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The etiology of primary Sjogren's syndrome (pSS) remains unknown, and there is no complete curative drug. In this study, we treated a mouse model of the submandibular gland (SG) protein-immunized experimental Sjogren's syndrome (ESS) with paeoniflorin-6'-O-benzene sulfonate (termed CP-25) to evaluate the potential therapeutic effects of CP-25. Through in vivo experiments, we found that CP-25 increased saliva flow, alleviated the salivary gland indexes, and improved tissue integrity in the ESS model. The viability of splenocytes and B-lymphocyte migration from spleen were reduced in ESS mice. Furthermore, CP-25 decreased the expression of IgG antibodies, anti-SSA and anti-SSB antibodies and modulated the levels of cytokines in the serum of SS mice. The numbers of total B lymphocytes, plasma cells (PCs), and memory B cells diminished in the salivary gland. Increased expression of the JAK1-STAT1-CXCL13 axis and IFNα was found in human tissue isolated from pSS patients. In vitro, after stimulation with IFNα, the levels of CXCL13 mRNA and CXCL13 in human salivary gland epithelial cells (HSGEC) increased, while CP-25 counteracted the secretion of CXCL13 and downregulated the expression of CXCL13. IFN-α activated the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which was negatively regulated by additional CP-25. As a consequence, B-cell migration was downregulated in coculture with IFN-α-stimulated HSGEC. Taken together, this study demonstrated that the therapeutic effects of CP-25 were associated with the inhibition of the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which impedes the migration of B cells into the salivary gland. We identified the underlying mechanisms of the therapeutic effect of CP-25 and provided an experimental foundation for CP-25 as a potential drug in the treatment of the human autoimmune disorder pSS.

To explore the biomechanical characteristics of 2 posterior bilateral pedicle screw fixation methods using finite element analysis.A normal L3-5 finite element model was established. Based on the verification of its effectiveness, 2 different posterior internal fixation methods were simulated: bilateral pedicle screws (model A) were placed in the L3 and L5 vertebral bodies, and bilateral pedicle screws (model B) were placed in the L3, L4, and L5 vertebral bodies. The stability and stress differences of intervertebral discs, endplates, screws, and rods between models were compared.Compared with the normal model, the maximum stress of the range of motion, intervertebral disc, and endplate of the 2 models decreased significantly. Under the 6 working conditions, the 2 internal fixation methods have similar effects on the stress of the endplate and intervertebral disc, but the maximum stress of the screws and rods of model B is smaller than that of model A.Based on these results, it was found that bilateral pedicle screw fixation in 2 vertebrae L3 and L5 can achieve similar stability as bilateral pedicle screw fixation in 3 vertebrae L3, L4, and L5. However, the maximum stress of the screw and rod in model B is less than that in model A, so this internal fixation method can effectively reduce the risk of fracture. The 3-dimensional finite element model established in this study is in line with the biomechanical characteristics of the spine and can be used for further studies on spinal column biomechanics. This information can serve as a reference for clinicians for surgical selection.

Background Since 2011, Chongqing Blood Center began routine screening of viral nucleic acid using a multiplex assay for simultaneous detection of HBV DNA, HCV RNA and HIV-1 RNA in blood donations. However, this multiplex nucleic acid testing (NAT) screening system introduced an intractable problem of non-discriminated reactive (NDR) donations, which were serologically nonreactive and reactive in multiplex NAT screening, but nonreactive in the following virus-specific discriminatory NAT assays. Some donations were considered to arise from the presence of low-level HBV DNA due to occult hepatitis B infection (OBI). We identified OBI among NDR donations in Chongqing area. In addition, rationality of the current blood screening strategy was evaluated. Methods From August 2017 to July 2018, 190 NDR blood donations were collected from 140577 volunteer blood donors at Chongqing Blood Center. Repeated discriminatory HBV (dHBV) testing, minipools-NAT (MPs-NAT), quantitative viral load determination and complementary serological testing were used to confirm OBI. Results Of 190 NDR donations, sixty-three (33.2%) were identified as OBI, sixty-one (32.1%) were repeatedly reactive in discriminatory HBV assay. Two (1.1%) were positive for HBV DNA in MPX assay on Roche Cobas s201 system. Of these sixty-three OBI donations, only thirteen (20.6%) were positive in Cobas AmpliPrep/TaqMan HBV DNA quantitative assay, which were all less than 20IU/ml. Anti-HBc and anti-HBs were detected in 85.3% and 58.4% of NDR donors, respectively. Anti-HBc and anti-HBs were detected in 96.8% and 47.6% of confirmed OBI donors in NDR group, respectively. Anti-HBc and anti-HBs were detected in 79.5% and 63.8% of unclassified donors in NDR group, respectively. There was no statistical difference in positive rate of anti-HBc between NDR donations and dHBV-initially-reactive donations (85.3% vs 90.0%). The male to female ratio was 2.2 of OBI donors in NDR group. The proportion of repeat-time OBI donors in NDR group was higher than that in dHBV-initially-reactive group (63.5% vs 50.0%). The median age of OBI donors was 45 years in NDR group. Conclusion A complicated OBI confirmatory procedure with labour-intensive and sophisticated equipment was implemented successfully. OBI with extremely low virus concentration is the main reason for discriminatory NAT nonreactive among blood donors in Chongqing area. The current blood screening strategy is a reasonable measure to reduce the risk of transfusion, which is able to maximize blood safety.

