Akito Kawai

Ultra thinning 300-mm wafer down to 7-µm for 3D wafer Integration on 45-nm node CMOS using strained silicon and Cu/Low-k interconnects

High performance 45-nm Node and its 3D integration employed aggressively thinned down to 7- µm of 300-mm wafer for the Wafer-on-a-Wafer (WOW) application has been succeeded for the first time. The impact of ultra thin wafer on strained transistors and Cu/low-k multilevel interconnects is described. Properties examined include Kelvin and stack chain resistances of Cu interconnects as well as Ion-Ioff, threshold voltage shift, and junction leakage of transistors. It was found that the electrical properties were not affected by bonding, thinning and debonding process indicating good feasibility of 3D stacking integration to the strain and low-k technology.

A novel heterotetrameric structure of the crenarchaeal PCNA2-PCNA3 complex

Proliferating cell nuclear antigen (PCNA) is a key protein that orchestrates the arrangement of DNA-processing proteins on DNA during DNA metabolism. In crenarchaea, PCNA forms a heterotrimer (PCNA123) consisting of PCNA1, PCNA2, and PCNA3, while in most eukaryotes and many archaea PCNAs form a homotrimer. Interestingly, unique oligomeric PCNAs from Sulfolobus tokodaii were reported in which PCNA2 and PCNA3 form a heterotrimer without PCNA1. In this paper, we describe the crystal structure of the stoPCNA2-stoPCNA3 complex. While most DNA sliding clamps form ring-shaped structures, our crystal structure showed an elliptic ring-like heterotetrameric complex, differing from a previous reports. Furthermore, we investigated the composition and the dimension of the stoPCNA2-stoPCNA3 complex in the solution using gel-filtration column chromatography and small-angle X-ray scattering analyses, respectively. These results indicate that stoPCNA2 and stoPCNA3 form the heterotetramer in solution. Based on our heterotetrameric structure, we propose a possible biological role for the heterotetrameric complex as a Holliday junction clamp.

A robust wafer thinning down to 2.6-μm for bumpless interconnects and DRAM WOW applications

An ultra-thinning down to 2.6-μm with and without Cu contamination at 1013 atoms/cm2 using 300-mm wafer proven by 2Gb DRAM has been developed for the first time. The impact of Si thickness and Cu contamination at wafer backside for DRAM yield including retention characteristics is described. Thickness uniformity for all wafers after thinning was below 2-μm within 300-mm wafer. A degradation in terms of retention characteristics occurred after thinning down to 2.6-μm while no degradation after thinning down to 5.6-μm for both wafer and package level test were found.

Purification, crystallization and preliminary X-ray analysis of the PCNA2–PCNA3 complex from Sulfolobus tokodaii strain 7

Crenarchaeal PCNA is known to consist of three subunits (PCNA1, PCNA2 and PCNA3) that form a heterotrimer (PCNA123). Recently, another heterotrimeric PCNA composed of only PCNA2 and PCNA3 was identified in Sulfolobus tokodaii strain 7 (stoPCNAs). In this study, the purified stoPCNA2-stoPCNA3 complex was crystallized by hanging-drop vapour diffusion. The crystals obtained belonged to the orthorhombic space groups I222 and P2(1)2(1)2, with unit-cell parameters a = 91.1, b = 111.8, c = 170.9 A and a = 91.1, b = 160.6, c = 116.6 A, respectively. X-ray diffraction data sets were collected to 2.90 A resolution for the I222 crystals and to 2.80 A resolution for the P2(1)2(1)2 crystals.

Crystallographic analysis of the ternary complex of octanoate and N-acetyl-l-methionine with human serum albumin reveals the mode of their stabilizing interactions

During pasteurization and storage of albumin products, Sodium octanoate (Oct) and N-acethyl-l-tryptophan (N-AcTrp) are used as the thermal stabilizer and the antioxidant for human serum albumin (HSA), respectively. We recently reported that N-acethyl-l-methionine (N-AcMet) is an antioxidant for HSA, which is superior to N-AcTrp when it is especially exposed to light during storage. The objective of the present study is to clarify the molecular mechanism responsible for the HSA protective effect of Oct and N-AcMet based on their ternary complex structure. Crystal structure of the HSA-Oct-N-AcMet complex showed that one N-AcMet molecule is bound to the entrance of drug site 1 of HSA, and its side chain, which is susceptible to the oxidation, is exposed to the solvent. At the same time, two Oct binding sites are observed in drug sites 1 and 2 of HSA, respectively, and each Oct molecule occupies the hydrophobic cavity in them. These results indicate the molecular mechanism responsible for the HSA stabilization by these small molecules as follows. N-AcMet seals the entrance of drug site 1 while it acts as an antioxidant for HSA. Oct is chiefly bound to drug site 2 of HSA and it increases the thermal stability of HSA because of the occupying the largest intra-cavity of sub-domain IIIA in HSA. These findings suggest that N-AcMet acts positively as useful stabilizer for albumin formulated products such as functionalized HSA and HSA fusion proteins.

