Amorphous silicon based large area detector for protein crystallography

Proteins are commonly found molecules in biological systems: our fingernails, hair, skin, blood, muscle, and eyes are all made of protein. Many diseases simply arise because a protein is not folded properly. Therefore, knowledge of protein structure is considered a prerequisite to understanding protein function and, by extension, a cornerstone for drug design and for the development of therapeutic agents. Protein crystallography is a tool that allows structural biologists to discern protein structures to the highest degree of detail possible in three dimensions. The recording of x-ray diffraction data from the protein crystal is a central part of protein crystallography. As such, an important challenge in protein crystallography research is to design x-ray detectors to accurately determine the structures of proteins. This research presents the design and evaluation of a solid-state large area at panel detector for protein crystallography based on an amorphous selenium (a-Se) x-ray sensitive photoconductor operating in avalanche mode integrated with an amorphous silicon (a-Si:H) charge storage and readout pixel. The advantages of the proposed detector over the existing imaging plate (IP) and charge coupled device (CCD) detectors are large area, high dynamic range coupled to single x-ray detection capability, fast readout, high spatial resolution, and inexpensive manufacturing process.;The design of an in-house a-Si:H TFT pixel array for integration with an avalanche a-Se layer is detailed. Results obtained using single pixel are promising and highlight the feasibility of a-Si:H pixels coupled with avalanche a-Se layer for protein crystallography application.;The requirement of high dynamic range is crucial for protein crystallography since both weak and strong diffraction spots need to be imaged. The main disadvantage of a-Si:H thin film transistor (TFT) array is its high electronic noise which prohibits quantum noise limited operation for the weak diffraction spots. To overcome the problem, the x-ray to charge conversion gain of a-Se is increased by using its internal avalanche multiplication gain. Since the detector can be made approximately the same size as the diffraction pattern, it eliminates the need for image demagnification. The readout time of the detector is usually within the ms range, so it is appropriate for crystallographic application. The optimal detector parameters (such as, detector size, pixel size, thickness of a-Se layer), and operating parameters (such as, electric field across the a-Se layer) are determined based on the requirements for protein crystallography. A complete model of detective quantum efficiency (DQE) of the detector is developed to predict and optimize the performance of the detector. The performance of the detector is evaluated in terms of readout time (<1 s), dynamic range (∼105), and sensitivity (∼1 x-ray photon), thus validating the detector's efficacy for protein crystallography.