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Clinical use of doxorubicin (Dox) is limited by cumulative myelo- and cardiotoxicity. This research focuses on the detailed characterization of PhAc-ALGP-Dox, a targeted tetrapeptide prodrug with a unique dual-step activation mechanism, designed to circumvent Dox-related toxicities and is ready for upcoming clinical investigation. Coupling Dox to a phosphonoacetyl (PhAc)-capped tetrapeptide forms the cell-impermeable, inactive compound, PhAc-ALGP-Dox. After extracellular cleavage by tumor-enriched thimet oligopeptidase-1 (THOP1), a cell-permeable but still biologically inactive dipeptide-conjugate is formed (GP-Dox), which is further processed intracellularly to Dox by fibroblast activation protein-alpha (FAPα) and/or dipeptidyl peptidase-4 (DPP4). In vitro, PhAc-ALGP-Dox is effective in various 2D- and 3D-cancer models, while showing improved safety toward normal epithelium, hematopoietic progenitors, and cardiomyocytes. In vivo, these results translate into a 10-fold higher tolerability and 5-fold greater retention of Dox in the tumor microenvironment compared with the parental drug. PhAc-ALGP-Dox demonstrates 63% to 96% tumor growth inhibition in preclinical models, an 8-fold improvement in efficacy in patient-derived xenograft (PDX) models, and reduced metastatic burden in a murine model of experimental lung metastasis, improving survival by 30%. The current findings highlight the potential clinical benefit of PhAc-ALGP-Dox, a targeted drug-conjugate with broad applicability, favorable tissue biodistribution, significantly improved tolerability, and tumor growth inhibition at primary and metastatic sites in numerous solid tumor models.

Clinical use of doxorubicin (Dox) is limited by cumulative myelo- and cardiotoxicity. This research focuses on the detailed characterization of PhAc-ALGP-Dox, a targeted tetrapeptide prodrug with a unique dual-step activation mechanism, designed to circumvent Dox-related toxicities and is ready for upcoming clinical investigation. Coupling Dox to a phosphonoacetyl (PhAc)-capped tetrapeptide forms the cell-impermeable, inactive compound, PhAc-ALGP-Dox. After extracellular cleavage by tumor-enriched thimet oligopeptidase-1 (THOP1), a cell-permeable but still biologically inactive dipeptide-conjugate is formed (GP-Dox), which is further processed intracellularly to Dox by fibroblast activation protein-alpha (FAPα) and/or dipeptidyl peptidase-4 (DPP4). In vitro, PhAc-ALGP-Dox is effective in various 2D- and 3D-cancer models, while showing improved safety toward normal epithelium, hematopoietic progenitors, and cardiomyocytes. In vivo, these results translate into a 10-fold higher tolerability and 5-fold greater retention of Dox in the tumor microenvironment compared with the parental drug. PhAc-ALGP-Dox demonstrates 63% to 96% tumor growth inhibition in preclinical models, an 8-fold improvement in efficacy in patient-derived xenograft (PDX) models, and reduced metastatic burden in a murine model of experimental lung metastasis, improving survival by 30%. The current findings highlight the potential clinical benefit of PhAc-ALGP-Dox, a targeted drug-conjugate with broad applicability, favorable tissue biodistribution, significantly improved tolerability, and tumor growth inhibition at primary and metastatic sites in numerous solid tumor models. ispartof: MOLECULAR CANCER THERAPEUTICS vol:21 issue:4 pages:568-581 ispartof: location:United States status: published

Process modeling approaches derived from CMOS industry are successfully applied in the Photovoltaic industry, in order to provide guidance on the design of the doped regions. The accurate prediction of the dopant diffusion and activation kinetics, as well the oxide growth rate, are essential for the adequate profile engineering. The latter is vital for a cost effective optimization of the cell operation. In addition, in the case of ion implantation, TCAD modeling is also necessary for the monitoring of the damage evolution and its optimized reduction. Indeed, high levels of residual defects are found to deteriorate the electrical properties of the doped regions, as they act as recombination centers for Shockley-Read-Hall recombination and thus limit the minority carrier lifetimes. Designing optimum anneal strategies is an important objective of the TCAD modeling approach. In this paper we are presenting an overview of our developments to optimize TCAD simulations for doped regions formation used in high efficiency crystalline silicon solar cells. The modeling studies cover the two major dopant techniques (tube diffusion and ion implantation) for each dopant (Boron and Phosphorus).

Purpose Retinal vein occlusions (RVO) are a major cause of vision loss in people aged 50 years and older. Current therapeutic options limit the consequences of RVO but do not eliminate the cause. Cannulation of the involved vessel and removal of the clot may provide a more permanent solution with a less demanding follow-up. However, cannulation of smaller retinal veins remains challenging. This paper explores the use of ocriplasmin (recombinant plasmin without its kringles) to clear RVO, using a robotic micromanipulator. Methods Branch RVO were induced in a porcine model with rose bengal followed by 532 nm endolaser to the superior venous branch of the optic nerve. The vein was cannulated proximal to the occlusion or beyond the first branching vessel from the obstruction. The vein was infused with a physiologic citric acid buffer solution (CAM) or CAM/ocriplasmin. The time of cannulation, number of attempts, and the ability to release the thrombus were recorded. Results Cannulation and infusion was possible in all the cases. The use of a micromanipulator allowed for a consistent cannulation of the retinal vein and positional stability allowed the vein to remain cannulated for up to 20 min. In none of the attempts (5/5) with CAM did the thrombus dissolve, despite repeat infusion/relaxation cycles. In 7/7 injections of CAM/ocriplasmin near to the point of obstruction, the clot started to dissolve within a few minutes of injection. An infusion, attempted beyond the first venous branch point proximal to the clot, was unsuccessful in 2/3 attempts. Conclusions Ocriplasmin is effective in resolving RVO if injected close to the site of occlusion with the use of a micromanipulator.

