CAREER: Towards Fast, Multi-Parametric, Low-Radiation X-Ray Microscopy

University Of Houston, Houston TX

Investigators

Abstract

Using a multi-disciplinary approach, this proposal aims to develop novel theoretical techniques and the apply them to develop instrumentation and signal processing algorithms to enable the practical use of tomographic x-ray microscopes on biological samples. There is a significant need for nondestructive and quantitative microscopy in many biological investigations that this proposal addresses; that is, that sample preparation does not alter or deform the sample, that the details can be seen clearly and images captured with high resolution, and that the imaging process itself does not destroy the sample. Optical microscopes suffer from poor light penetration and low image resolution so sample preparation often requires slicing, fixing, staining and tagging methods that damage the samples. On the other hand, X-rays penetrate deeper in biomaterials and can image live, whole specimens nondestructively as is seen in medical applications. X-rays also have the advantage that there is minimal diffusion and scattering in biosamples, which can result in very high image resolution. However, current forms of absorption x-ray microscopy have poor contrast, low resolution and deliver high radiation doses to specimens. The proposed new generation of tomographic x-ray microscopes will provide quantitatively accurate, multi-parametric and high-resolution imaging data at low radiation dose; a first-generation prototype for a multimodality microscope will be tested during the project period. Engaging K-12 and undergraduate students in this type of interdisciplinary research will first require giving them the basic skills and knowledge for tackling problems that cross between physics, mathematics, engineering and biology. Students will be recruited from disadvantaged Houston-area school districts, and to retain their interest in STEM subjects a peer-mentoring program will be started, with special support provided for under-prepared segments of undergraduate students. To further motivate students to stick with STEM subjects organized summer camps will highlight interdisciplinary career opportunities and create research opportunities for undergraduates and high-school students. X-rays are of significantly higher frequency than visible light and thus offer the possibility of very high resolution and nondestructive microscopy. This project will develop methods to fully realize the potential of x-ray microscopes for bioscience applications. The project involves developing x-ray phase-contrast imaging using novel technology such as fast-pulsing x-ray tubes, photon-counting spectral detection schemes and algorithms to utilize the maximum information from each detected x-ray photons. The scientific goals of this proposal include theoretical methods, the design of a dose-efficient x-ray phase-contrast microscopy system on the basis of Monte Carlo simulations, construction of the system, and the development of an additional multimodality microscope prototype. A range of biological problems will be investigated to test the benefits of the imaging system. The developed methods will be broadly disseminated and the initial prototypes will be made available to researchers working on an array of biological applications.