X-Rays and Society

Since their discovery in 1895 x-rays have been the single most powerful technique for determining the structure of all forms of matter.  Through increasingly powerful imaging, diffraction, and spectroscopic techniques, physicists, chemists, biologists, and medical doctors, as well as quality-control inspectors, airline passenger screeners, and forensic scientists have resolved the structural detail and elemental constituency on length scales from inter-atomic spacing to the size of the human body.  Every day, that knowledge underpins our modern technologies, our health, and our safety. Quite remarkably, for the first 70 of these 119 years, x-ray sources changed little from the original Roentgen tube.  Even today, the x-ray technology used in universities, industrial labs and hospitals derives from this primitive electron tube with incremental improvements. 

Today, however, the benchmark for x-ray performance is set by large accelerator-based synchrotron radiation facilities costing more than $1 billion each and producing x-rays a billion times brighter than traditional small x-ray sources.  While small sources have a rich history of accomplishment (including about three-quarters of Nobel Prizes awarded for x-ray-based discoveries) since the late 20th century their performance has been eclipsed by the large facilities.  The large facilities are an artifact of 20th century science, using giant accelerators whose purpose was originally high energy physics.  Our aim is to create a new paradigm, where small sources have cutting edge performance and also have their traditional advantages of wide availability, ease of use in hospital or industrial settings, and their capability to test new ideas without the barriers of schedule, travel, and expense of the major facilities.

The Compact X-ray Light Source (CXLS) is a disruptive development that exploits recent advances in accelerator and laser technologies to create a vastly more powerful compact source rivalling the performance of the major facilities at a small fraction of their size and cost.  It will give scientists and medical researchers throughout academia, industry and medicine access to brilliant x-rays in their own laboratories, accelerating and broadening scientific discovery.
 


CXLS X-ray Science

Below we list a few major impacts that the CXLS can have.  However history shows that its biggest impacts are likely unknown today, instead awaiting discovery after it is built.  These topics include contributions from many authors including Kirk Clark (Novartis), Rajiv Gupta (Massachusetts General Hospital/Harvard), Wayne Hendrickson (Columbia University), Benjamin Hsiao (Stonybrook University), R. Joseph Kline (NIST), Alfons M. Molenbroek (Topsoe), David Moncton (MIT), Franz Pfeiffer (Technische Universität München), Theis Ivan Solling (Maersk Oil), Michael Toney (Stanford University), and Philippe Walter (Louvre Museum).

Cancerous human liver cells.  Left shows conventional x-ray image unable to distinguish cancer cells. Right image shows phase contrast image with cancer cells on left clearly visible.  This image is from a synchrotron; CXLS will enable such imaging in hospitals.  Courtesy of F. Pfeiffer, TU-Munich.

 

Phase contrast imaging. Clinical x-ray imaging systems including both plain radiography and computed tomography (CT) use x-ray attenuation to measure tissue contrast, producing the familiar medical x-ray image.  This traditional imaging cannot detect the small differences in density between neighboring soft tissues such as arterial plaque, or distinguish cancer cells from healthy tissue, or diagnose the increasingly common soft tissue wounds that our soldiers suffer from improvised explosive devices.  

X-ray phase-contrast imaging (PCI) uses subtle phase shifts of the x-ray electromagnetic waves instead of attenuation.  These phase shifts are a factor of 1000 more sensitive than attenuation and hold great promise to produce detailed soft-tissue images (figure above) and significantly reduce the x-ray dose to the patient.  PCI imaging can allow early diagnosis of breast cancer or image guidance in radiation therapy using unprecedented resolution in 3D.  It can image the cartilage, muscle and blood vessel damage in wounded soldiers.  Similar achievements have been obtained in imaging full human knees: high resolution simultaneous visualization of bone, cartilage and soft tissue was achieved with a single image. This is presently impossible with conventional clinical CT.