Author(s): de Smet, Marc; Meenink, Thijs; Janssens, Tom; Vanheukelom, Valerie; Naus, Gerrit; Beelen, Maarten; Meers, Caroline; Jonckx, Bart; Stassen, Jean-Marie | Abstract: PURPOSE: To develop a methodology for cannulating porcine retinal venules using a robotic assistive arm after inducing a retinal vein occlusion using the photosensitizer rose bengal. METHODOLOGY: Retinal vein occlusions proximal to the first vascular branch point were induced following intravenous injection of rose bengal by exposure to 532nm laser light delivered by slit-lamp or endolaser probe. Retinal veins were cannulated by positioning a glass catheter tip using a robotically controlled micromanipulator above venules with an outer diameter of 80μm or more and performing a preset piercing maneuver, controlled robotically. The ability of a balanced salt (BSS) solution to remove an occlusion by repeat distention of the retinal vein was also assessed. RESULTS: Cannulation using the preset piercing program was successful in 9 of 9 eyes. Piercing using the micromanipulator under manual control was successful in only 24 of 52 attempts, with several attempts leading to double piercing. The best location for cannulation was directly proximal to the occlusion. Infusion of BSS did not result in the resolution of the occlusion. CONCLUSION: Cannulation of venules using a robotic microassistive arm can be achieved with consistency, provided the piercing is robotically driven. The model appears robust enough to allow testing of therapeutic strategies aimed at eliminating a retinal vein thrombus and its evolution over time.

Recently, the interest for the implementation of local ion implantation for emitter formation has been renewed, as it results in high cell efficiencies [1] , while the amount of process steps is reduced. After implantation, a thermal diffusion (annealing) is necessary for the removal of the ion-induced damage, the activation of dopants and the formation of the desired profile shape. The goal is to change the implanted retrograde near surface (10-100 nm) inactive profile, into a damage free, box-like shaped, and fully active emitter (or BSF) with a low saturation current density (J 0e ). Here, we study different post-implantation annealing schemes, to achieve high performance boron emitters for n-type IBC solar cells. We show experimentally, that the use of oxygen gas during the boron anneal has an impact on the electrical performance (J0e) of the emitter. On the other hand, the obtained J0e values are higher than those obtained by the standard diffusion approach. Hence, in order to understand these results and optimize the implant/anneal process, the modeling of the profile shape and the damage evolution would be extremely valuable. In this work, we report on our initial simulation results, and we demonstrate the impact of oxygen on the evolution of the profile shapes of the implanted B-emitters after anneal, taking into account boron diffusion kinetics mechanisms such as Transient Enhanced Diffusion (TED) and Oxidation Enhanced Diffusion (OED). Moreover, we monitor the residual damage and we make a first effort to correlate the increase on the J0e values with the residual damage levels. Throughout this work, we adopt the process simulator tool Sentaurus Process.

In this work we investigate the potential of inline single side wet-etch processing for rear side emitter removal and edge isolation for large area p-type Passivated Emitter and Rear (PERC) silicon solar cells. We focus on the integration of this process in flows leading to shallow emitters and screen printed front contacts and to deep, highly ohmic emitters in association with Cu contacts. The inherent advantage of this process, beside high throughput, is the external gettering performed by full emitter etch at the rear side. This is particularly relevant in the case of two-step emitter formation process, where removal of phosphorus diffused layers is most effective when performed prior to the high temperature drive-in step. Another effect that we make use of is the front-side emitter etch back performed by the etch bath vapors, which can be used to tune the phosphorus surface concentration and thus the emitter sheet resistance. Using this process, we report efficiency up to 19.9% for CZ large-area, homogeneous-emitter, screen printed cells, and 20.4% for CZ, large-area Cu plated cells.

B implanted emitters are investigated in the back junction cell configuration and their material properties are tested in double side implanted Si wafers. B has been implanted at 5 keV at various dose conditions varying from 1 × 1014 up to 3 × 1015 at./cm2 and activated at 1000°C for 10 min. N-type 8 × 8 cm2 mono-crystalline cells are fabricated and measured. Both fill factor and efficiency increase for high-B doses. However, at 1015 at./cm2 B dose the Voc drops, which is in agreement with lifetime degradation in the wafer. Defect evolution simulations of BnIm clusters formation is correlated with lifetime degradation. Copyright © 2011 John Wiley & Sons, Ltd.

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 [CD248KO/KO]) or mice with CD248 lacking the cytoplasmic domain (CD248CyD/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. CD248KO/KO and CD248CyD/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 CD248CyD/CyD fibroblasts was impaired. CD248CyD/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.

