Pépinière de Luminy avenue de Luminy - case Marseille – 1 New detectors for X-ray imaging

Pépinière de Luminy avenue de Luminy - case Marseille – 2 What makes the XPAD hybrid pixel detector better than CCDs & CMOS Signal to noise Frame rate (images/s) ratio quality at low dose rate Ultra fast High diagnostic power New imaging area Shooting of ultra fast phenomena Time resolved imaging > 500

Pépinière de Luminy avenue de Luminy - case Marseille – 3 The markets For the first two years, we aim to produce X-ray detectors for applications where we are already well known, namely fundamental and applied research (material and protein crystallography, monochromatic CT, …) and small animal imaging. Together with the CPPM, we will pursue R&D on the development of a large CdTe detector in order to enter the huge market of color imaging. SHORT TIME MARKETS FUTURE MARKETS Clinical imaging Waste sorting Homeland security Non-destructive control Dental imaging

Pépinière de Luminy avenue de Luminy - case Marseille – 4 Reciprocal space tomography using the XPAD detector at SOLEIL (courtesy: M. Gailhanou, CNRS/IM2NP) imXPAD objectives The company is created for the industrialization and commercialization of XPAD detectors of different sizes and dimensions. The first detectors will be of small and medium sizes, with the intent to increasing their dimension in a short time scale. For an efficient launch, the company will benefit from the collaboration of experts and equipments from CPPM. At start, the target market is the research on material sciences (synchrotrons and laboratories), either directly or via OEM. The market will then be soon extended to small animal imaging. Later on, other domains such as dental imaging, clinical angiography, clinical imaging, material survey and homeland security will be exploited. At the same time, imXPAD will collaborate with CPPM experts on R&D, in particular by developing large CdTe detectors to set up and demonstrate color CT imaging, a new way of imaging X-rays that will bring CT into the world of molecular imaging. imXPAD stands for “Imaging with the XPAD detector”. The XPAD detector (X-ray Pixel detector with Adaptable Dynamic range) is a hybrid pixel detector developed at the “Centre de Physique des Particules de Marseille” (CPPM, Université de la Mediterranee and CNRS/IN2P3).

Pépinière de Luminy avenue de Luminy - case Marseille – 5 imXPAD management team Bernard DINKESPILER, President of imXPAD, is an electronics engineer who worked for more than 25 years at CNRS-IN2P3, in the field of high energy physics experiments. After leading the department of electronics of CPPM (20 people), he joined the hybrid pixel development team in He is the author of the patents on the readout architecture of the XPAD3 chip. He has spent a few years at SMU (Southern Methodist University, Dallas- Texas, USA) as a senior research associate. Dr Pierre DELPIERRE, General Director of imXPAD, he is a scientist very well known in the international instrumentation community. He was at the origin of the hybrid pixel technology together with E. Heijne at CERN (Geneva, Switzerland). He was the project leader of the pixel detectors of the DELPHI (world premiere) and ATLAS experiments at CERN. The company will benefit of his scientific and technical experience, in particular for the research and development program. He is co-author of a patent that describes the use of photon counting for color CT. He was awarded the Crystal Prize of CNRS in 1997 and the Grand Prix of the French Academy of Sciences in Christian MOREL, Scientific advisor, is a physics engineer. He is professor at the Department of Physics of the Aix-Marseille University and chairs the imXgam – X and gamma ray imaging group at CPPM. He will share his experience in the field of biomedical imaging by attending the Administration Council of the society. He is co-author of a patent that describes the use of photon counting for color CT. He was laureate of the ANR Programme « Chaires d’excellence » in 2005 and received the Rotblat Medal in He has been elected member of the IEEE NMISC from 2005 to 2008 and is member of the the French GDR MI2B (Modelling and Instrumentation for Bio-Medical Imaging) council since 2008.

