Robust reference intervals are needed for the interpretation of bone turnover markers in large phase III fracture trials. The objectives of the study were to (1) estimate reference intervals for serum bone alkaline phosphatase (bone ALP), serum procollagen type I N propeptide (PINP), serum b cross-linked C-telopeptides of type I collagen (S-bCTX), and urinary cross-linked N-telopeptides of type I collagen (U-NTX) in healthy young premenopausal women; (2) examine geographical differences on bone turnover markers; and (3) assess factors known to influence bone turnover and test whether these explain any regional differences. We studied 637 eligible women from four countries that participated in the Horizon-PFT study (United Kingdom, France, Belgium, United States). The women were 30-39 yr of age (mean, 34.6 yr), with regular cyclic menses. Subjects completed a medical and lifestyle questionnaire. Two-sided 95% reference intervals were estimated on transformed values and transformed back to the original scale using the proposed methodology of the International Federation of Clinical Chemistry. S-bCTX was significantly higher in France relative to the United Kingdom (p = 0.01), and PINP was higher in France (p < 0.001) and Belgium (p = 0.02) relative to the United Kingdom and significantly higher in France relative to the United States (p < 0.01) by ANOVA. Overall, one could associate low bone turnover markers with nonsmoking, use of a contraceptive pill, exercise, being close to the time of ovulation, and having high 25-hydroxyvitamin D levels. Countries differed by these characteristics, and once allowed for in the statistical model, any country differences were attenuated or removed.

No abstract

The detection of early failures in electromigration (EM) and the complicated statistical nature of this important reliability phenomenon have been difficult issues to treat in the past. A satisfactory experimental approach for the detection and the statistical analysis of early failures has not yet been established. This is mainly due to the rare occurrence of early failures and difficulties in testing of large sample populations. Furthermore, experimental data on the EM behavior as a function of varying number of failure links are scarce. In this study, a technique utilizing large interconnect arrays in conjunction with the well-known Wheatstone Bridge is presented. Three types of structures with a varying number of Ti/TiN/Al(Cu)/TiN-based interconnects were used, starting from a small unit of five lines in parallel. A serial arrangement of this unit enabled testing of interconnect arrays encompassing 480 possible failure links. In addition, a Wheatstone Bridge-type wiring using four large arrays in each device enabled simultaneous testing of 1920 interconnects. In conjunction with a statistical deconvolution to the single interconnect level, the results indicate that the electromigration failure mechanism studied here follows perfect lognormal behavior down to the four sigma level. The statistical deconvolution procedure is described in detail. Over a temperature range from 155 to 200 °C, a total of more than 75 000 interconnects were tested. None of the samples have shown an indication of early, or alternate, failure mechanisms. The activation energy of the EM mechanism studied here, namely the Cu incubation time, was determined to be Q=1.08±0.05 eV. We surmise that interface diffusion of Cu along the Al(Cu) sidewalls and along the top and bottom refractory layers, coupled with grain boundary diffusion within the interconnects, constitutes the Cu incubation mechanism.

Raman mapping is performed to study the lateral damage in supported monolayer graphene carved by 30keV focused Ga+ beams. The evolution of the lateral damage is tracked based on the profiles of the intensity ratio between the D (1341cm-1) and G (1582cm-1) peaks (ID/IG) of the Raman spectra. The ID/IG profile clearly reveals the transition from stage 2 disorder into stage 1 disorder in graphene along the direction away from the carved area. The critical lateral damage distance spans from <1μm up to more than 30μm in the experiment, depending on the parameters used for carving the graphene. The wide damage in the lateral direction is attributed to the deleterious tail of unfocused ions in the ion beam probe. The study raises the attention on potential sample damage during direct patterning of graphene nanostructures using the focused ion beam technique. Minimizing the total carving time is recommended to mitigate the lateral damage