Selecting a reversed phase liquid chromatographic (RP-LC) column with suitable selectivity for a particular separation is difficult if the brand name of the column is not known. Monographs of the European Pharmacopoeia and other official compendia for drug analysis only give a general description of the stationary phase to be used for a liquid chromatographic method. A project to develop a chromatographic test procedure to characterise RP-LC C18 columns was started earlier and resulted in a fast, simple, repeatable, and reproducible test procedure. Four column parameters allowed the characterisation and ranking of these columns. In this paper, the separations of three drug substances (amlodipine, tetracaine, and bisacodyl) from their respective impurities were examined applied on 77 RP-LC columns. It was observed, that the column ranking system was helpful in the selection of a suitable column for the separation of amlodipineand tetracaine, but also showed its limitations towards the separation o...

The increasing complexity of semiconductor devices imposes challenging requirements on particle contamination and surface damage. To meet these requirements novel surface-cleaning processes are evaluated, which combine physical energy with organic solvents. In this work, the performance of megasonic cleaning with deionized water (DIW) and N-methylpyrrolidone (NMP) was evaluated in terms of particle removal efficiency (PRE) and damage analysis. The goal was to define an optimum process window where the PRE was maximum and the damage was minimum. Particle removal and damage analysis were performed on unpatterned silicon wafers and with patterned polysilicon lines, respectively, under identical sonic power and process parameters. A comparison between these two solvents reveals that at low sonic power the particle-cleaning performances in DIW and NMP are similar. At high sonic power, in both solvents a detailed analysis of the PRE and damage indicates a non-homogeneous trend over the surface of the wafer. Mor...

High velocity aerosol cleaning using ultrapure water or dilute aqueous solutions (e.g. dilute ammonia) is common in semiconductor IC fabrication [1]. This process combines droplet impact forces with continuous liquid flow for improved cleaning efficiency of sub-100nm particles. As with any physically enhanced cleaning process, improved particle removal can be accompanied by increased substrate damage, especially to smaller (

Accurate modeling of the enhancement of the ionization probabilities of secondary ions (positive and negative) by the presence of reactive species requires a precise determination of their concentration at the outermost surface and thus a fundamental understanding of their incorporation and release processes. In the present paper we discuss these processes for oxygen, cesium and cluster ion bombardment with a special emphasis on their importance at (very) low bombardment energies. At these energies the sputtering processes becomes very small and deposition instead of erosion is predicted while for some species such as oxygen and cesium, an additional process, i.e. desorption, becomes more important thereby enabling a stationary state without deposition. The desorption process is a property of the primary ion and element specific and can be predicted based on the sputter yields and heat of sublimation. For those species/conditions where desorption is not operational (such as for C 60 -beams), depth profiling at very low energies and with low sputter yields ( 5 ) n -bombardment and the positive impact of oxygen flooding on C 60 bombardment can all be explained when the desorption mechanism is included in the balance equation.

The local particle removal efficiency (PRE) of nano particles in megasonic cleaning experiments is studied. This approach makes it possible to quantify non uniform cleaning effects over the wafer and to look into the dynamics of particle removal at different areas on the wafer. A direct correlation between PRE and megasonic induced damage of device structures demonstrates that a considerable amount of damage is already formed at less efficiently cleaned areas of the wafer.

Physical-cleaning technologies are usually evaluated by comparing the particle removal efficiency (PRE) on blanket wafer with damage formation on fragile structures, typically gate stack type structures. However, patterned wafers provide a more realistic cleaning challenge. Particle removal efficiencies from micron-wide and -deep trenches have been evaluated using highvelocity-aerosol cleaning. When using short cleaning times, i.e. 1 scan of approximately 5s, a decrease in cleaning efficiency is found for even modest pattern dimensions compared to blanket wafers. By extending the cleaning time, i.e. increasing the number of scans, cleaning efficiencies comparable to blanket-wafer tests can be reached. These results are compared with cleaning efficiencies obtained in a megasonic cleaning tank. Introduction Due to the stringent specifications for substrate loss [1], chemical cleaning has to be assisted by physical forces to enable the removal of particles. Recently high-velocityaerosol cleaning was shown to provide a good balance between particle removal efficiency (PRE) and damage [2] and to outperform a number of megasonic cleaning systems for the removal of 78nm silica particles versus damaging to 70nm gate-stack lines. [3] However these particle removal efficiencies are determined on blanket wafers while ‘real’ cleaning steps are performed on patterned wafers. Differences between cleaning of blanket and patterned wafers have already been studied. [4] However these patterns consisted of very large structures, where the pattern dimensions largely exceeded the cleaning-event size, i.e. the 3μm bubble radius for megasonic cleaning at 1MHz. Also recently a decrease in PRE has been shown upon megasonic tank cleaning of micron-sized features. [5] For high-velocity-aerosol cleaning the cleaning events consist of large droplets (10-100μm) impacting on the surface. [6] The cleaning mechanism for high-velocityaerosol cleaning is described by sideways jetting during the impact of a droplet on a surface. This sideways jetting is parallel to the substrate compared to the perpendicular jetting due the asymmetric collapse of a bubble during megasonic cleaning. This might suggest that the PRE of high-velocity-aerosol cleaning might be influenced even more by the presence of patterns on the wafer compared to megasonic (tank) cleaning. Experimental The particle removal efficiency (PRE) of high-velocity aerosol cleaning (DNS Nanospray) has been evaluated for 10, 3 or 1μm wide, 1 or 2.2μm deep trenches in silicon. The wafers were contaminated with 350nm large silica particles. Prior to contamination the wafers received an O3-last clean. The particles were detected using a darkfield-inspection tool (KLA-Tencor AIT). Results Figure 1 shows the PRE as a function of the aspect ratio (depth divided by width) for high-velocity-aerosol cleaning. The PRE data for the megasonic system have been taken from Ref. 5. Both cleaning techniques show a more than 10% decrease in particle removal efficiency for the 1μm wide, 2.2μm deep trenches compared to blanket wafers. Megasonic and aerosol cleaning show a similar drop in cleaning efficiency. By reducing the number of scans for high-velocityaerosol cleaning, we were able to evaluate changes in cleaning efficiency for even modest trench dimensions (aspect ratio < 1). The results show that already for these aspect ratios the particle removal efficiency for particles inside the trenches is substantially lower than on blanket wafers. However the cleaning efficiency can be recovered by extending the number of scans. Conclusion We can conclude that patterned wafers can be cleaned by high-velocity aerosols. However the removal of particles from patterned wafers proves to be more difficult than their removal from blanket wafers. References: [1] International Technology Roadmap for Semiconductors 2006 update, Front end processes, p. 9 [2] H. Hirano et al. Electrochem. Solid-State Lett., Vol. 9 (2006) p. G62 [3] G. Vereecke et al. UCPSS 2006, to be published in Solid State Technology [4] K. Bakhtari et al. J. Electrochem. Soc. Vol. 153 (2006) p. C603 [5] K. Wostyn et al. UCPSS 2006, to be published in Solid State Technology [6] S. Verhaverbeke, Sematech Surface Preparation and Cleaning Conference 2005 Figure 1: The particle removal efficiency (PRE) normalized to the PRE as determined on blanket wafers. The open circles show the results for high-velocity aerosol cleaning. The open triangles show the results for megasonic cleaning and were taken from Ref. 5.