Macromolecular crystallography. The use of x-ray crystallography to determine atomic structures is nearly as old as x-ray diffraction itself.  Today macromolecular crystallography has become a mainstay of modern biology. Holdings of the Protein Data Bank are over 100,000 atomic structures, and growing at a rate of 10,000 per year.  Recent triumphs include the proton-driven ATP-synthase system for energy production, potassium ion channels to support nerve conduction, RNA polymerase to transcribe genes into RNA messages, ribosomes to translate the genetic messages into protein chains, and HIV envelope glycoproteins responsible for viral avoidance of immunity while infecting cells to cause AIDS.  Among these, four have been cited in the last ten Nobel Prizes in Chemistry.

Target-based drug discovery.  Healthcare is undergoing unprecedented change with an aging population and unhealthy lifestyles coupled with an ever increasing understanding of diseases.  Despite a healthcare need for rapidly introducing new medicines, drug discovery is a time consuming process that often takes more than a decade.  Early drug discovery can be enabled with an understanding of the fundamental disregulations in cells and pathways that lead to a disease state. 

The discovery, optimization and characterization of potential drug molecules involve generation and integration information from many technologies.  Single crystal, x-ray diffraction studies enable atomic resolution visualization of the target molecule engaging with the drug candidate.   Imatinib, which was one of the first examples of targeted therapy in oncology, employed protein crystallography in its development.

Radiation therapy.  In medicine, synchrotron radiation x-rays are used to develop new imaging, radiation therapy and surgery techniques, using in-vitro and in-vivo models. The aim is multifold, including developing basic knowledge, understanding living mechanisms, studying the physiological changes related to a disease, understanding the metabolism of some specific drugs, or even developing new diagnostic and therapeutical tools that can reach the general public through clinical implementation. In the latter cases, any development has to be oriented to dissemination outside large scale facilities, because large synchrotrons are too few and expensive to become an effective diagnostic and/or therapeutic instrument. Therefore the implementation of such techniques with a CXLS will be essential.

Microbeam Radiation Therapy (MRT) presently uses highly collimated, quasi-parallel arrays of 50-300 keV x-ray microbeams with widths from 50 to 500 microns, produced by large synchrotron radiation sources. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardio-synchronous movement of the tissues. Microbeams show an unprecedented sparing of normal radiosensitive tissues as well as preferential damage to malignant tumor tissues. Very high peak entrance doses are surprisingly well tolerated by normal tissues.

Potential medical application of this technique has been identified in the treatment of presently not curable brain tumors in children, in the treatment of lung cancer with low secondary effects, and in the highly precise radiosurgery application to treat pharmaco-resistant epilepsy.

Cultural heritage studies.  Research on cultural heritage materials such as paintings, sculpture, and other objects sheds new light on ancient technologies and helps in their preservation. The aim of this research is to identify the materials from a chemical and structural point of view (minerals, organic molecules, hybrid materials or condensed matters). Sometimes, it is the understanding of a diffusion mechanism, the observation of a patina on metals or the nature of nanocrystallized inclusions.  We also aim to understand the processes used for their elaboration (origin of the materials, recipes of chemical synthesis, metallurgy, mechanical treatments and thermal annealing, etc.), and describe the alteration and the aging behavior, including the issues concerning the preventive conservation and the restoration.

The use of a high-flux monochromatic x-ray source can provide a unique opportunity to have at one’s disposal methods for non-invasive elementary and structural analysis. The high resolution enabled by the CXLS is particularly well suited for the non-invasive study of ancient materials that often represent complex and heterogeneous samples. Hard x-rays offer the opportunity to analyze heavy elements with high accuracy, to explore their environment by absorption spectrometry and to better understand the material organization by x-ray diffraction or small angle x-ray scattering. By combining these measurements on one artifact, it is possible to assume that a total analysis of the materials will be worked out. This will remove all the ambiguity in the interpretation of their nature and aging, in all the possible cases, independent of the crystalline or amorphous nature of the sample, from metals to natural compounds.

Time-resolved chemistry and biology.  The knowledge of structure and dynamics of matter, on length scales from cm to nm and time scales from seconds to femtoseconds, is key for solving the great challenges that confront our societies. In chemistry, bio-chemistry and biology there is great interest in time-resolved spectroscopic investigations of the electronic structure of molecules in solvated systems, and in studying solvation dynamics with picosecond time resolution. Because the intensity of the individual pulses is such that the sample is not modified by the probing x-rays, the important parameter is the integrated number of incident photons which can be accumulated at the CXLS in a reasonable time.

