Digital inverse patterning solutions for fabrication of high-fidelity microstructures in spatial light modulator (SLM)-based projection lithography.

Digital mask projection lithography (DMPL) technology is gaining significant attention due to its characteristics of free-mask, flexibility, and low cost. However, when dealing with target layouts featuring sizes smaller than the wavelength scale, accurately producing resist patterns that closely match the target layout using conventional methods to design the modulation coefficients of digital masks produced by spatial light modulators (SLM) becomes challenging. Here, we present digital inversion lithography technology (DILT), which offers what we believe to be a novel approach to reverse engineer the modulation coefficients of digital masks. In the case of binary amplitude modulation, DILT achieves a remarkable reduction in pattern errors (PE), reaching the original 0.26. At the same time, in the case of the gray amplitude modulation, the PE can be reduced to the original 0.05, which greatly improves the high-fidelity transfer of the target layout. This significant improvement enhances the accuracy of target design transfer. By leveraging the capabilities of DILT, DMPL can now attain higher precision and reliability, paving the way for more advanced applications in the field of micro-nano device manufacturing.

Optical proximity correction of hot-spot patterns with subwavelength size in DMD maskless projection lithography.

When the critical dimension (CD) of resist patterns nears the resolution limit of the digital micromirror device (DMD) maskless projection lithography (DMD-MPL), significant distortion can emerge in the silicon wafer due to the optical proximity effect (OPE). The significant distortion (breakpoints, line-end scaling, corner rounding, etc.) between resist patterns and target patterns results in reduced lithographic quality. To address this issue, we have proposed a pixel-based optical proximity correction (PB-OPC) method used for the hot-spot patterns with subwavelength sizes specifically designed for DMD-MPL. Employing an end-to-end learning neural network, the PB-OPC algorithm is both straightforward and efficient. A well-trained U-net framework facilitates the mapping from unoptimized masks to optimized masks. Experimental exposure trials have demonstrated that this method not only corrects OPC in general patterns but also effectively rectifies hot-spot patterns. The pattern error (PE) value can be reduced by about 30% in the design layouts. We believe this approach holds the potential to enhance the resolution and fidelity of resist patterns in DMD maskless lithography.

Generating an M2 × N2 spot array with a dual-period hybrid Dammann grating fabricated using maskless projection lithography.

The Dammann grating (DG), which redistributes a collimated laser beam into a spot array with a uniform intensity, is a widely adopted approach for profile measurement. Conventional DGs for dense spot projection are binary phase gratings with precisely designed groove structures, which suffer from low efficiency, poor uniformity, and a hard-to-fabricate fine feature size when utilized for a large field of view (FOV). Here, we propose a new, to the best of our knowledge, hybrid DG architecture consisting of two different grating periods which effectively generates an engineering M2 × N2 spot array with a non-complex structural design. As a proof-of-concept, a dual-period hybrid DG with a two-scale grating period ratio of 11.88 µm/95.04 µm (∼1/8) is designed and fabricated as a means to generate a dense 72 × 72 diffraction spot array with a FOV of 17° × 17°. In addition, the DG exhibits superior performance, with a high efficiency (>60%) and a low non-uniformity (<18%) at a wavelength of 532 nm. This kind of hybrid DG constructed from photoresist patterns with a minimum feature size of ∼1.2 µm can be perfectly fabricated by maskless projection lithography for large-scale and low-cost production. The proposed dual-period hybrid DG can pave the way for depth-perception-related applications such as face unlocking and motion sensing.

Treatment outcomes of mucosal melanoma of the head and neck: Analysis of 190 cases from a single institution.