In this paper, particle removal experiments from silicon wafers in organic solvent using megasonic energy are presented. Nanoparticles are first deposited on Si wafers via controlled-contamination process. The particle removal efficiency as a function of megasonic power is studied both for freshly-deposited and aged particles. Several cleaning recipes are evaluated, by changing the processing conditions and rinsing time/chemistry. When low megasonic power is used, particles are found to cluster and re-deposit on the wafer surface after being detached. This phenomenon could be explained by charging phenomena of particles and silicon surfaces in the specific solvent. A surfactant is added to prevent clustering and re-deposition, leading to a noticeably improvement in particle removal efficiency.

As the semiconductor industry moves to processes for line widths of 65nm and beyond, there is the need for a new cleaning scheme addressing various new issues of the nano world. The ongoing trend to lower concentration mixtures in critical wafer cleaning now comes to its ultimate climax by reducing the concentration down to a single digit ppm level, and then to ultra low concentrations far below 1 ppm, making use of a whole new part of physics: Quantum Electro Dynamics and the formation of “clusters”. First we will outline the nature and the benign behaviour of the “clusters”. The study focuses on the inline test results of the first clustered clean application in semiconductor manufacturing environment enabling us to compare the performance of the clustered clean to the standard RCA clean of the fab. Clusters formation of ions in very dilute solutions and their physical properties has been described by Shui-Yin Lo [1,2] in 1996. Once the Megasonics energy has detached the particles off the surface, the clustered water holds the particles in the fluid as it is creating a zeta potential between the wafer surface and the now liquid borne particles. Thus, preventing a redeposition on the wafer surface, the particles now can be transported off the Processing area by overflow rinse. The scope of this work was to prove and compare the Particle Removal Efficiency (PRE) of this new cleaning method with standard RCA Clean.

We have investigated flash-lamp annealing (FLA) of germanium wafers doped with phosphorous and boron introduced in the crystal by ion implantation. Annealing was performed by using pre-heating at 400–450 °C in a conventional rapid thermal processing (RTP) unit and a fast (3–20 ms) FLA annealing at 800 °C or 900 °C. Diffusion of P is suppressed during the 800 °C–20 ms FLA annealing, while concentration-enhanced diffusion occurs upon 900 °C FLA anneals. Importantly, in both cases P activation seems to be enhanced by the FLA process. However, junction stability following the FLA process and possible deactivation are a concern. In contrast, the FLA process applied to B-doped pre-amorphized Ge layers does not show advantages as compared to a RTP conventional annealing combined with a solid phase epitaxial regrowth, in terms of B activation level.

Within this work, we have studied ultrathin n- and p-type extension implants in order to evaluate the junction delineation accuracy and reproducibility of the SSRM technique on ultra-shallow implants. This is a challenging task since it needs a technique that has simultaneously good sensitivity (

The use of an internal O18 implant to quantify the surface oxygen concentration, presented in Franzreb et al. [K. Franzreb, J. Lorincik, P. Williams, Surf. Sci. 573 (2) (2004) 291], is critically evaluated, in particular when applied for bombardment conditions leading to high depth resolution measurements. It is shown that this methodology gives no direct access to the surface composition, but only to the O/Si ratio in the total emission flux, ϕO16/ϕSi, which reflects the total amount of oxygen that passes through the surface. When applied under conditions relevant for high depth resolution studies (oxygen bombardment at low energies and small angles), extremely large ϕO16/ϕSi -ratios are observed (>50). These large values are interpreted in terms of the oxygen that leaves the surface by sputtering as well as by alternative processes such as by desorption. The latter is included in the total flux ratio ϕO16/ϕSi, but has little interaction with the sample surface and the departing Si-atoms. Therefore the use of these ϕO16/ϕSi ratios in ionization mechanism studies becomes inappropriate unless the desorbed oxygen fraction ϕ O desorb can be calculated quantitatively or is negligible. Based on the angular dependence of the useful ion yield of oxygen, we make a rough estimate of the desorbed oxygen fraction ϕ O desorb and show that this becomes a dominant fraction (up to 70%) in the emitted flux at low bombardment energies.

