High throughput laboratory X-ray illumination system for protein crystallography and screening

Sigray, Inc., Concord CA

Investigators

Linked publications, trials & patents

Abstract

? DESCRIPTION (provided by applicant): High throughput laboratory x-ray illumination system for protein crystallography and screening. X-ray protein crystallography is the single most effective method to determine macromolecule structures such as proteins. The understanding of the three-dimensional structure of proteins gives key insight into their functionality and provides essential information for rational drug design, which uses information on the structure of an active site of a critical enzyme in a metabolic or regulatory pathway in order to rationally design chemical compounds to inhibit or activate the enzyme's function in order to treat human diseases. The structural information from this technique has led to the engineering of new proteins as well as clinical trials for cancer and Alzheimer's drug targets. We propose to develop an X-ray illumination system comprising a source using a novel 3D microstructured anode and a high performance ellipsoidal capillary optic with a large solid angle collection. The anode provides superior heat dissipation, by incorporating microstructures of an x-ray producing material embedded within diamond, which has outstanding thermal properties and low mass density. This illumination system will provide more than 10X higher x-ray flux and flux density at the macromolecular crystal in comparison to state-of-the-art rotating anode sources. Additionally, it enables production of high flux of X-ray spectral lines in a single x-ray source t use multi-wavelength anomalous diffraction (MAD) phase techniques that are currently not accessible in a laboratory system. The proposed phase I project is a proof-of-principle demonstration that such a microstructured anode can indeed be manufactured and to validate its thermal dissipation advantages. At least ten prototypes of the novel microstructured anode will be fabricated; using copper microstructures embedded in diamond for the Phase I prototypes. Furthermore, we will confirm and assess the thermal mechanical properties through finite element modeling and empirical measurement during thermal cycling of the prototypes.