Objectives: To analyze the treatment outcomes and prognostic factors of mucosal melanoma of the head and neck (MMHN) from a single institution. Methods: From December 1989 to November 2018, 190 patients diagnosed with MMHN were included. Survival analysis was performed using the Kaplan-Meier method for univariate analysis with a log-rank test for significance and Cox regression for multivariate analysis. Results: With a median follow-up time of 43.5 months, 126 (68.5%) patients died. The median DSS was 35 months. The 3- and 5-year disease-specific survival (DSS) rates were 48.1% and 33.7%, respectively. The median overall survival (OS) was 34 months. The 3- and 5-year OS rates were 47.0% and 32.9%, respectively. In univariate analysis, the T3 stage, received surgery, R0 resection, and combined therapy (surgery+biotherapy/biochemotherapy) were significantly associated with better survival. Multivariable Cox regression analysis revealed that the T4 stage (HR = 1.692; 95% CI, 1.175-2.438; p = .005) and the N1 stage (HR = 1.600; 95% CI, 1.023-2.504; p = .039) were strong prognostic factors for poor survival, and that combined therapy (surgery+biotherapy/biochemotherapy) was a strong prognostic factor for better survival outcome (HR = 0.563; 95% CI, 0.354-0.896; p = .015). Conclusion: The prognosis of MMHN remains poor. Systemic treatment is warranted to reduce MMHN progression. Surgery combined with biotherapy may improve survival.

Label-free neural networks-based inverse lithography technology.

Neural network-based inverse lithography technology (NNILT) has been used to improve the computational efficiency of large-scale mask optimization for advanced photolithography. NNILT is now mostly based on labels, and its performance is affected by the quality of labels. It is difficult for NNILT to achieve high performance and extrapolation ability for mask optimization without using labels. Here, we propose a label-free NNILT (LF-NNILT), which is implemented completely without labels and greatly improves the printability of the target layouts and the manufacturability of the synthesized masks compared to the traditional ILT. More importantly, the optimization speed of LF-NNILT is two orders of magnitude faster than the traditional ILT. Furthermore, LF-NNILT is simpler to implement and can achieve better solvers to support the development of advanced lithography.

Maximizing energy utilization in DMD-based projection lithography.

In digital micromirror device (DMD)-based projection photolithography, the throughput largely depends on the effectiveness of the laser energy utilization, which is directly correlated to the diffraction efficiency of DMD. Here, to optimize the DMD diffraction efficiency and thus the laser energy utilization, we calculate the diffraction efficiencies Ediffraction of DMD with various pitch sizes at wavelengths ranging from 200 nm to 800 nm, using the two-dimensional blazed grating diffraction theory. Specifically, the light incident angle is optimized for 343 nm laser and 7.56 µm pitch-size DMD, and the maximum single-order diffraction efficiency Ediffraction is increased from 40% to 96%. Experimentally, we use the effective energy utilization ηeff = Ediffraction,(m,n)/Σ[Ediffraction,(m,n)] at the entrance pupil plane of the objective to verify the effectiveness of the optimized illumination angle in a lithography illumination system with parallel beams of two wavelengths (343 nm and 515 nm). The ηeff of a "blaze" order at a 34° angle of incidence can be optimized up to 88%. The experimental results are consistent with the tendency of the calculated results, indicating that this optimization model can be used to improve the energy utilization of projection lithography with the arbitrarily designable wavelengths and the DMD's pitch size.

[Mechano-growth factor regulated cyclic stretch-induced osteogenic differentiation and MMP-1, MMP-2 expression in human periodontal ligament cells by activating the MEK/ERK1/2 pathway].

