Nuclear Instruments and Methods in Physics Research A 477 (2002) 166–171

Large area high-resolution CCD-based X-ray detectorfor macromolecular crystallography

Maja Pokri!ca,*, Nigel M. Allinsonb, A.R. Jordenc, M.P. Coxc, A. Marshallc,P.G. Longd, K. Moond, P. Jerrame, P. Poole, C. Navef, G.E. Derbyshireg,

J.R. Helliwellh

aUMIST, Department of Electrical Engineering and Electronics, P.O. Box 88, Manchester, M60 1QD, UKbUMIST, UK

cOxford Instruments, UKdYork Electronics Centre Ltd., UK

eEEV Ltd., UKfCLRC Daresbury Laboratory, UK

gCLRC Rutherford Appleton Laboratory, UKhDepartment of Chemistry, University of Manchester, UK

Abstract

An X-ray detector system for macromolecular crystallography based on a large area charge-coupled device (CCD)sensor has been developed as part of a large research and development programme for advanced X-ray sensor

technology, funded by industry and the Particle Physics and Astronomy Research Council (PPARC) in the UK. Theprototype detector consists of two large area three-sides buttable charge-coupled devices (CCD 46-62 EEV), wherethe single CCD area is 55.3mm� 41.5mm. Overall detector imaging area is easily extendable to 85mm� 110mm. The

detector consists of an optically coupled X-ray sensitive phosphor, skewed fibre-optic studs and CCDs. Thecrystallographic measurement requirements at synchrotron sources are met through a high spatial resolution(2048� 1536 pixel array), high dynamic range (B105), a fast readout (B1 s), low noise (o10e�) and much reduced

parallax error. Additionally, the prototype detector system has been optimised by increasing its efficiency at low X-rayenergies for use at conventional lab sources. The system design of the prototype detector is discussed and the proposedmethod for crystallographic data processing is briefly outlined. r 2002 Elsevier Science B.V. All rights reserved.

PACS: 07.85.Qe; 07.85.F

Keywords: Large area CCD; Crystallography; Data processing; Detector optimisation

1. Introduction

The Innovative Microelectronic Pixellated sen-sors and Advanced CCD Technology (IMPACT)

programme has been established to improveexisting systems and develop advanced sensortechnologies for X-ray energy-resolving detectors(ERDs) and large area imaging detectors (LADs).This programme is funded by industry and theParticle Physics and Astronomy Research Council(PPARC) in the UK. Four different detectors havebeen pursued within this programme. Two projects

*Corresponding author.

E-mail addresses: maja@sound.ee.umist.ac.uk (M. Pokri!c),

allinson@umist.ac.uk (N.M. Allinson).

0168-9002/02/$ - see front matter r 2002 Elsevier Science B.V. All rights reserved.

PII: S 0 1 6 8 - 9 0 0 2 ( 0 1 ) 0 1 8 8 1 - 2

(ERD1 and ERD2) have been undertaken toproduce energy-resolving systems, based on silicontechnology, and aimed primarily at X-ray fluores-cence applications. The other two IMPACTprojects (LAD1 and LAD2) have been concernedwith the design and development of large areadetectors, particularly for the use in X-ray macro-molecular crystallography. This paper presentsdetails of the LAD2 project, aimed to extend thetechnology of existing CCD-based systems formacromolecular crystallography by addressing theparticular needs for efficient and accurate mea-surements at conventional laboratory and syn-chrotron sources, and applying advanced signalprocessing for crystallographic data.

2. Design and development of the detector system

LAD2 detector programme has been directed atthe design and development of a large area CCDsensor, as a step towards the production of ‘wafer’size silicon detectors. The detector system is shownin Fig. 1, with the main components indicated.

A key challenge of this project has been theproduction of large CCD devices, with acceptableperformance and good yield. The CCD Technol-ogy section of EEV Ltd has designed a large(55.3mm� 41.5mm) three-sides buttable CCDsensor (CCD46-62) with 2048� 1536 matrix ofsquare pixels. As the CCDs are three-sidesbuttable, they can be used to create effectivelycontiguous 2� 2 or greater mosaics. The proto-type detector module containing two CCDs andassociated electronics hardware can be easilyextended to 110� 83mm2 imaging area. Sensor