Purification, crystallization and preliminary X-ray analysis of uracil-DNA glycosylase from Sulfolobus tokodaii strain 7

Uracil-DNA glycosylase (UDG) specifically removes uracil from DNA by catalyzing hydrolysis of the N-glycosidic bond, thereby initiating the base-excision repair pathway. Although a number of UDG structures have been determined, the structure of archaeal UDG remains unknown. In this study, a deletion mutant of UDG isolated from Sulfolobus tokodaii strain 7 (stoUDGΔ) and stoUDGΔ complexed with uracil were crystallized and analyzed by X-ray crystallography. The crystals were found to belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 52.2, b = 52.3, c = 74.7 Å and a = 52.1, b = 52.2, c = 74.1 Å for apo stoUDGΔ and stoUDGΔ complexed with uracil, respectively.

Species Differences in the Binding of Sodium 4-Phenylbutyrate to Serum Albumin

Sodium 4-phenylbutyrate (PB) is clinically used as a drug for treating urea cycle disorders. Recent research has shown that PB also has other pharmacologic activities, suggesting that it has the potential for use as a drug for treating other disorders. In the process of drug development, preclinical testing using experimental animals is necessary to verify the efficacy and safety of PB. Although the binding of PB to human albumin has been studied, our knowledge of its binding to albumin from the other animal species is extremely limited. To address this issue, we characterized the binding of PB to albumin from several species (human, bovine, rabbit, and rat). The results indicated that PB interacts with 1 high-affinity site of albumin from these species, which corresponds to site II of human albumin. The affinities of PB to human and bovine albumins were higher than those to rabbit and rat albumin, and that to rabbit albumin was the lowest. Binding and molecular docking studies using structurally related compounds of PB suggested that species differences in the affinity are attributed to differences in the structural feature of the PB-binding sites on albumins (e.g., charge distribution, hydrophobicity, shape, or size).

Electrical characteristics of bumpless interconnects for through silicon via (TSV) and Wafer-On-Wafer (WOW) integration

This paper describes electrical characteristics of bumpless and dual-damascene TSV interconnects for three-dimensional integration (3DI) using Wafer-on-Wafer (WOW) technology. Process optimization counter to integration issues of TSV formation process is demonstrated using test vehicle fabricated with 300-mm wafer and characterized by chain resistance and leakage current in the wafer level.

Influence of wafer thinning process on backside damage in 3D integration

Ultra-thinning less than 10 microns of Si wafer is expected to realize small TSV feature which provides low aspect ratio and coupling capacitance. However, a detail of residual surface damage during thinning is unrevealed. In this paper, subsurface damage following wafer thinning from the back of 300 mm wafers using three different types of thinning process was investigated by means of Raman spectroscopy, XTEM, and Positron annihilation analysis, respectively. A coarse grinding generates significant rough subsurface ranged several micron and damage layer including amorphous and plastic-deformed Si along grinding topography. Fine grinding, second step of thinning, reduced those surface roughness and almost removed after thinning at least removal of 50 microns. However, plastic-deformed subsurface layer with a thickness of 100 to 200 nm are still remained which leaves an inside elastic stress layer ranging up to about 10 microns in depth. Chemical-Mechanical Polishing (CMP) process as a final step of thinning enables to remove residual damages such as structural defects and lattice strains after 1-5 microns thick polishing while vacancy-type defects only remain.

Crystal structure of family 4 uracil-DNA glycosylase from Sulfolobus tokodaii and a function of tyrosine 170 in DNA binding

Uracil–DNA glycosylases (UDGs) excise uracil from DNA by catalyzing theN‐glycosidic bond hydrolysis. Here we report the first crystal structures of an archaeal UDG (stoUDG). Compared with other UDGs,stoUDG has a different structure of the leucine‐intercalation loop, which is important for DNA binding. ThestoUDG–DNA complex model indicated that Leu169, Tyr170, and Asn171 in the loop are involved in DNA intercalation. Mutational analysis showed that Tyr170 is critical for substrate DNA recognition. These results indicate that Tyr170 occupies the intercalation site formed after the structural change of the leucine‐intercalation loop required for the catalysis.