Chemotherapy induced nail toxicity is observed in up to 88 % of cancer patients. Onycholysis, a severe form of nail toxicity in which the nail is detached from the nail bed, is observed in 0 % to 44 % of cancer patients undergoing a taxanes based chemotherapy. The use of ice gloves may reduce incidence rates for chemotherapy induced onycholysis, but cause cold and pain. In this research it was hypothesized that the use of local active cooling would reduce blood flow in the distal phalanxes, whilst inducing less discomfort as compared to an ice glove.

Epitaxial fully strained Si films are known to form an effective passivation of the Ge(1 0 0) surface. However, we show using low-energy secondary ion mass spectrometry (SIMS) that considerable Ge surface segregation occurs for Si films grown from SiH 4 at 500 °C. In this study, we develop an alternative deposition process at 350 °C using Si 3 H 8 which significantly decreases the Ge peak at the Si surface. We attribute this strong reduction mainly to the fact that growth at 350 °C from trisilane proceeds below the Si–H desorption temperature. Charge pumping measurements on n-type Ge devices show a reduction by approximately a factor three in the high-k/substrate interface trap density for the samples with 350 °C Si passivation, compared to those using a Si passivation deposited at 500 °C.

This paper provides an overview of the current state-of-the-art in the formation of shallow junctions in germanium by ion implantation, covering the issues of dopant activation, diffusion and defect removal. As will be shown, for the case of p + implantations, the application of rapid thermal annealing (RTA) to B implants yields good sheet resistance values, corresponding with activation levels well above the maximum solid solubility. A further improvement can be achieved by the use of a Ge pre-amorphization implant (PAI), which also removes the stable extended defects observed after high-dose B implantations. It will be shown that the formation of shallow n + junctions is a more challenging field due to the rather low dopant solubilities and high diffusivities. However, encouraging results will be reported on the application of laser and flash-lamp annealing of P implantations in Ge. Also point-defect engineering is shown to be successful in controlling the junction formation.

The analysis of thin films in the range of 10 nm and less has become very important in microelectronics. The goal of this article is an evaluation of low-energy TOF-ERDA (time-of-flight elastic recoil detection analysis) in comparison with low-energy SIMS (secondary ion mass spectrometry) and HRBS (high-resolution Rutherford backscattering spectrometry), using a thin SiO 2 /Si 3 N 4 /SiO 2 stack as a test vehicle. Comparisons are made on the depth resolution, its loss as a function of depth and the quantification accuracy.

To understand negative ion formation under Cs + bombardment, we have studied the steady-state Cs depth distribution in Si and Ge with a focus on high-resolution analysis conditions i.e. Cs + energies between 500 eV and 5 keV and impact angles from 0° to 60°. The in situ internal Cs depth profiles have been measured with a low energy O 2 + beam (0.5–1 keV) similar to the work of Yoshikawa [S. Yoshikawa, H. Morita, et al., Appl. Surf. Sci. 203–204 (2003) 252–255]. To minimize the distortions on Cs profiles, a non-oxidizing condition (at impact angle 60°) was chosen instead of an oxidizing condition. The internal Cs profiles in Si have a flat saturation region near the surface, with an intensity independent from the bombardment conditions. Only the profile width scales with impact angles and energies. Whereas in the Ge-case, a Gaussian profile is always obtained. Based on the internal Cs profiles, a possible near surface altered layer formation in Si and Ge under Cs bombardment is suggested.

In this paper, we demonstrate the consequences of extension junction formation by low-temperature solid-phase-epitaxial-regrowth in nMOS transistors. Atomistic simulations, experimental device results, sheet resistance, and scanning spreading resistance microscopy data indicate that the high concentration of silicon interstitials associated with the end-of-range defect band promote the local formation of boron-interstitial clusters, and thus deactivate boron in the pocket and channel. These inactive clusters will dissolve after the high concentration silicon interstitial region of the end-of-range defect band has been annihilated. This nMOS requirement is in direct opposition to the pMOS case where avoidance of defect band dissolution is desired, to prevent deactivation of the high concentration boron extension profile.

The formation of shallow junctions in germanium substrates, compatible with deep submicron CMOS processing is discussed with respect to dopant diffusion and activation and damage removal. Examples will be discussed for B and Ga and for P and As, as typical p- and n-type dopants, respectively. While 1 to 60 s Rapid Thermal Annealing at temperatures in the range 400-650oC have been utilized, in most cases, no residual extended defects have been observed by RBS and TEM. It is shown that 100% activation of B can be achieved in combination with a Ge pre-amorphisation implant. Full activation of a P-implant can also be obtained for low-dose implantations, corresponding with immobile profiles. On the other hand, for a dose above the threshold for amorphisation, a concentration-enhanced diffusion of P occurs, while a lower percentage of activation is observed. At the same time, dose loss by P out-diffusion occurs, which can be limited by employing a SiO2 cap layer.

