atomic structures of proteins and DNA has offered a wealth of information on the working of biological systems. Macromolecular crystallography has provided the vast majority of information on the structures of viruses, proteins (including those of medical significance), and nucleic acids. Yet, the act of crystallizing a macromolecule remains a trial-and-error process which often requires long periods of time and a large supply of sample. Our goal, as described in the Phase l SBIR proposal, is to design and test a prototype protein crystal reaction chamber which will offer a new method to crystallize macromolecules. In our device, a "voltage permeated" membrane will keep protein and precipitant solutions separate until an electric field is applied to the system. At that time, precipitant buffer will enter the protein chamber and initiate crystallization. Some of the features of our system include electrophoretic concentration of protein sample; monitoring and control of pH, temperature, mixing rates, and precipitant concentration during the experiment; rapid transition from nucleation to growth conditions; re-use of protein sample; ease of use; reproducibility. Our new device is expected to allow a better understanding of macromolecular crystallization processes as well as to provide a more rapid and rational approach to the crystallization of macromolecules. PROPOSED COMMERCIAL APPLICATIONS: Commercial applications are mostly in the field of protein crystallography itself. We anticipate selling units to schools, academic research groups, laboratories of pharmaceutical companies and other industrial laboratories worldwide when our technology proves to be superior to those currently in use. Supporting materials such as membranes, reagent solutions, control and monitoring units would also be sold. Additional applications of our methodology may be in other areas of biology (and in microgravity studies) in which solutions must initially be kept separate and later mixed in a controlled fashion (e.g. tissue culture, cell growth).

Determination of detailed atomic structures of proteins and DNA has offered a wealth of Information on the working of biological systems. Macromolecular crystallography has provided the vast majority of Information on the structures of viruses, proteins (including those of medical significance), and nucleic acids. Yet, the act of crystallizing a macromolecule remains a trial-and-error process that often requires long periods of time and a large supply of sample. Our goal, as described in the Phase I SBIR proposal, is to design and test a prototype protein crystal reaction chamber that will offer a new method to crystallize macromolecules. In our device, protein and precipitant solutions are kept separate until an electric field is applied to the system. At that time, a precipitant buffer will enter the protein chamber and initiate crystallization. Some of the features of our system include electrophoretic concentration of protein sample; monitoring and control of pH, temperature, mixing rates, and precipitant concentration during the experiment; rapid transition from nucleation to growth conditions; reuse of protein sample; ease of use; reproducibility. Our new device is expected to allow a better understanding of macromolecular crystallization processes as well as to provide a more rapid and rational approach to the crystallization of macromolecules.Proposed commercial application:Commercial applications are mostly in the field of protein crystallography itself. We anticipate selling units to schools, academic research groups, R&D laboratories of pharmaceutical companies, and other industrial laboratories worldwide when our technology proves to be superior to those currently in use. Supporting materials such as membranes, reagent solutions, and control and monitoring units would also be sold. Additional applications of our methodology may be in other areas of biology (and in microgravity studies) in which solutions must initially be kept separate and later mixed in a controlled fashion (e.g. tissue culture, cell growth).Thesaurus termsX ray crystallography, biomedical equipment development, crystallization, electrophoresis, macromolecule method development, nonclinical biomedical equipment, protein structure, structural biologyNational Institute of General Medical Sciences (NIGMS)