PURPOSE: To explore the role and mechanism of mechano-growth factor (MGF) in cyclic stretch (CS)-induced osteogenic differentiation and MMP-1, MMP-2 expression in human periodontal ligament cells (hPDLCs). METHODS: HPDLCs were isolated and transfected with si-MGF, or stimulated with MGF or MEK/ERK pathway inhibitor U0126. Cells were cultured in Flexercell system with 10% elongation at 0.1 Hz. An alkaline phosphatase (ALP) kit was used to detect ALP activity. QRT-PCR assay was performed to determine the transcript levels of MGF and osteogenic genes, including ALP, runt-related transcription factor 2 (Runx2) and osteopontin (OPN). Western bot was used to evaluate the effect on MEK/EKR1/2 signaling. Statistical analysis was performed using SPSS 19.0 software package. RESULTS: CS induced the expression of MGF in hPDLCs in a time-dependent manner (P＜0.05). In contrast to the control group, transfection with si-MGF inhibited the expression of MGF in hPDLCs (P＜0.05). Moreover, cessation of MGF dramatically suppressed ALP activity (P＜0.05) and the expression of osteogenic gene ALP, Runx2 and OPN (P＜0.05) in hPDLCs. Furthermore, down-regulation of MGF restrained the expression of MMP-1 and MMP-2, in contrast to CS group (P＜0.05). Conversely, stimulation with MGF further enhanced the effects of CS on osteogenic differentiation of hPDLCs and MMP-1, MMP-2 expression (P＜0.05). Additionally, MGC silencing abrogated CS-induced expression of p-ERK (P＜0.05), which was further enhanced following MGF treatment (P＜0.05). Simultaneously, precondition with U0126 antagonized MGF-enhanced effects on CS-triggered osteogenic differentiation and MMP-1, MMP-2 expression (P＜0.05). CONCLUSIONS: Mechano-growth factor regulates cyclic stretch-induced osteogenic differentiation and MMP-1, MMP-2 expression in human periodontal ligament cells by activating MEK/ERK1/2 signaling pathway.

Adaption of microbial community during the start-up stage of a thermophilic anaerobic digester treating food waste.

A successful start-up enables acceleration of anaerobic digestion (AD) into steady state. The microbial community influences the AD performance during the start-up. To investigate how microbial communities changed during the start-up, microbial dynamics was analyzed via high-throughput sequencing in this study. The results confirmed that the AD was started up within 25 d. Thermophilic methanogens and bacterial members functioning in hydrolysis, acidogenesis, and syntrophic oxidation became predominant during the start-up stage, reflecting a quick adaption of microorganisms to operating conditions. Such predominance also indicated the great contribution of these members to the fast start-up of AD. Redundancy analysis confirmed that the bacterial abundance significantly correlated with AD conditions. The stable ratio of hydrogenotrophic methanogens to aceticlastic methanogens is also important to maintain the stability of the AD process. This work will be helpful to understand the contribution of microbial community to the start-up of AD.

Optimization modeling of single-chain antibody against hepatoma based on similarity algorithm.

The purposes was to establish optimal modeling of single-chain antibody molecules based on similarity algorithm and seek the connecting peptides that had the minimal effect on the structure and bioactivity of the variable region of heavy chain (VH) and that of light chain (VL) in a single-chain antibody against liver cancer. After the Linker with different lengths (n=0~7) had been added into single chain fragment variable (ScFv), modeling of the overall sequences of VH, VL and ScFv were conducted respectively. Meanwhile, the peptide chain structure of (Gly4Ser)n was adopted for the connecting peptide. Then the spatial spherical shell layer alignment algorithm based on spherical polar coordinates was utilized for comparing the structural similarity of VH and VL before and after adding connecting peptide. Equally, in order to determine the stability of VH and VL, MATLAB was applied for analysis of the fore and aft distances and the diffusion radius. Indirect ELISA method was used to detect single-chain antibody immunological activity of Linker with different lengths. The MTT assay was utilized for the examination of the inhibition rate of single-chain antibody with different lengths of Linker to liver cancer cell. When n=4, the structural similarity between VH together with VL and their original ones was the highest. When n=3, the influence of connecting peptide on the stability of VH and VL was minimum. When n>3, the fore and aft distances changed little due to the increase and fold of the length of peptide chain. The results of ELISA detection showed that when n=4, affinity of single chain antibody to liver cancer cells was much higher. The MTT test also indicated that when n=4, the inhibition rate of the connecting peptide on hepatoma carcinoma cell reached the highest, and that came second when n=3. When n=4, the structural stability and biological functions of anti-hepatoma single-chain antibody were both favorable. This study has provided a basis for the design and construction of single-chain antibody.

Quercetin reversed lipopolysaccharide-induced inhibition of osteoblast differentiation through the mitogen­activated protein kinase pathway in MC3T3-E1 cells.