Understanding dopant diffusion and activation mechanisms is a key issue for future sub-45 nm CMOS technologies. This understanding requires the availability of accurate chemical and electrically active dopant profiles. In this work we will focus on the accurate characterization of the electrical active portion of ultra-shallow junction (USJ) profiles, including a precise sheet resistance determination. Here, we will discuss respectively, sheet resistance measurements with conventional and low weight four point probe (FPP) systems, electrical depth profiling by the spreading resistance probe (SRP), alternative solutions based on probe-spacing experiments with an SRP-tool, and electrical characterization by non-contact, non-destructive optical tools, such as surface voltage based resistance and leakage (RsL) measurements, carrier illumination (CI) and infra-red spectroscopic ellipsometry (IR-SE). The comparison will mainly be based on state-of-the-art, low temperature, 1–2 nm/decade, sub-50 nm depth, chemical vapor deposition (CVD) layers with different thicknesses and dopant levels. Furthermore the activation of boron in solid phase epitaxially regrown (SPER) source-drain structures will be discussed. It will be illustrated that the combination of electrical characterization tools can supply essential information not otherwise obtainable through other means such as secondary ion mass spectrometry (SIMS) chemical profiling.

To get an insight in the diffusion behavior of dopants such as arsenic and boron after annealing and in particular their segregation characteristics towards the interface in oxide structures on silicon, it is necessary to probe the dopant profile with very high accuracy and depth resolution. Sputter depth profiling as employed in secondary ion mass spectrometry (SIMS) is frequently used as the most suited tool for dopant profiling in view of its sensitivity and depth resolution. However in order to determine the segregated arsenic/boron peak, sub-nanometer depth resolution is required and artifacts such as beam induced broadening effects, potential ionization yield changes at interfaces, transient sputter yields need to be considered in detail. When reducing the primary beam energy the depth resolution can be improved and sub-nanometer depth sensitivity can be demonstrated. However comparisons with high resolution elastic recoil detection analysis demonstrate that it is at present impossible to obtain a reliable depth profile in the first nanometer near the surface nor even in the oxide part of the profile, where no ionization nor sputter yield transients are expected. Enhanced beam induced migration of boron during the initial phase of the bombardment needs to be invoked to explain the results. The latter appears to be enhanced under conditions (∼normal incidence) where full oxidation occurs.

The determination of the oxygen concentration at the surface is the critical parameter in all models [Surf. Sci. 112 (1981) 168; Nucl. Instrum. Meth. Phys. Res. B 14 (1986) 403; in: A. Benninghoven, B. Hagenhoff, H.W. Werner (Eds.), SIMS, Vol. X, Wiley, New York, 1997, 203 pp.; Phys. Rev. B 50 (1994) 15015; in: A. Benninghoven, P. Bertrand, H.N. Migeon, H.W. Werner (Eds.), SIMS, Vol. XII, Elsevier, Amsterdam, 2000, 151 pp.; J. Appl. Phys. 90 (2001) 4456] that study the large enhancement of the ionisation probability of positive ions by the presence of oxygen at the surface. Different analysis techniques (low energy ion scattering, Rutherford back scattering spectrometry and secondary ion mass spectrometry) are combined in order to clarify the oxygen dependence of the ionisation probability of Si+, αSi+, during O2+ bombardment. A ratio of ion signals is correlated with the surface oxygen content, determined by LEIS, allowing us to study the enhancement of the ionisation probability of Si by oxygen at the surface for energies between 1 and 5 keV per O2+ ion. For a wide range of oxidation conditions the oxygen enhancement can be described by a power law dependence on the oxygen content αSi+∝(CO/CSi)3.24, whereby the power shows no significant energy dependence for the studied energy range. The steep enhancement of the ionisation probability at high oxygen content, which is energy dependent, can be correlated to a change in the surface structure: enhanced shadowing of silicon by oxygen, observed by LEIS.

By combining in situ SIMS/RBS measurements, sputter yields variations and ionisation probability variations were measured in the transient region of a poly-Si 0.8 Ge 0.2 layer bombarded with 12 keV O 2 + at normal incidence. The goal of the experiment is to investigate if the prepeak in the Ge + SIMS signal could be explained by sputter yield variations. The result of the experiment shows a minimum in the sputter yield variation of Ge during the build-up of the altered layer, which does not coincide with the minimum of the Ge + -signal. This suggests that the prepeak is not only a sputter yield effect but also due to a change in ionisation probability.

To get an insight in the diffusion behavior of boron after annealing and in particular its segregation characteristics towards the interface in oxide structures on silicon, it is necessary to probe the boron profile with very high accuracy and depth resolution. Sputter depth profiling as employed in secondary ion mass spectrometry (SIMS) is frequently used as the most suited tool for dopant profiling in view of its sensitivity and depth resolution. However, in order to determine the segregated boron peak, sub-nm depth resolution is required and artifacts such as beam induced broadening effects, potential ionization yield changes at interfaces, transient sputter yields need to be considered in detail. When reducing the primary beam energy the depth resolution can be improved and sub-nm depth sensitivity can be demonstrated. However, comparisons with high-resolution elastic recoil detection analysis demonstrate that even under those conditions no reliable depth profile can be obtained in the first nm near the surface nor even in the oxide part of the profile, where no ionization nor sputter yield transients are expected. Enhanced beam induced migration of boron during the initial phase of the bombardment needs to be invoked to explain the results.