Pépinière de Luminy avenue de Luminy - case Marseille – 6 The imXPAD team imXPAD Management Board Bernard DinkespilerPresident Pierre DelpierreGeneral Director Christian Morel Scientific Advisor imXPAD operations and R&D Technical division (3 persons) Commercial division (1 person)

Pépinière de Luminy avenue de Luminy - case Marseille – 7 Our partners Technology transfer Tests on mice XPAD tuning in synchrotron beam R&D for color CT XPAD tuning in synchrotron beam

Pépinière de Luminy avenue de Luminy - case Marseille – 8 XPAD technology The XPAD detectors use the hybrid pixel technology developed for high energy physics. The idea is to provide a complete electronics analysis chain for each pixel in such a way that each pixel is able to suppress the noise by using a threshold set in energy, and then to count and to store the selected photons on its own. This electronics is embedded in a dedicated integrated circuit connected pixel by pixel on a pixelized X-ray sensor. As shown on the side picture, the photons are directly converted in the semi-conductor sensor, resulting in the creation of electric charges that are read out by the micro- electronics circuit. Unlike the CCDs, the XPAD detectors proceed by direct detection and do not need a scintillator nor optical fibers. Moreover, they count photons one by one, instead of integrating an X-ray fluence. These two properties allow for providing a much sharper PSF function without blooming effect.

Pépinière de Luminy avenue de Luminy - case Marseille – 9 Innovation XPAD hybrid pixel detector As an example the following features of the XPAD detectors are not available with CCDs and CMOS pixels:  Noise suppression  Energy selection  Almost infinite dynamic range  High Detection Quantum Efficiency (DQE(0) ≈ 100%, dose reduction)  Ultra fast electronic shutter (10 ns)  Frame rate ~ 1 kHz XPAD hybrid pixel detector Significant advantages of the XPAD, in particular considering the high dynamic range and the high frame rate, draw the interest of the professionals in material sciences (crystallography), who are working with laboratory sources as well as with high luminosity synchrotron beam light. The high quantum efficiency and the energy selection is prominent for biomedical imaging applications, since this allows for dose reduction and multi contrast agent imaging (color CT). The XPAD detectors benefit from the hybrid pixel technology, which leads to major advantages with regards to the present detectors in use. These advantages are mainly provided by direct photon conversion and real time electronics analysis of the X-ray photons, allowing for direct photon counting. Moreover, the sensor material can be adapted to the range of energies of the impinging X- ray photons that is driven by the application.

Pépinière de Luminy avenue de Luminy - case Marseille – 10 The markets All X-ray imaging field will benefit from the XPAD technology, thus opening a number of markets for the imXPAD company. Any imaging process will find several advantageous features in the list of specifications of the XPAD detectors, as shown in the table given below. Color CT X-ray tubes crystallography Synchrotron crystallography > 500 Hz

Pépinière de Luminy avenue de Luminy - case Marseille – 11 Products: XPAD 130 kpixels Silicon detector Specifications Dynamic range32 bits: 1/ 4 x 10 9 Counting rate per pixel5 x 10 5 cps (3 x 10 7 cps/mm 2 ) Energy range keV Quantum 9 keV 15 keV (measured) Energy resolution1 keV Threshold range5-30 keV Threshold dispersion150 eV Readout time2 ms Framing rate500 Hz Point-spread function1 pixel CoolingAir cooled Power consumption14 W Dimensions Pixel size130 x 130 µm 2 Pixels number (560 x 240) pixels Area75 x 30 mm 2 Sensor thickness500 µm Number of modules1 (no inactive gap) Overall dimensions (WHD) 120 x 110 x 180 mm 3 Weight 3 kg Economic and plug and play silicon pixel detector for synchrotron beam light as well as laboratory X-ray tube applications. The XPAD 130 kpixels is fully powered and interfaced. Just plug it on a PC. DAQ software is included with the detector delivery.

Pépinière de Luminy avenue de Luminy - case Marseille – 12 Products: XPAD 340 kpixels Silicon detector Fast medium size silicon pixel detector. In the standard version the modules are tiled (inclined by 7°) which saves significantly the dead area but it can also be assembled flat on request. The XPAD 340 kpixels is delivered ready to use with the complete readout system (PC-interfaces, optical fibers and dedicated PC) and the DAQ software. Specifications Dynamic range 32 bits: 1/ 4 x 10 9 Counting rate per pixel 5 x 10 5 cps (3 x 10 7 cps/mm 2 ) Energy range keV Quantum efficiency 9 keV: 99%, 15 keV: 70% (measured) Energy resolution 1 keV Threshold range 5-30 kV Threshold dispersion 150 eV Readout time 2 ms Framing rate 500 Hz Point-spread function 1 pixel Cooling Air-cooled Power consumption 30 or 45 W Dimensions Pixel size 130 x 130 µm 2 Pixels number ( 560 x 600) pixels Area 75 x 75 mm 2 Sensor thickness 500 µm Number of modules 5 or 8 Gaps x=0, y=4pixels, 1,6% of total area Overall dimensions (WHD) 135 x 230 x 250 mm 3 Weight 4,5 kg