Quercetin, a flavonoid found in onions and other vegetables, has potential inhibitory effects on bone resorption in vivo and in vitro. In our previous study it was identified that quercetin triggered the apoptosis of lipopolysaccharide (LPS)­induced osteoclasts and inhibited bone resorption. Currently, little information is available detailing the effect of quercetin on osteoblast differentiation and bone formation in bacteria­induced inflammatory diseases. The present study aimed to investigate the effect of quercetin on osteoblast differentiation in MC3T3­E1 osteoblasts stimulated with LPS. LPS significantly downregulated the mRNA expression of osteoblast­related genes in the MC3T3­E1 cells. By contrast, quercetin significantly restored the LPS­suppressed mRNA expression of osteoblast­related genes in a dose­dependent manner. Quercetin also restored the protein expression of Osterix in MC3T3­E1 cells suppressed by LPS. Furthermore, quercetin selectively triggered the activation of the mitogen­activated protein kinase (MAPK) pathway by enhancing the expression of extracellular signal-regulated kinase and reducing the expression of c­Jun N­terminal kinase. These data suggest that quercetin reversed the inhibition of osteoblast differentiation induced by LPS through MAPK signaling. These findings suggest that quercetin may be of potential use as a therapeutic agent to restore osteoblast function in bacteria­induced bone diseases.

[Photocatalytic reductive degradation of direct red 4BE by phosphotungstic acid].

The photoreductive degradation of Azo-dye Direct Red 4BE (4BE) in aqueous solution was studied in a batch photoreactor, with phosphatotungstic acid (H3PW12O40, PW12) as the homogeneous catalyst and isopropanol as the electron donor. The parameters such as concentrations of PW12, isopropanol and 4BE, ionic strength were carefully evaluated. The results showed that 4BE could be reductively decolorized by heteropoly blue, which was produced by phosphatotungstic acid in the presence of isopropanol under UV irradiation. The decolorization rate reached 90.39% within 50 min at a pH value of 2.0, a 4BE initial concentration of 50 mg x L(-1), a PW12 and IS concentration of 600 mg x L(-1) and 0.13 mol x L(-), respectively. The decolonization rate of 4BE increased with the increase of PW12 and isopropanol concentrations until reaching a constant value. However, the first-order rate constants k for the degradation of 4BE decreased with the increase of the 4BE initial concentration. Mutual effects were found between the concentration of isopropanol and PW12 on the photocatalytic degradation of 4BE. Moreover, the concentration of salt showed a negative effect on the photoreductive degradation of 4BE. It was assumed that the charge-transfer occurred within the complex formed by heteropoly bule and 4BE, which led to the reduction of 4BE and regeneration of heteropoly bule. This study indicates that PW12/isopropanol/UV system could be used for the reductive degradation of azo dyes.

[Adsorption of Acid Red 3R on chitosan and its enhancement by Cu2+ co-sorption].

Chitosan was used for the removal of Acid Red 3R from aqueous solutions. Batch adsorption studies were carried out to investigate adsorption kinetics and thermodynamics and the effect of coexisting pH, NaCl, and Cu2+ on adsorption. Experimental data were exploited for kinetic and thermodynamic evaluations related to the adsorption processes. The kinetic data correlated well with the pseudo-second-order kinetic model, indicating the chemical sorption via complex formation/ion exchange. The equilibrium data were well fitted by three isotherm models, namely, Langmuir, Freundlich and Dubinin-Radushkevich (D-R) equations. Moreover, adsorption of Acid Red 3R onto the chitosan was found to be strongly depending on solution temperature and pH. However, the addition of sodium chloride was found to have little effect on the adsorption process. Thermodynamic studies revealed the adsorption process was exothermic in natural. The adsorption free energies derived from D-R equation were in range of 9.5-10.7 kJ x mol(-1), implying that the sorption process is a chemical ion-exchange mechanism. In addition, adsorption capacity of chitosan to Acid Red 3R was found to be greatly enhanced in the presence of Cu2+. A model correlating the concentration of Cu2+ with the enhanced amount of dye adsorbed was established.