Tom Janssens

Diagnostic guidelines for high-resolution melting curve (HRM) analysis: an interlaboratory validation of BRCA1 mutation scanning using the 96-well LightScanner.

Genetic analysis of BRCA1 by sequencing is often preceded by a scanning method like denaturing gradient gel electrophoresis (DGGE), protein truncation test (PTT) or DHPLC. High‐resolution melting curve (HRM) analysis is a promising and economical method for high‐throughput mutation scanning. The EuroGentest network (www.eurogentest.org) aims to assist with the introduction of novel technologies in the diagnostic setting. Therefore, we have performed a thorough and high‐standard interlaboratory evaluation and validation of HRM, in collaboration with Idaho Technology, the manufacturer of the LightScannerTM (LS). Through this detailed study of 170 variants, we have generated guidelines for easy setup and implementation of HRM as a scanning technique for new genes, which are adaptable to the quality system of an individual diagnostic laboratory. This validation study includes the description of a BRCA1‐specific mutation screening test using the 96‐well LS. This assay comprises 40 amplicons and was evaluated using a statistically significant elaborate panel of variants and control DNA samples. All heterozygous variants were detected. Moreover, genotype analysis for nine common polymorphisms created a fast screening and detection method for these frequently occurring nonpathogenic variants. A blind study using a total of 28 patient‐derived DNA samples resulted also in 100% detection and showed an average specificity of 98%, indicating a low incidence of false positives (FPs). Hum Mutat 30:1–11, 2009.

Diffusion, activation, and recrystallization of boron implanted in preamorphized and crystalline germanium

We have investigated diffusion and activation of boron implanted with 6 keV energy to a maximum concentration of 8.0×1020atoms∕cm3 in crystalline germanium (c-germanium) and preamorphized germanium, employing rapid thermal annealing in the range of 400–600 °C. As-implanted boron profiles in preamorphized germanium are shallower than the ones in c-germanium due to channeling suppression. While boron diffusion is not observed either in c-germanium or during the germanium regrowth from amorphous state, the boron activation level achieved from the two starting phases is significantly different. A boron activation level of 2.4×1020atoms∕cm3 has been found in regrown germanium, while a level of only 1.2×1019atoms∕cm3 is observed in c-germanium. Remarkably, there is no evidence of any residual extended defectivity at the original crystalline/amorphous interface, when preamorphization is performed.

Diffusion, activation, and regrowth behavior of high dose P implants in Ge

Time evolution of the chemical profile, electrical activity, and regrowth of P implanted in Ge at a concentration above the maximum equilibrium solubility is investigated at 500°C rapid thermal annealing temperature. During the first anneal, a second, epitaxial regrowth of a part of the amorphous layer leads to P trapping in substitutional sites at a level of about 4×1020atoms∕cm3. However, nonsubstitutional P atoms frozen in the crystal at high concentration during recrystallization form large, inactive precipitates of peculiar circular shape. Simultaneously, long annealing time leads to continuing, extensive P out- and indiffusion affecting both the P chemical profile and junction sheet resistance.

Shallow Junction Ion Implantation in Ge and Associated Defect Control

We have studied implant-induced damage, defect annealing, and recrystallization of B, Ga, P, As, and Sb introduced in Ge by ion implantation at high doses, such that dopant chemical concentrations are above the corresponding solubility in Ge, with energies that target about 100-nm junction depths. It is shown that the amount of damage induced in the Ge lattice increases with the mass of the implanted ion, as expected. Implanted B produces local amorphous regions, although crystalline Ge zones are present in the implanted layer. P is a self-amorphizing ion, creating a continuous amorphous layer during implantation. However, a low thermal budget is sufficient to fully regrow the amorphous layer, without evidence of residual extended defects, as evaluated by cross-sectional transmission electron microscopy. Conversely, high concentrations of As cause a significant decrease of the regrowth rate of the damaged layer during rapid thermal annealing in the 400-600°C range studied. Finally, high-dose implantation of heavy ions such as Sb induces dramatic morphologic changes in Ge that are not recovered by post-implant rapid thermal annealing.

Effect of amorphization and carbon co-doping on activation and diffusion of boron in silicon

We investigate the impact of amorphization and C co-implantation on B diffusion and activation properties after conventional spike rapid thermal annealing (RTA). We observe that after complete recrystallization at 600°C the B tail deepens by 5nm (at 5×1018at.∕cm3) due to B diffusion in a-Si. After spike RTA it becomes 12nm deeper with respect to an as-implanted profile, which proves that both diffusion mechanisms in a-Si and c-Si are important. However, the B diffusion in c-Si is sensitive to the fraction of substitutional C incorporated into c-Si. The best junction depth is Xj=16.5nm, with abruptness of 2nm/decade and Rs=583Ω∕◻.

