Project Summary GM/CA @ APS operates a national user facility for macromolecular crystallography at the Advanced Photon Source. The two GM/CA undulator beamlines are world leaders in micro-crystallography due to a series of technical breakthroughs accomplished during the dozen years of GM/CA's development and operations. A unique operational feature of the micro-crystallography capability is the seamless integration of mini-beams with the large beam, enabling users to interchange the full beam (up to ~25x70 mm) with any of three mini-beams (5- mm, 10-mm and 20-mm diameter), and to do so rapidly (<3 sec), reliably and on demand for every sample as frequently as desired without need for beam realignment. The hardware for micro-crystallography is coupled with sophisticated software tools in the JBluIce user interface. A key tool is a raster feature to find micro-crystals in complex mounts or to identify the best diffracting regions of larger inhomogeneous samples. As a consequence of these developments, the GM/CA beamlines are oversubscribed due to the high demand by a growing number of investigators with challenging NIH-funded structural projects. Many have used the micro- crystallography capability to measure high-quality diffraction data from the most demanding types of samples, ultimately resulting in solved structures for systems of great biomedical significance. The beamlines have outgrown their current CCD-based detectors, which are inadequate for modern micro- crystallography practice, where far more samples are screened than data sets are collected and extensive rastering on individual samples is common practice. The previous generation of detectors does not have the speed and sensitivity to accurately measure weak reflections at the limits of the diffraction patterns, resulting in the unacceptable loss of the crucial high-resolution data. This application is a request for replacement of an outdated CCD-based detector with a high-speed, high- dynamic-range pixel-array detector (PAD) that is suited to the powerful micro-crystallography capabilities of the GM/CA beamlines and that will meet the needs of the NIH-funded investigators who make up the great majority of the GM/CA user base. PADs have been installed at several synchrotron sources worldwide where they are revolutionizing macromolecule data collection. The Pilatus3 6M PAD has a read-out rate 300-fold greater than the CCD-based detectors and a 23-fold greater dynamic range. The low read-out noise of the PAD and photon-counting read-out mode will result in a vastly improved signal-to-noise ratio to facilitate the collection of higher resolution data from challenging biological crystals.