Advanced water purification membranes.  Water desalination and water waste treatment are two of the most important global challenges of the 21st century.  Development of new membrane technologies, including the use of aligned carbon nanotubes, bio-based water channels, and nano-composite barrier layers with interfacial water channels, suggest promising new possibilities for low-energy desalination to replace high-energy consuming evaporative processes.

In the present context, advances in electro-spinning and fundamental synchrotron x-ray scattering studies on nascent cellulose crystals have provided the insight needed to use the fibrous format with varying pore sizes for applications from micro-filtration via ultra-filtration to nano-filtration and reverse osmosis.

The composite mats forming the membrane contain fibers with diameters ranging from sub-nanometer up to several micrometers and the membrane performance is closely related to dimensions of the fibers and their size distribution.  Small angle x-ray scattering (SAXS) and electron microscopy (TEM) are the indispensable and complementary methods to obtain this information.  The CXLS is particularly well suited to SAXS because it has a small source size, which can be transformed by x-ray optics to a small angular divergence, and an x-ray beam intensity comparable to that available at large facility SAXS instruments, due to its few percent bandwidth.

Photovoltaic and energy storage materials.  Perhaps the most significant developments in the use of x-rays in research on materials for sustainable energy are measurement methodologies conducted in-situ and operando. These techniques enable researchers to actually watch how functional materials form (synthesis) and operate (function), including degradation.  The methods are also generically applicable to a huge variety of materials, including batteries, catalysts, photovoltaics, and efficiency materials (e.g, smart windows).

With regard to photovoltaics, x-ray based techniques have been ubiquitously used to characterize the complex absorber and transparent conductor materials that make up these solar cells as well as the processing of these. Thin film and ‘emerging’ solar cells are possible replacements for the presently used Si cells and offer the potential for lower cost and energy intensity for manufacturing. Organic photovoltaics (OPV) are another possible emerging PV technology that may be extremely cheap, due to newspaper like printing of the cells, and can be deployed on flexible substrates, enabling presently unimaginable applications.  

Semiconductor fabrication metrology. The critical dimensions of features lithographically etched on electronic chips continue to shrink in size, today reaching about 30 nm, with continued rapid progress expected.  However the traditional method of measuring these features relies on optical scatterometry that is now mature and cannot be extended to smaller structures. Industry is thus unable to rapidly characterize their latest masks resulting in low yield and difficulties with the fabrication process.  A new x-ray diffraction technique, critical dimension small angle x-ray scattering (CDSAXS), developed at major synchrotrons has shown that it can accurately measure the smallest dimensions.  In fact, diffraction based techniques are even more effective as the feature size decreases so that all future electronic features can be accurately measured.  X-rays are sensitive to variations in composition and are capable of detecting buried features or determining the thickness of individual layers within a multilayer structure. They are also sensitive to the average level of roughness, which must be carefully monitored to ensure the reliability of the final product. All of these features make the development of in-lab or in-line metrology attractive to the semiconductor industry. The CXLS presents a major breakthrough because it allows application of CDSAXS directly in the semiconductor fab plant.

Mineral morphology for enhanced oil and gas extraction. It is a general challenge to extract a larger fraction of crude oil than is presently possible from complex off-shore carbonate reservoirs.  In this context it is of utmost importance to characterize by computed x-ray tomography the connectivity and size distribution in three dimensions of the pore-space in the oil-containing rock with a spatial resolution ranging from tens of nanometers to tens of micrometers.  Also the surface structure and the chemical composition of the pore-surface are of great importance, and again x-ray tomography is an invaluable tool together with more fundamental studies of prepared model surfaces using x-ray reflectivity and diffraction.

Conventional CT scanning instruments are limited to a spatial resolution of order one micrometer, and the data acquisition time for just one sample is typically 16 hours.  A spatial resolution of order 200 nm could be achieved with the CXLS and permit CT scans in a minute, enabling time-resolved flow studies both on real samples from the oil-containing rock as well as from suitable phantom samples, so that model simulations of flow can be compared with reality.