1,1,2-trichloroethane (TCA) is a contaminant in many pesticide and chemical fields. This study mainly described the potential effectiveness of the natural attenuation of 1,1,2-TCA in groundwater in a typical pesticide-contaminated field in east China. In this study, six typical 1,1,2-TCA-contaminated sites (MW14, MW21, MW25, MW31, MW36 and MW41) were selected, and the field investigation results indicated that there was an obvious decline in the concentrations of 1,1,2-TCA over time in all selected sites. Furthermore, the attenuation rate of 1,1,2-TCA concentration in sites MW14, MW21, MW25, MW31 and MW41 followed the first-order kinetic equation, and the first-order attenuation rate constants were calculated. The health risks of 1,1,2-TCA and its degradation product dichloroethane (DCA) were assessed and compared in site MW14. The result showed that the health risks of 1,1,2-TCA were much higher than those of DCA, and 1,1,2-TCA was the contamination source in this site. 16S rRNA sequencing was also conducted to investigate the diversity of the bacterial community in 1,1,2-trichloroethane (TCA)-contaminated groundwater, and Geobacter, Thauera, Pseudomonas, Diaphorobacter were the main species in the bacterial community.

The chronic inflammatory autoimmune disease rheumatoid arthritis (RA) is characterized by an infiltration of activated proinflammatory immune cells into the joint that is accompanied by an overproduction of various mediators, leading to destruction of cartilage and bone erosion. Angiotensin II type 2 receptor (AT2R) is involved in antioxidative, anti-inflammatory, and antifibrotic responses. Synovial macrophages (SMs) are a type of tissue macrophages that are derived from bone marrow cells. SMs plays a central role in synovial regional immunization, which is significantly increased in both collagen-induced mice with arthritis mice and RA patients. AT2R activation caused a reversal of the polarization of SMs in the joint from the proinflammatory M1 SM to the tolerogenic, benign M2 SM. In consequence, this switch resulted in an attenuated form of the joint pathology in a rat model of collagen-induced arthritis. These results were mechanistically linked to the observation that GRK2 was translocated into cytoplasm, and ERK1/2 and NF-κB activation were inhibited. These findings open the way to a new therapeutic approach using an activation of AT2R to subvert joint inflammation in RA.

The etiology of primary Sjogren's syndrome (pSS) remains unknown, and there is no ideal drug for the specific treatment of pSS. β-arrestin2 is a key protein that mediates desensitization and internalization of G protein-coupled receptors (GPCRs) and it participates in inflammatory and immune responses that have been found to mediate apoptosis in autoimmune disease. In this study, we established an experimental Sjogren's syndrome (ESS) mouse model to elucidate the molecular mechanisms of β-arrestin2 in pSS. First, excessive activation of β-arrestin2 and GRP78-ATF6-CHOP apoptosis signaling were detected in specimens from pSS patients. In vivo, we found that inhibition of GRP78-ATF6-CHOP apoptosis signaling improved ESS symptoms, and the targeted deletion of β-arrestin2 significantly increased saliva flow, alleviated salivary gland indices, and improved tissue integrity in the ESS model by downregulating GRP78-ATF6-CHOP apoptosis signaling. In vitro, we used IFNα to stimulate human salivary gland epithelial cells (HSGECs), and the results showed that IFNα activated GRP78-ATF6-CHOP apoptosis signaling, decreased cell viability, and induced apoptosis, which were negatively regulated by the ERS inhibitor 4-PBA. In addition, β-arrestin2 depletion downregulated GRP78-ATF6-CHOP apoptosis signaling to alleviate cell apoptosis, and the effect depended on the interaction between GRP78 and β-arrestin2. In summary, our results suggest that excessive activation of GRP78-ATF6-CHOP apoptosis signaling is involved in the pathogenesis of pSS and that β-arrestin2 encourages inflammation-induced epithelial apoptosis through GRP78-ATF6-CHOP apoptosis signaling. This research further clarified the underlying role of β-arrestin2 and provided an experimental foundation for β-arrestin2 depletion in the treatment of the human autoimmune disorder pSS.