Over upcoming electronics technology nodes, shrinking feature sizes of on-chip interconnects and correspondingly higher current densities are expected to result in higher temperatures due to self-heating. This study describes a finite element based compact thermal modeling approach to investigate the effects of Joule heating on complex interconnect structures. In this method, interconnect cross section is assumed to be isothermal and conduction along the interconnect is retained. A composite finite element containing both metal and dielectric regions is used to discretize the interconnect stack. The compact approach predicts the maximum temperature rise in the metal to within 5–10% of the detailed numerical computations, while requiring only a fraction of elements. Computational time for the compact model solution is several seconds, versus many hours for the detailed solutions obtained through successive mesh refinement until grid independence is achieved. For a comparable number of elements, the compact model is in general much more accurate than the traditional finite element approach. To validate the simulations, temperature rise in a 500-link two-layer interconnect with a via layer was measured at several current densities. The compact method predicts the temperature rise of the 500-link chain to within 5% of the measurements thereby validating the method. The approach described here could be an efficient technique for full chip Joule heating simulations and for clock signal propagation simulations, which are performed as part of designing next generation chip architectures.

The early failure issue in electromigration (EM) has been an unresolved subject of study over the last several decades. A satisfying experimental approach for the detection and analysis of early failures has not been established yet. In this study, a technique utilizing large interconnect arrays in conjunction with the well-known Wheatstone Bridge is presented. A total of more than 20 000 interconnects were tested. The results indicate that the EM failure mechanism studied here follows lognormal behavior down to the four sigma level.

Electromigration failure statistics and the origin of the log-normal standard deviation for copper interconnects were investigated by analyzing the statistics of electromigration lifetime and void size distributions at various stages during testing. Experiments were performed on 0.18 m wide Cu interconnects with tests terminated after certain amounts of resistance increase, or after a specified test time. The lifetime and void size distributions were found to follow log-normal distribution functions. The sigma values of these distributions decrease with increasing test time. The statistics of resistance-based void size distributions can be simulated by considering geometrical variations of the void shape. In contrast, the characteristics of time-based void size distributions require consideration of kinetic aspects of the electromigration process. The sigma values of lifetime distributions can be adequately simulated by combining the statistics of both types of void size distributions. Thus, a statistical correlation between electromigration lifetimes and void evolution was established. Using simulation to fit the experimental data, the parameters influencing the electromigration lifetime statistics were identified as variations in void sizes, geometrical and experimental factors of the electromigration experiment, and kinetic aspects of the mass transport process, such as differences in interface diffusivity between the lines. The latter is the result of variations in the copper microstructure at the cathode ends of the interconnects.

Electromigration early failure void nucleation and growth phenomena were studied using large-scale, statistical analysis methods. A total of about 496,000 interconnects were tested over a wide current density and temperature range (j = 3.4 to 41.2 µmA/m2, T = 200 to 350°C) to analyze the detailed behavior of the current density exponent n and the activation energy Ea. The results for the critical V1M1 downstream interface indicate a reduction from n = 1.55±0.10 to n = 1.15±0.15 when lowering the temperature towards 200°C for Cu-based interconnects. This suggests that the electromigration downstream early failure mechanism is shifting from a mix of nucleation-controlled (n = 2) and growth-controlled (n = 1) to a fully growth-controlled mode, assisted by the increased thermal stress at lower temperatures (especially at use conditions). For Cu(Mn)-based interconnects, a drop from n = 2.00±0.07 to n = 1.64±0.2 was found, indicating additional effects of a superimposed incuba tion time. Furthermore, at lower current densities, the Ea value seems to drop for both Cu and Cu(Mn) interconnects by a slight, but significant amount of 0.1 - 0.2eV. Implications for extrapolations of accelerated test data to use conditions are discussed. Furthermore, the scaling behavior of the early failure population at the NSD=-3 level (F about 0.1%) was analyzed, spanning 90, 65, 45, 40 and 28 nm technology nodes