11

1. Watching DVDs in Real Time

Digital versatile discs (DVDs) are one of the mostconvenient ways of storing large amounts ofinformation. However, despite two decades ofdevelopment since the discovery of the materials onwhich they are based, details of how they work remainunclear. Researchers from RIKEN SPring-8 Center,JASRI, CREST and Matsushita Electric Industrialare filling the gaps in our understanding of thesematerials, using state-of-the-art time-resolved X-raydiffraction analysis to observe the change in theatomic level structure of these materials.

This is a report on the first successful outcome oftime-resolved pump and probe X-ray diffraction inSPring-8 by the pilot project “X-ray pinpoint structuralmeasurement ” organized by Japan Science andTechnology Agency (JST) as the Core Research forEvolutional Science and Technology (CREST) startedsince 2004 and to be completed by 2009. The X-raypinpoint structural measurement system is developedat the BL40XU high flux beamline (Fig. 1). The aim ofthe project is to achieve a picosecond time-resolvedX-ray diffraction experiment using a submicron-scalebeam. This is why the project is called “pinpoint.” Theaimed specifications of the X-ray pinpoint structuralmeasurement are ~100 nm spatial resolution and

~40 ps time resolution. Specialists in the fieldof accelerator science, laser physics, X-ray optics,diffraction physics, crystallography and chemistry arepart of this project (Fig. 2).

The research group has combined high-speedX-ray diffraction with in situ time-resolved laserreflectometry to simultaneously probe the structuraland optical properties of two different DVD materials,Ge

2Sb

2Te

5(GST) and Ag

3.5In

3.8Sb

75.0Te

17.7(AIST). This

has enabled them to track microscopic processes thatoccur in these materials, in real-time, as they changefrom an amorphous state to a crystalline state. Theyfound a gradual increase in both the reflectivity andemergence of diffraction peaks corresponding to thecrystalline phase, proving the close relationshipbetween the optical properties and structures ofthe materials. The differences in the widths of thediffraction peaks between the two materials and theirevolution over time led the researchers to propose twosubtly different models of the mechanisms takingplace in each. In GST, they suggested that largecrystal grains form over the entire volume of thematerial when the moment the process starts;however, in AIST, the process begins with theformation of small crystallites in different parts ofthe material, which gradually grow and merge to form

11

Endeavors at Frontiers of Research

A Place in the "X-ray" Sun

larger grains. The level of detail enabled by thisand future studies is l ikely to make a valuablecontribution to the development of better and fasterDVD materials.

The X-ray pinpoint structural measurementsystem is now close to completion in SPring-8. Thesystem, which is an integration of a time-resolvedexperiment and a sub-micron beam technique, will beapplied after its completion to the study of variousphenomena such as photo-induced phenomena, andstructural changes under applied AC electric field.

2. Capturing a Heartbeat Motion

Internal motions such as heartbeat, and thepulsation of blood vessels, are inherent in all livingcreatures. In a hospital, we are told to hold ourbreath when chest X-ray or CT images are taken toavoid motion blur. However, it is impossible to controlheartbeat. A research team composed of researchersfrom RIKEN, Kawasaki University of Medical Welfareand JASRI has designed and constructed a high-resolution, computed tomography (CT) system that

can sharply visualize the motion and deformationof the heart, coronary arteries and small airways oflive mice and rats, which are most often used asanimal models of human diseases.

Mice and rats have heart and respiration rateshigher than 300 and 100 per minute, respectively,making internal motions very fast. Since theseanimals are smaller than humans, the requiredspatial resolution is higher, making motion blur amore serious problem.

The RIKEN team solved this problem by controllingrespiration with a ventilator and monitoring heartbeatusing an electrocardiogram. Using a fast X-ray shutter,images were recorded only when the respiration andheartbeat were in their certain prescribed phases. Byrotating the animal in the X-ray beam and collectingimages, the team was able to accumulate data for the3D reconstruction of the chest. For more details onthis topic, see page 50 of this issue.

Figure 3 shows a comparison of thereconstructed cross sections of a mouse chest. Theresolution is 12 µm per pixel. The left image (A)is without synchronization, showing severe blurring.The center image (B) is with only respirationsynchronization, showing blurring of the heart. Theright image (C) is with respiratory and cardiac

Fig. 1. Schematic representation and photograph of X-ray pinpoint structural measurement system.

Curved imaging plate • Reflectivity monitor system • Laser wavelength 633 nm • Time-resolution 3 ns

.X-ray beam size 3 μm for 15 keV

.Incident X-ray intensity 104 photons/pulse for 15 keV.X-ray pulse duration 40 ps (FWHM)

Electron bunch RF cavity RF masteroscillator

Timing controlmodule

Femtosecondpulsed laser

Lens Photodetector

Disk rotation

Fresnel zone plate Laser for

reflectivity monitor Pulsed selector Channel-cut

monochromator

SPring-8 Storage ring

.Rep. rate 1 kHz

.Speed 50 mm/s

.Side-run out < 2 μm

.Data acquisition for a disk

Sample disk rotation system

1.8 M shots Acquisition time 30 min

• Timing precision ± 8.4 ps

• Laser beam spot size 30 μm• Laser pulse intensity < 500 μJ/pulse for 800 nm < 80 μJ/pulse for 400 nm• Laser pulse duration 100 fs (FWHM) Typ.

