The next generation of this technology (using a high-numerical aperture (NA) at 0.55 compared to the present at 0.33) is also currently being prepared and is scheduled to be production ready within the next few years. However, it is well known that the application of higher NA will lead to smaller depth of focus (DOF). The DOF with NA 0.55 systems will reduce to 1/3 of the value that we have in current 0.33 NA systems, i.e. if DOF at NA 0.33 is 100nm then at NA 0.55, DOF will be around 30 to 40nm. At these exposure conditions, wafer surface distortions as an effect of backside defects will become significant concern. In this study, the wafer backside at exactly the same locations detected as where these abnormal CD's were detected on wafer frontside. And the evidence was shown that the backside defects affected to frontside pattern deformation. Furthermore, it was found that an effective backside cleaning process can mitigate pattern defocus caused by these wafer backside particles.
Control of wafer backside defectivity is a challenge during the chip manufacturing process and has been extensively investigated throughout the past decade, especially on immersion lithography systems. As technology nodes continue to scale down and we approach the high NA EUV lithography era, backside contamination is becoming a critical problem. High NA EUV exposure systems have a smaller depth of focus compared to low NA EUV systems. The presence of backside wafer defects can easily lead to focus loss or on-product overlay errors leading to pattern failures. To anticipate the upcoming challenges, SCREEN has developed a sophisticated track-integrated backside cleaning (BSC) module on the DT-3000 system. This enables an advanced post-coating BSC solution directly before exposure. Together ASML, imec and SCREEN, investigated the potential of this unique BSC process to extend the lithographic performance of EUV material stacks, by correlating backside contamination with frontside patterning performance and the minimization of scanner focus spots. With this approach, we try to identify and characterize potential backside defect killers that could cause not only yield loss, but also physical deterioration of the scanner wafer table (WT) and its lifetime.
Understanding longitudinal changes of tumor-immune microenvironment during chemo/targeted therapies contributes to the development of optimized combinations of immunotherapy with chemotherapy and targeted therapy for patients with head and neck squamous cell carcinoma (HNSCC). We previously reported a chromogenic sequential immunohistochemical (IHC) platform enabling quantitative and spatial assessment of 29+ biomarkers in a single tissue section (Tsujikawa T et al. Cell Reports 2017, Banik G et al. Methods Enzymology 2020). Using this platform, densities, phenotypes, and distributions of tumor and immune cells were evaluated, comparing baseline and post-treatment specimens from the same individual treated by paclitaxel, carboplatin, and cetuximab (PCE) for advanced HNSCC (N = 30). Immune cell density analyses based on CD8+ T cells, helper T cells, regulatory T cells, B cells, natural killer cells, macrophages, dendritic cells, mast cells, granulocytes revealed the presence of differential immune cell compositions, where immune profiles were divided into hypo-, lymphoid-, and myeloid-inflamed groups according to the same criteria as in our previous report (Tsujikawa et al. Cell Reports 2017). Lymphoid and hypo-inflamed groups exhibited significant tumor volume reduction, increased CD45+ immune cell densities and elevated combined positive scores of PD-L1 at the post-treatment status, suggesting the potential involvement of immunogenic mechanisms related to therapeutic response. On the other hand, the myeloid group exhibited no significant tumor volume reduction, together with higher expression of HIF1α and ZEB2 on tumor cells which are potentially associated with hypoxia and epithelial-mesenchymal transition. In conclusion, longitudinal tissue-based monitoring revealed the presence of differential tumor-immune complexity profiles related to therapeutic efficacy and resistance. Hypo-inflamed profiles might require upfront chemo/targeted therapy before immunotherapy, and myeloid-inflamed profiles might require myeloid cell-targeted therapies, mandating the establishment of rapid clinical assessment of tumor-immune microenvironment. Citation Format: Alisa Kimura, Takahiro Tsujikawa, Junichi Mitsuda, Aya Miyagawa-Hayashino, Hiroki Morimoto, Sumiyo Saburi, Kanako Yoshimura, Gaku Ohmura, Sigeyuki Mukudai, Hikaru Nagao, Yoichiro Sugiyama, Hiroshi Ogi, Saya Shibata, Eiichi Konishi, Kyoko Itoh, Shigeru Hirano. Tumor-immune microenvironmental profiling during chemo- and targeted therapy for head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5172.