Pépinière de Luminy avenue de Luminy - case Marseille – 13 Products: XPAD 540 kpixels Silicon detector Fast medium size silicon pixel detector. In the standard version the modules are tiled (inclined by 7°) which saves significantly the dead area but it can also be assembled flat on request. The XPAD 540 kpixels is delivered with the complete readout system (PC- interfaces, optical fibers and dedicated PC) and the DAQ software. Specifications Dynamic range 32 bits: 1/ 4 x 10 9 Counting rate per pixel 5 x 10 5 cps (3 x 10 7 cps/mm 2 ) Energy range keV Quantum efficiency 9 keV: 99%, 15 keV: 70% (measured) Energy resolution 1 keV Threshold range 5-30 kV Threshold dispersion 150 eV Readout time 2 ms Framing rate 500 Hz Point-spread function 1 pixel Cooling Air-cooled Power consumption 30 or 45 W Dimensions Pixel size 130 x 130 µm 2 Pixels number ( 560 x 960) pixels Area 75 x 120 mm 2 Sensor thickness 500 µm Number of modules 5 or 8 Gaps x=0, y=4pixels, 2,9% of total area Overall dimensions (WHD) 135 x 230 x 250 mm 3 Weight 5 kg

Pépinière de Luminy avenue de Luminy - case Marseille – 14 Products: XPAD 40 kpixels CdTe detector Specifications Dynamic range32 bits: 1/ 4 x 10 9 Counting rate per pixel5 x 10 5 cps (3 x 10 7 cps/mm 2 ) Energy range keV Quantum 15 keV, 35 keV (measured) Energy resolution600 eV Adjustable threshold range8-70 keV Threshold dispersion180 eV Readout time2 ms Framing rate500 Hz Point-spread function1 pixel CoolingAir cooled Power consumption10 W Dimensions Pixel size130 x 130 µm 2 Pixels number38400 (160 x 240) pixels Area20 x 30 mm 2 Sensor thickness700 µm Number of modules1 (no gap) Overall dimensions (WHD) 120 x 110 x 180 mm 3 Weight < 3 kg Economic and plug and play CdTe pixel detector for synchrotron beam light as well as laboratory X-ray tube applications. The XPAD 50 kpixels CdTe is fully powered and interfaced. Just plug it on a PC. DAQ software is included with the detector.

Pépinière de Luminy avenue de Luminy - case Marseille – 15 Since 1991, hybrid pixel detectors are being developed at CPPM for micro vertex trackers in high energy physics experiments. In 1996 the first hybrid pixel detector (in the world) was installed in the heart of the DELPHI (LEP, CERN, Geneva) experiment, under the direction of P. Delpierre, project leader. More recently, a vertex detector (2 m 2 of Si hybrid pixels) has been installed in the heart of the ATLAS experiment on the Large Hadron Collider (LHC) at CERN (Geneva, Switzerland). The origin of the XPAD technology From the performance of the DELPHI pixel detector, it became obvious that the photon counting technology can also be applied to X-ray imaging and bring significant improvement. In 1998, the CPPM team working on the development of hybrid pixels started to develop a dedicated pixelized micro-electronics circuit for X- ray imaging. One year later the XPAD1 detector was born.

Pépinière de Luminy avenue de Luminy - case Marseille – 16 Fabrication of the first XPAD detectors After some improvements, the XPAD2 circuit was produced and a large area (6,5 x 6 cm 2 ) detector was built. At that time, it was the largest hybrid pixel detector in the world. It has been widely tested at the ESRF/CRG-D2AM beam line in Grenoble, and then at the new synchrotron SOLEIL near Saclay. To assess the added value of hybrid pixels for biomedical imaging, a micro-CT scanner named PIXSCAN was developed at CPPM using the XPAD2 detector. The third version of the detector named XPAD3 was developed in collaboration with the Néel/ESRF laboratory and the detector group of the synchrotron SOLEIL. Several large size (7.5 x 12 cm 2 ) detectors have been produced at CPPM together with the associated software. These detectors have been largely tested on synchrotron beams as well as on the PIXSCAN micro-CT scanner. As a result, the XPAD technology is now ready for industrialization.