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.

The impact on the metal gate effective work function (EWF) of As ion implantation through TiN/TaN/HfO2 gate stack was investigated. An As implantation at 20 KeV reduces the flat-band voltage (VFB) for TiN/TaN/HfO2 capacitors (or equivalently reduces the EWF) by a maximum of 600 mV at a dose of 5×1015 cm-2. This VFB reduction is correlated to the As pile-up at the TaN–HfO2 interface, as evidenced by a secondary ion mass spectroscopy (SIMS) study. The As ion accumulation at the interface of the gate electrode–dielectric interface is suggested to induce an interface dipole, contributing to the observed phenomena.

A systematic study of the modulation of the workfunction (WF) of Ni fully silicided gates by doping is presented, comparing the effects of dopants (Al, B, undoped, P, and As) on the WF for different dielectrics (SiO/sub 2/ versus HfSiON) and silicide phases (NiSi, Ni/sub 2/Si and Ni/sub 31/Si/sub 12/). Dual thickness series (HfSiON/SiO/sub 2/) were used to extract accurate WF values accounting for charge effects on HfSiON. While a WF modulation in the range of /spl sim/0.4 V was obtained for NiSi on SiO/sub 2/ comparing As, P, and B doped and undoped devices, negligible modulation was obtained for NiSi on HfSiON (/spl les/50 mV) suggesting Fermi-level pinning, and for the Ni-rich silicides on SiO/sub 2/ (/spl les/100 mV). Dopant pileup at the dielectric interface, believed to be responsible for the NiSi/SiO/sub 2/ WF modulation, was, however, observed for both NiSi and Ni-rich silicides. In contrast the WF of Ni-rich silicides on SiO/sub 2/ can be modulated with Al, suggesting a different mechanism of WF tuning for Al compared to B, P, and As.

This paper presents the results of the integration of a high sheet resistance (120 Ω/sq) homogeneous emitter with an industrial feasible process flow on large area p-type CZ-Si PERC solar cells with plated Ni-Si/Cu front contacts. Focus is put on the junction isolation performed by either applying a mask prior to POCl 3 diffusion or by selectively removing the rear side emitter in an inline 1-sided wet-chemical etching tool after diffusion. A metallization sequence [1,2] applying Ni and Cu plating, is performed to contact the moderately doped emitters. The best experimental split in this comparison resulted in excellent average conversion efficiency of 20.2%.

If the world's answer to alternative energy production is to be silicon photovoltaics, the fabricated devices need to be produced with the lowest dollar per watt peak. This may be translated to a high efficiency at competitive costs. An easily implementable approach to increase solar cell efficiency without incurring too much cost is to include thermal oxidation [1,2,3,4]. Thermally grown silicon oxide is well known in the microelectronics industry as one of the best dielectrics to passivate silicon surfaces. This paper will focus on two simultaneous properties related to thermal oxidation. The first is the phosphorus emitter and how it can be significantly altered even at low temperatures (800C). The second is passivation due to the thermal oxidation of both front and rear surfaces. A 60 and an 80 Ω/□ emitter (compatible with silver screen printed contact formation) will be investigated with various oxidation conditions using secondary ions mass spectroscopy (SIMS), scanning spreading resistance (SRP), emitter saturation currents (J oe ) as well as final solar cell devices. We report that increasing oxidation significantly decreases phosphorus surface concentration (N s ) while increasing junction depth. The final cell results show that increasing oxidation increases both open circuit voltage (V oc ) as well as fill factor (FF), however the current density (J sc ) is reduced partly due to front reflection loss. The cells studied in this paper are fabricated on 149cm2, 155µm thin 1.5 ohm.cm p-type Cz-Si wafers that have screen printed Ag front contacts and a thin thermal oxide on both sides with a rear deposited oxide/nitride stack The highest confirmed efficiency of the cells studied is 19.9% with a Voc of 654mV, Jsc of 38.4 mA/cm2 and a fill factor of 79.3%.

Traditional POCl3 diffusion is performed in large diffusion furnaces heated to ~850 C and takes an hour long. This may be replaced by an implant and subsequent 90-s rapid thermal annealing step (in a firing furnace) for the fabrication of p-type passivated emitter rear contacted silicon solar cells. Implantation has long been deemed a technology too expensive for fabrication of silicon solar cells, but if coupled with innovative process flows as that which is mentioned in this paper, implantation has a fighting chance. An SiOx/SiNy rear side passivated p-type wafer is implanted at the front with phosphorus. The implantation creates an inactive amorphous layer and a region of silicon full of interstitials and vacancies. The front side is then passivated using a plasma-enhanced chemical vapor deposited SiNxHy. The wafer is placed in a firing furnace to achieve dopant activation. The hydrogen-rich silicon nitride releases hydrogen that is diffused into the Si, the defect rich amorphous front side is immediately passivated by the readily available hydrogen; all the while, the amorphous silicon recrystallizes and dopants become electrically active. It is shown in this paper that the combination of this particular process flow leads to an efficient Si solar cell. Cell results on 160-µm thick, 148.25-cm2 Cz Si wafers with the use of the proposed traditional diffusion-free process flow are up to 18.8% with a Voc of 638 mV, Jsc of 38.5 mA/cm2, and a fill factor of 76.6%. Copyright © 2012 John Wiley & Sons, Ltd.