pixel size (27 mm� 27 mm) has been optimised forprotein crystallography with small crystal samplesand small SR source size. On-chip pixel binningtechnique can be used to effectively increase thepixel size and dynamic range. The thickness ofmedia used for optical coupling between CCD andfibre optics directly influences the PSF, hence theCCD die has to be as flat as possible to reducespatial non-uniformity of PSF. EEV has been ableto achieve the flatness of die to within a 10 mmbow. The detector system has been optimisedthrough the reduction of the system noise andincrease of its detection efficiency so that weakdiffraction spots at low X-ray energies can berecorded. The detector system noise has beenminimised through careful readout electronicsdesign and reduction in dark-current noise byusing an external cooling arrangement. For theoptimal measurements of both, strong and weakdiffraction spots, CCD incorporates the feature ofreal-time switchable gain of on-chip outputamplifiers, hence extending the detector’s linearity.In order to reduce readout time, up to four CCDoutput channels can be used in parallel incombination with 2MHz ADCs. Operating para-meters of the CCD46-62 are given in Table 1.

A two-stage Peltier cooler is used to maintainthe CCD at its operating temperature. Thehydrofluoroether (HFE-7100) cooling superfluidat –10oC is circulated through the heatsink of thePeltier cooler as it has low viscosity and good heattransfer characteristics.

Fibre-optic (FO) studs (1:1 demagnification)have been used in order to maximise the system’sdetective quantum efficiency (DQE) and minimiseoptical distortions. FO studs are soft-bonded toCCD using the technology developed by PhotonicScience, with an achievable gap of less than 10 mm[1]. FO studs are skewed (see Fig. 2) so that thespacing between the sensors is reduced to only100 mm, hence minimising the dead zone fordiffraction data collection. FO studs with EMAare used in order to minimise the light scattering(PSF). The thickness of the studs is 18mm, fibresize is 6 mm, NA is unity and core-to-clad ratio is75:25 in order to maximise the light transmission.

The phosphor screen made from Gd2O2S:Tb hasbeen optimised for this detector with respect to theFig. 1. LAD2 detector system (CAD).

M. Pokri !c et al. / Nuclear Instruments and Methods in Physics Research A 477 (2002) 166–171 167

required spatial resolution and system gain. Sincethe detector system uses FO studs the phosphorlight transmission is high, hence a reflectingcoating has not been used to increase the light

yield. The thickness of the phosphor screen ischosen to be 20 mm optimised for the energy rangeof 5–25 keV. A theoretical model of phosphor gain[2,3], for the range of thicknesses, substantiate the

Table 1

CCD and associated electronics operating parametersa

Two channel Four channel

Aperture (mm�mm) 55� 42

Pixel size (mm�mm) 27� 27

Array size 2048� 1536 (+25)

Total active pixels 3.20M

Pixels/channel 1.602M 0.824M

Estimated line transfer overhead (ms) 250

Pixel time for 1 s total readtime (ms) 750

Pixel dwell time (ms) 470 910

Pixel rate (MHz) 2.13 1.10

Total readtime–1MHz adc (s) 1.85 1.07

Total readtime–2MHz adc (s) 1.06 0.66

Data rate for 1MHz adc (MB) 3.40 5.90

Data rate for 2MHz adc (MB) 5.94 9.53

Data rate for 1 s total readtime (MB) 6.29

Full well capacity (� 106e–) 0.5

LSB equivalence for 16-bit adc (e–) 7.6

Dark current (e�/s pixel�1) (at 293K) 500

Dark current (e�/s pixel�1 ) (at 233K) 0.9 e�/s pixel�1

Readout noise (e�/pixel) (at 1MHz pixel rate) 5/15

Amplifier peak signal (e�/pixel) B106 (OG2 high); B1.5� 105 (OG2 low)

Amplifier responsivity (mV/e�) 1.5 (OG2 high); 4.5 (OG2 low);

QE B35% at 550nm

aNote: Line transfer overhead is estimated for IMO device. Readout rates, etc. include 16 pixel run-outs per channel. No on-chip

binning assumed.

Fig. 2. Skewed FO studs configuration.

M. Pokri !c et al. / Nuclear Instruments and Methods in Physics Research A 477 (2002) 166–171168

choice of the phosphor thickness (see Fig. 3). Areplaceable screen, provided by EEV, will be usedfor initial trials. Further trials of alternativescreens are planned and the option of a phosphordirectly deposited on the fibre optic is retained.