Pépinière de Luminy avenue de Luminy - case Marseille – 17 XPAD detectors versus CCD on synchrotron experiments Diffusion by a quasi-crystal of AlPdMn (courtesy: NEEL-CNRS/D2AM-CRG/ESRF, Grenoble, France) The large high dynamic range of XPAD detectors allows to observe simultaneously the high intensity Bragg peak and diffuse structures that shows the intrinsic “disorder” characteristic of quasi crystals. Moreover, the data obtained with the XPAD detector follow a pure Poisson statistics (σ = 26 for photons), which results from photon counting and helps their physical interpretation.

Pépinière de Luminy avenue de Luminy - case Marseille – 18 The XPAD detectors at SOLEIL RECIPROCAL SPACE TOMOGRAPHY (courtesy: SOLEIL/DiffAbs, Saint Aubin, France)‏ High resolution X-ray diffraction experiments on highly distorted semiconductor layers have strong experimental requirements: measuring the weak scattering from defects as well as the main diffraction peaks which might be more intense by 6 orders of magnitude. Aim : to characterize distortions in a GaInAs layer epitaxially grown on a GaAs single crystal surface : these strains modify the electronic properties. They also enlarge the small peaks associated with defects that are located near major crystal peaks, here (111). This type of experiments can not be performed with CCD’s. They are commonly done using crossed slits and scintillation counters by scanning each point, thus wasting a large amount of time (typically a factor 100) as compared when using the XPAD detector.

Pépinière de Luminy avenue de Luminy - case Marseille – 19 The XPAD detector for biomedical imaging Cone beam scans with the PIXSCAN micro-CT scanners (courtesy: imXgam team, CPPM) Improvements in medical imaging are expected thanks the XPAD detectors:  Large DQE conferred by an optimal efficiency that results from the use of high density sensor material, thus aiming at dose reduction  High speed data acquisition and high frame rate  Improved contrast thanks the exceptional noise free and energy selection properties of the XPAD detectors that allows for the subtraction of image taken at different energies before and after the absorption edges of contrast agents. To test these properties, two micro-CT scanners have been built at CPPM. The first scanner was using the XPAD2 detector (figure a), whereas the second one is using the XPAD3 detector (figure b and c). b) a) c)

Pépinière de Luminy avenue de Luminy - case Marseille – 20 Tumor growth monitoring Monitoring tumor mass expansion from repeated imaging sessions every 3-4 days from the second week post injection (D14 to D24). Maximum section of the tumor has been underlined (yellow) and its area was plotted versus time (courtesy: F. Debarbieux, IBDML, France). The XPAD detector for tumor growth study Dose reduction Because of the large DQE of the XPAD detector, low dose CT scans are possible. As an example, with 10 mGy only (more than 20 times less than the usual dose for small animal CT) a lung tumor is still visible (yellow arrow). This allows for repeated examinations of the same mouse. D14D18D21 D24 Tumor area evolution Day post injection Tumor maximal area

Pépinière de Luminy avenue de Luminy - case Marseille – 21 The XPAD detector for cancer research Simultaneous PET/CT images of a dead mouse with an inserted 22 Na sealed source done with the ClearPET/XPAD prototype. The imXgam research team at CPPM succeeded a simultaneous PET/CT scan of a mouse. Positron Emission Tomography (PET) allows for imaging tumors, whereas X-ray CT scans the anatomy. Fusion of PET and CT images are used to localize the position of the tumors with respect to the anatomy. Sate-of-the art PET/CT scanners do not allow to acquire PET and CT data at the same time. If the patient of the animal moves between the two examinations (even by breathing) the fusion of the images might not be precise. Simultaneous PET/CT scans are true co- registration of both modalities. Ultimately, CT images can be used to correct for respiratory or cardiac movements On the picture Kidneys and lungs are segmented and appear grey. The left image shows only the CT data (volume rendering of the 22 Na salt bullet and bones), the right image shows PET data (in red) fused with CT data (courtesy: imXgam team, CPPM).

Pépinière de Luminy avenue de Luminy - case Marseille – 22 How to contact us Contacts B. Dinkespiler, P.A. Delpierre Address imXPAD S.A.S. Pépinière du Grand Luminy Zone Luminy Entreprises CASE MARSEILLE Cedex 09 E.