Suppression of phosphorus diffusion by carbon co-implantation

The impact of Si interstitial (Sii) flux suppression on the formation of P junctions by rapid thermal annealing (RTA) is demonstrated. Here we investigate the role of amorphization coupled with C co-implantation on P diffusion and its activation. From experiments on C co-implants in a-Si versus c-Si, we conclude that only a small fraction of C interacts with Si interstitials (Sii). We have demonstrated that optimization of implants followed by spike RTA yields extensions suitable for gate lengths of 30nm, with vertical depth Xj=20nm (taken at 5×1018at.∕cm3), abruptness of 3nm/decade, and Rs=326Ω/◻.

Heavy ion implantation in Ge: Dramatic radiation induced morphology in Ge

High dose ion implantation of heavy elements in Ge induces a rough surface and profile distortions when measured with secondary ion mass spectrometry. In the case of Sb large subsurface holes are also induced by the implantation. The formation of these subsurface structures starts abruptly at a dose between 5∙1014 and 1015at∕cm2. The addition of a SiO2 capping layer on top of Ge prevents the formation of the surface roughness, but has limited impact on the void formation. These voids originate from vacancy clustering during the implant process. Anneal studies show that it is impossible to remove these structures by annealing, limiting the usefulness of high dose Sb implants in Ge for junction formation. In the case of As implantation a similar surface roughness is seen but no void formation. Adding a cap layer removes the surface roughness in this case and improves the secondary ion mass spectroscopy profiles.

CD248 and its cytoplasmic domain: A therapeutic target for arthritis

OBJECTIVE CD248 is a transmembrane glycoprotein expressed on the surface of activated perivascular and fibroblast-like cells. This study was undertaken to explore the function of CD248 and its cytoplasmic domain in arthritis. METHODS Synovial tissue biopsy samples from healthy controls, from patients with psoriatic arthritis (PsA), and from patients with rheumatoid arthritis (RA) were stained for CD248. Transgenic mice that were CD248-deficient (CD248-knockout [CD248(KO/KO) ]) or mice with CD248 lacking the cytoplasmic domain (CD248(CyD/CyD) ) were generated. Collagen antibody-induced arthritis (CAIA) was induced in these mice and in corresponding wild-type (WT) mice as controls. Clinical signs and histologic features of arthritis were evaluated. Cytokine levels were determined by enzyme-linked immunosorbent assay, and the number of infiltrating inflammatory cells was quantified by immunohistochemistry. In vitro studies were performed with fibroblasts from CD248-transgenic mouse embryos to explain the observed effects on inflammation. RESULTS Immunostaining of synovium from patients with PsA and patients with RA and that from mice after the induction of CAIA revealed strong CD248 expression in perivascular and fibroblast-like stromal cells. CD248(KO/KO) and CD248(CyD/CyD) mice had less severe arthritis, with lower plasma levels of proinflammatory cytokines, as compared with WT controls. Moreover, the joints of these mice had less synovial hyperplasia, reduced accumulation of inflammatory cells, and less articular cartilage and bone damage. Tumor necrosis factor α-induced monocyte adhesion to CD248(CyD/CyD) fibroblasts was impaired. CD248(CyD/CyD) fibroblasts exhibited reduced expression of hypoxia-inducible factor 1α, placental growth factor, vascular endothelial growth factor, and matrix metalloproteinase 9 activity in response to transforming growth factor β. CONCLUSION CD248 contributes to synovial hyperplasia and leukocyte accumulation in inflammatory arthritis, the effects of which are mediated partly via its cytoplasmic domain. CD248 is therefore a potential new target in the treatment of arthritis.

Active dopant characterization methodology for germanium

In order to reach the ITRS goals for future complementary metal-oxide semiconductor technologies there is a growing interest in using germanium as an alternative substrate material in view of its higher mobility. Different species and thermal budgets are presently being investigated in order to determine the most likely candidates for the required junction formation. A key issue is the accurate determination of the achievable electrical activation, i.e., the reliable measurement of the sheet resistance and electrical depth profile. In order to be applicable to Ge-based junctions, standard techniques such as the spreading resistance probe and scanning spreading resistance microscopy (SSRM) need to be reevaluated in terms of their performance and operational conditions. First, the significantly different behavior of germanium calibration curves (versus silicon) will be discussed. Next, the shape and characteristics of the probe imprints (Ge is softer than Si) and the differences in raw data behavior will be...

Screen-Printed Aluminum-Alloyed

We demonstrate the use of industrial-orientated screen-printed aluminum-alloyed emitter for high-efficiency n-type interdigitated back-contact silicon solar cells. Different cell designs with various pitch sizes and emitter fractions have been studied. With an improved front surface field (FSF), short-circuit current densities up to 40 can be obtained. By combining the best cell design and the improved FSF, a high conversion efficiency of 19.1% with Czochralski n-type material has been achieved.