3. Detector performance

The detector system performance is specified interms of its main parameters such as system gain,DQE and PSF through the use of theoreticalmodels and in some instances experimental ver-ification (e.g., PSF determination). The systemgain is calculated using photon transmission andconversion processes through the detector systemchain, namely entrance window, sample-to-detec-tor media, phosphor screen, FO stud, opticalcoupling between CCD and FO and the CCDitself [2–7]. Fig. 3a shows calculated photontransmission through the entrance window, FOand normalised gain of the Gd2O2S:Tb phosphor.Fig. 3b illustrates estimated gain of the systemexpressed as the number of detected electrons perincident X-ray photon. The detector system isoptimised to operate at 12 keV, although it isefficient over the whole range of photon energiesused in macromolecular crystallography experi-ments.

Fig. 4 shows calculated DQE curves for anumber of X-ray energies (14, 18 and 25 keV) for

two different integration times (10 and 100 s) [8,9].It can be seen that the DQE is highest at 14 keV,which is the result of phosphor absorption anddetector gain choices.

The PSF was experimentally obtained fora prototype phosphor sample of 10mg/cm2

(B45 mm with a packing fraction of 30%)Gd2O2S:Tb coated with carbon-based absorbersupplied by Applied Scintillation Technologieswhich was directly coated onto a 2mm FO studand coupled to a test CCD (02-06 EEV) with 3mmthick FO face plate. The PSF (FWHM=45.5 mm;10% of max=94.5 mm and 1% of max=175.1 mm)

Fig. 3. (a) Main transmission curves of detector components across desired energy range, and (b) resulting detector system gain curve.

Fig. 4. DQE curves calculated for the LAD2 detector.

M. Pokri !c et al. / Nuclear Instruments and Methods in Physics Research A 477 (2002) 166–171 169

was obtained using a laboratory X-ray source witha Cu target (8 keV peak photon energy).

4. Crystallographic data processing

The main objective of the crystallographic dataprocessing is to accurately identify the positionsand integrated intensities of all Bragg peaks in theX-ray diffraction data. A conventional method isto fit a reference profile to the data in a shoeboxaround the position of each detected Bragg peakusing a least-mean-squares procedure, with theintensity of the reference peak as the onlyadjustable peak parameter [10–12]. However, asthe Bragg peaks can often be non-symmetrical(over the full detection aperture) or can overlap,this method can lead to gross errors in thedetermination of peak intensities. A more robustapproach is being investigated, based on radialbasis function (RBF) neural networksFa wellestablished technique that has been applied to awide variety of problems such as image processing[13], speech recognition [14], adaptive equalisation[15] and medical diagnosis [16]. Fig. 5a shows theRBF approximation of two closely positioneddiffraction spots. As it can be seen, the RBFnetwork successfully isolates two overlappingpeaks simultaneously, which eliminates the need

for the shoe box approach in crystallographic dataapproximation. The deconvolution of overlappingpeaks can be achieved by separating two or moresets of neurons (RBF centres marked as crosses inFig. 5b) contributing to each of the peak. TheRBF network approximation of Bragg peaks isobtained in analytical form (i.e., sum of Gaussianbasis functions), hence the integrated peak inten-sities are straightforward to calculate once thebackground has been estimated.

5. Conclusions

Though there is considerable investment in thedevelopment of solid-state pixel detectors (whichwill potentially provide faster readout and im-proved performance for very low intensity diffrac-tion spots), it is unlikely that such systems will bereadily available, in a fully characterised state, forseveral years especially with pixel linear dimen-sions less than 50 mm. Hence, for standard datacollection from physically small samples and verylarge molecules (e.g., viruses), there will be acontinuing need for very high resolution detectorsystems based on large-scale CCDs. The systemdescribed in this paper forms the prototype for thisimportant line of instruments in the ever expand-ing drive to determine the structures of the many

Fig. 5. (a) RBF approximations of two neighbouring Bragg peaks with indicated individual pixel intensities (marked as circles), and

(b) contour plot of RBF approximation with indicated positions of RBF centres (marked as crosses).

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thousands of macromolecules that form thebuilding blocks of life itself.

Acknowledgements

This work, as part of the IMPACT programme,is supported by UK industry (notably OxfordInstruments, EEV and BNFL) and grants, viaPPARC, from the UK Foresight Initiative Chal-lenge. University partners within IMPACT areUMIST, Imperial College of Science and Technol-ogy, and the Universities of Leicester and Glas-gow; together with the UK’s Central Laboratoriesof the Research Councils (Rutherford–AppletonLaboratory and Daresbury Laboratory). All thisassistance and generous access to national facilitiesare gratefully acknowledged.

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