Lens

Undulator

Fig. 2. Members of X-ray pinpointstructural measurement project.

Fig. 3. Reconstructed cross-sections of mouse chestby high-resolution computed tomography (CT).

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synchronizations. The blurring is much reduced andthe bronchi and the heart are clearly visualized. Usingthis technique, they constructed sharp images of thelung after inspiration and expiration, and also thoseof the heart in systole and diastole.

This technique opens a way to high resolutionimaging studies of live animals. The high-resolutiondynamic structures of the lung and heart will help inour understanding of the function of these vital organs,especially by providing an experimental basis for thesimulation of gas exchange in small airways and ofshear stress in blood vessels using a supercomputer.

3. Coming Powerful Light

SPring-8 will soon start building a new beamlinefor inelastic X-ray scattering, i.e., the Quantum NanoDynamics Beamline BL43LXU, which has beenfunded by MEXT through RIKEN. The new beamlinewill provide unprecedented flux using a short-period,small-gap undulator installed in one of SPring-8's30-m straight sections. By operating in the fundamentalto maximize the ratio of flux to power load, such aflux will be the world's most brilliant X-ray source inthe 15 to 25 keV energy range, and provide thehighest flux, as shown in Fig. 4.

Associate chief scientist Alfred Baron has beenconsidering this project for more than 4 years andhas a numerous discussions with scientists aboutthe scientific goals for such a beamline - the membersof the workshop in 2008 are shown (Fig. 5). Thebeamline's scientific target, i.e., inelastic X-rayscattering with energy resolutions from < 1 to > 40meV covers some of the most challengingexperimental regimes today: the high-resolution(1 to 3 meV) setup is aimed primarily at atomicdynamics in crystals and disordered materials, andthe “medium-resolution” (6 to 40 meV) setup atnonresonant measurements of charge dynamics. This

is expected to provide a unique window on processesin many different types of material, and in differentpotential ly extreme condit ions. One area ofapplication, for example, will be in the new iron-arsenic superconductors discovered by Hosono'sgroup. With superconducting transition temperaturesthat are only exceeded by those of some copperoxides, this new class of high-temperaturesuperconductors shows a complex electronicstructure, magnetic order, and an extremely strongmagneto-elastic coupling. The twin windows ofmeV resolution for investigating atomic dynamics andof ~40 meV resolution for investigating electronicdynamics are expected to lead to new results - inaddition to the investigation of magneto-elasticinteraction, for example, direct investigation ofsuperconducting gap may be possible.

16 0

40

80

0

10

20

18 20 Energy (keV)

Bri

llian

ce

(1020

/s/m

rad

2 /mm

2 /0.1

% B

W)

Flu

x (1

014/s

/0.1

% B

W)

22 24

BL43LXU

BL19LXU

BL35XU

Brilliance Flux

Fig. 4. Comparison of the flux and brilliance availablefrom a standard insertion device (32 mm period by 4.5m long) at BL35XU and the one planned for BL43LXU(19.4 mm period, 17.6 m). The brilliance of BL19LXU(32 mm period, 25 m) is included for reference.

Fig. 5. Workshop for new beamline “Quantum Nano Dynamics Beamline.”

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4. Heading to Next Goal: Sunbeam Consortium

In the last decade, the Sunbeam Consortium(Industrial Consortium for Beamline Construction andApplications) has contributed to new technologydevelopments as the front runner in industrialutilization with the Industrial Consortium Beamline(BL16XU/B2). The Sunbeam Consortium is a privateorganization consisting of 13 companies (12 companiesand 1 electric group): Kawasaki Heavy Industries,Ltd., Kobe Steel, Ltd., Sumitomo Electric Industries,Ltd., Sony Corp., Electric power group (Kansai ElectricPower Co., Inc., Central Research Institute of ElectricPower Industry), Toshiba Corp., Toyota Central R&DLabs., Inc., Nichia Corp., NEC Corp., Hitachi, Ltd.,Fujitsu Laboratories Ltd., Panasonic Corp. andMitsubishi Electric Corp.

The SPring-8 research of the SunbeamConsortium has successfully been applied to thedevelopment and improvement of manufacturingprocesses for various types of product such asadvanced semiconductor devices, high-densitymagnetic disks, laser diodes, optical fibers, high-

corrosion-resistance steel, automotive catalysts andfuel batteries.

On the basis of the activities over the past 10 yearsand the next-term research plans, the SunbeamConsortium renewed their contract with JASRI, who isin charge of SPring-8 operation, for the continuousinstallation and operation of the Industrial ConsortiumBeamline for the next 10 years starting from August27th, 2008.

For the next term, a large-scale capital investmentof approximately 320 million yen was made to renewthe experimental equipment (Fig. 6). The mainupgrades achieved are as follows:

(i) X-ray diffractometer and scattering measurementsystemThe system increased the number of movable axes ofthe sample stage from 4 to 8. This improvement canprovide high measurement flexibility and reducemeasurement time to half. The new large samplestage allows the mounting of a large wafer up to300 mm diameter and the measurement of the entireproduct, instead of a test piece or a cut-out sample.