Interdigitated back-contact solar cells for high efficiency applications are usually manufactured in R&D laboratories by multiple subsequent lithography steps. Here the patterning by litho-free steps is proposed and implemented. The current status of the small area (2×2cm2 and 4×4cm2) n-type IBC solar cells integration flow is presented with exclusively laser-based patterning scheme: emitter, metal point contacts and electrode separation. Electrode separation is performed in 2 typical configurations: above emitter region or BSF region, where the 2nd location proofs to be beneficial. The best Suns V oc reaches up to 647 mV and p-FF up to 83%.

Interdigitated back contacted cells (IBC) constitute an excellent option for the achievement of high-efficiency on silicon material [1,2]. The effective implementation of an electrical field on the front side, also called Front Surface Field (FSF) is beneficial for this cell concept. It contributes to the reduction of the recombination and the enhancement of the lateral conductivity, improving the cell efficiency [3]. The ideal FSF would push the minority carriers away, while restricting the Auger-recombination-active region to a minimal depth. In addition, too high doping leads to increased absorption in a highly-recombinative region, due to bandgap narrowing. Therefore, a trade-off should be achieved in an n-type IBC solar cell by the combination of a highly-doped n+ surface with a shallow doping profile.

Background: Indirect alternatives to sequencing as a method for mutation scanning are of interest to diagnostic laboratories because they have the potential for considerable savings in both time and costs. Ideally, such methods should be simple, rapid, and highly sensitive, and they should be validated formally to a very high standard. Currently, most reported methods lack one or more of these characteristics. We describe the optimization and validation of conformation-sensitive capillary electrophoresis (CSCE) for diagnostic mutation scanning. Methods: We initially optimized the performance of CSCE with a systematic panel of plasmid-based controls. We then compared manual analysis by visual inspection with automated analysis by BioNumerics software (Applied Maths) in a blinded interlaboratory validation with 402 BRCA1 (breast cancer 1, early onset) and BRCA2 (breast cancer 1, early onset) variants previously characterized by Sanger sequencing. Results: With automated analysis, we demonstrated a sensitivity of >99% (95% CI), which is indistinguishable from the sensitivity for conventional sequencing by capillary electrophoresis. The 95% CI for specificity was 90%–93%; thus, CSCE greatly reduces the number of fragments that need to be sequenced to fully characterize variants. By manual analysis, the 95% CIs for sensitivity and specificity were 98.3%–99.4% and 93.1%–95.5%, respectively. Conclusions: CSCE is amenable to a high degree of automation, and analyses can be multiplexed to increase both capacity and throughput. We conclude that once it is optimized, CSCE combined with analysis with BioNumerics software is a highly sensitive and cost-effective mutation-scanning technique suitable for routine genetic diagnostic analysis of heterozygous nucleotide substitutions, small insertions, and deletions.

Background Survivin is a unique member of the inhibitor of apoptosis protein (IAP) family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated. Results To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ) and the subgranular zone (SGZ). We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (Survivin Camcre ) with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. Survivin Camcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning. Conclusions The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.

A homogeneous emitter designed for a high efficiency Si solar cell needs to fulfill specific requirements: (1) a low surface concentration of dopants and (2) a good contact resistance. The emitter formation is studied in detail for an optimized POCl 3 diffusion scheme and for plasma doping.

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 net- work (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 manu- facturer of the LightScanner TM (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, 899-909, 2009. & 2009 Wiley-Liss, Inc.

Since the introduction of megasonic cleaning in semiconductor industry a debate has been going on about which physical mechanism is responsible for the removal of particles. Because of the high frequency range it was believed that acoustic cavitation could not occur and cleaning was attributed to phenomena like Eckart and Schlichting streaming or pressure build-up on particles [1,2]. Recently it was shown however, that the removal of nanoparticles is closely related to the presence of acoustic cavitation in megasonic cleaning systems [3]. The dependence of particle removal efficiency on the concentration of dissolved gas and the presence of sonoluminescence are clear (but indirect) indications that the underlying mechanism is related to bubble dynamics. As the requirements for cleaning in semiconductor processing are ever more stringent, it becomes necessary to obtain a thorough understanding of the physical behavior of acoustically driven microbubbles in contact with a solid wall. In particular, the forces exerted thereby which might clean or damage a substrate are of interest. Here, a step in this direction is taken by visualization of both the removal of nanoparticles and the sub-microsecond timescale dynamics of the cavitation bubbles responsible thereof.

A key challenge in the engineering of Ge MOSFETs is to develop a proper Ge surface passivation technique prior to high-κ dielectric deposition to obtain low interface state density and high carrier mobility. A review on some possible treatments to passivate the Ge surface is discussed. Another important aspect is the activation of p- and n-type dopants to form the active areas in devices. Finally, Ge deep submicron n- and p-FET devices fabricated with this technique on germanium-on-insulator substrates, yield promising device characteristics, showing the feasibility of these substrates.