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BL16B2 16B2 experimental hutch

16XU optics hutch

16B2 optics hutch

Focusing mirror

Focusing mirror

Double-crystal monochromator

Radiation shield Radiation shield SR

SR

4-axis diffractometerwith an analyzer crystal

Gas flow system for in situ analysis

(modified for using at both beamlines)

X-ray microbeam instrument X-ray fluorescence spectrometer

Double-crystal monochromatorwith liquid N2 cooling system

6-axis diffractometerwith an analyzer crystal

Modification of experimental tablefor new detectors

New detectors .19 element Ge SSD (solid-state detector) .2D flat-panel detectorBL control instrumentsHutch modification

BL16XU 50

30 40

20

40 60 50

30 40

20

40 60

16XU experimental hutch 16XU experimental hutch

Fig. 6. Beamline diagram and photograph of the Industrial Consortium Beamline (a) BL16XUand (b) BL16B2. Upgraded parts of experimental equipment are indicated in red.

X-ray fluorescence spectrometer

6-axis diffractometerwith an analyzer crystal X-ray microbeam

instrument

(a)

4-axis diffractometerwith an analyzer crystal

Experimental table

19 element Ge SSD

(b)

Consequently, the structure and interface structuralanalysis of a 1-nm silicon oxide layer on a 300-mm-diameter wafer used in the production line has beenaccomplished; it is the world's highest precisionmeasurement. This achievement is also madepossible by significant progress in the dynamic rangeof measureable data up to 12 orders of X-ray intensitymagnitude from 10 orders of magnitude for the X-rayreflectivity measurement.(ii) X-ray fluorescence measurement systemThe element analysis is available even for ultra-dilutesamples. The element mapping area also increasedto be applicable to 200-mm-diameter wafers with10 µm resolution. Chemical state analysis is alsoavailable as well as composition analysis with XAFSmeasurement. High-performance equipment willprovide a solution to the various types of problemconcerning devices, and contribute to thedevelopment of novel sustainable materials andcommercial products such as hexavalent-chromium-free plating.(iii) Microbeam techniqueThe function of X-ray diffraction analysis is relatedto the focused beam whose diameter is less than300 nm. X-ray intensity increases over one order ofmagnitude at the sample position. This techniqueenables microstructure analysis, such as designing amicro-magnetic head for high capacity, analyzinghead materials, and improving the fabrication process.

Full operation was restarted from the second halfof the fiscal year 2008. The utilization of the newfacil i t ies and equipment wil l al low previouslyunattainable level of analyses and observations, suchas ultrathin-film and sub-micrometer analysis, real-time observation and direct observation of commercialproducts.

5. Finding a Way to Overcome Diseases

From the beginning of modern drug discovery, anynew drug is the result of complex efforts includesmany steps such as assays, clinical trials and amongothers. Even today, drug development takes years,and the costs for screening and safety testing are veryhigh and rising. Discovering drugs targeting infectiousdiseases has the added complication that a singlemutation of the target virus or microbes may renderthe drug ineffective. Therefore, rapid drug discoveryis even more important in this case; moreover, suchdrugs should target some essential biological processto limit survival of the pathogen.

Structure determination of drug-target proteinshas long been recognized to assist drug discovery,because knowledge of the protein structure helpsbuild drugs which fit into it and bind tightly. Recent

developments in structural biology, including theimprovement of synchrotron beamlines, have greatlyaccelerated the pace of protein structuredetermination, and enabled structural genomicsgroups to solve drug-target proteins very rapidly.Although the number of the results are not somuch more but several important drugs has beendeveloped.

For example, the influenza drugs zanamivir(Relenza) or oseltamivir (Tamiflu) target the viralneuraminidase, which is an essential protein forrelease of the virus from host cells. Unfortunately,influenza can develop resistance to these drugs, andnew ones are urgently required to treat such resistantstrains.

In 2008, Prof. Park and his group from YokohamaCity University have determined the structure of apiece of the influenza RNA polymerase. This family ofenzymes is essential to all biological species, beingrequired to utilize genetic information stored in DNA.However, the influenza enzyme is assembled fromthree polypeptide chains unique to the virus, anddisruption of its assembly blocks replication of thevirus inside host cells. Two subunits, called PA andPB1, bind together through part of their structureto form a complex, which is necessary for the RNApolymerase to function. The structure of this complexrevealed the interaction between subunits, andthis structure is being used to guide new drugdevelopment (Fig. 7). Detail in this topic can befound in Park et al.'s report in this issue on page 18.

15

(a) (b)

(c)

Fig. 7. Influenza RNA polymerase complex. (a) Schematicdiagram of PA, PB1 and PB2 subunits of the influenzaRNA polymerase. (b) Crystals of the complex. (c) An overallribbon diagram showing the fold of PA, with helices in red,strands in yellow and coil in green. Helices are numberedfrom the N terminus. PB1 residues are in dark blue.

Masaki Takata