Previously an enhanced nitrogen removal process, i.e., intermittent Modified Ludzack-Ettinger (iMLE), was developed by incorporating intermittent aeration into the MLE process. In this research, a field demonstration of iMLE process on enhancing nitrogen removal was conducted in Shenzhen Guangming Wastewater Treatment Plant (WWTP) at a daily treatment capacity of 25,000 m3/d. Results indicated that, when operating the iMLE process with dissolved oxygen (DO) based control mode, its effluent chemical oxygen demand (COD) and ammonia concentrations were consistently less than 30 mg/L and 1.5 mg/L, respectively, similar to the original two-stage Anoxic/Oxic (A/O) process with continuous aeration. Even though the influent had insufficient organic matter (BOD5/TN = 2.5), the effluent TN concentration in the iMLE was still consistently below the new limit of 10 mg-N/L, with an average and removal rate of 6.1 ± 1.0 mg-N/L and 78%, respectively. This performance was similar to that in the two-stage A/O process equipped with step feed and external carbon addition. Without the addition of external carbon in the iMLE process, it saved approximately 0.16 Chinese yuan for one cubic meter of wastewater treated. In addition to eliminating external carbon addition, the iMLE process decreased the air consumption by 20–30%, which would also reduce operation cost. Therefore, the iMLE process operated with appropriate DO control could reduce chemical cost and aeration energy use synergistically, which provides a cost-effective approach for WWTP upgrade.

The etiology of primary Sjögren's syndrome (pSS) remains unknown, and there is no complete curative drug. In this study, we treated a mouse model of the submandibular gland (SG) protein-immunized experimental Sjögren's syndrome (ESS) with paeoniflorin-6'-O-benzene sulfonate (termed CP-25) to evaluate the potential therapeutic effects of CP-25. Through in vivo experiments, we found that CP-25 increased saliva flow, alleviated the salivary gland indexes, and improved tissue integrity in the ESS model. The viability of splenocytes and B-lymphocyte migration from spleen were reduced in ESS mice. Furthermore, CP-25 decreased the expression of IgG antibodies, anti-SSA and anti-SSB antibodies and modulated the levels of cytokines in the serum of SS mice. The numbers of total B lymphocytes, plasma cells (PCs), and memory B cells diminished in the salivary gland. Increased expression of the JAK1-STAT1-CXCL13 axis and IFNα was found in human tissue isolated from pSS patients. In vitro, after stimulation with IFNα, the levels of CXCL13 mRNA and CXCL13 in human salivary gland epithelial cells (HSGEC) increased, while CP-25 counteracted the secretion of CXCL13 and downregulated the expression of CXCL13. IFN-α activated the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which was negatively regulated by additional CP-25. As a consequence, B-cell migration was downregulated in coculture with IFN-α-stimulated HSGEC. Taken together, this study demonstrated that the therapeutic effects of CP-25 were associated with the inhibition of the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which impedes the migration of B cells into the salivary gland. We identified the underlying mechanisms of the therapeutic effect of CP-25 and provided an experimental foundation for CP-25 as a potential drug in the treatment of the human autoimmune disorder pSS.

Primary Sjogren's syndrome (pSS) is an autoimmune disease of unresolved aetiology that affects the exocrine glands. Clinical symptoms frequently also involve skin, liver, kidney and neurovascular components. The pathogenesis of pSS is still unclear but B cell hyperactivity has been identified as a hallmark of pSS. Currently, a curative therapeutic agent is lacking. In this study, we explored whether paeoniflorin-6′-O-benzene (CP-25) exerted therapeutic effects through regulating B lymphocyte migration via CXCR5-GRK2-MAPK mediated signaling pathways in a mouse model of antigen-induced, experimental Sjogren's syndrome (ESS). We found that CP-25 increased the salivary flow and alleviated the histopathology of ESS. Furthermore, CP-25 reduced the viability of B lymphocyte and limited the target organs index. In the peripheral blood and salivary gland of ESS mice, CP-25 down-regulated the proportion of total B cells, CXCR5+ B cells and PDCA1 + CD19- and limited the presence of phosphorylated (p-) p38 and ERK (p-ERK). Besides, CP-25 increased the percentage of memory B cells in the peripheral blood and reduced it in salivary gland. Furthermore, in vitro, CP-25 down-regulated p-p38, p-ERK, CXCR5 and membrane GRK2, and increased cytoplasm GRK2 in Maver-1 cells, a mantle cell lymphoma cell line, causing a lower migration ability of Maver-1 cells. Thus, we define CP-25 as a novel compound that is a potent therapeutic agent for pSS which modulates B lymphocyte subsets and impacts the migration of B lymphocytes through regulating the CXCR5-GRK2-ERK/p38 signaling pathway.

We propose a cavity QED system with two-photon Doppler-free configuration for weak magnetic field detection with high sensitivity at room temperature based on cavity electromagnetically induced transparency. Owing to the destructive interference induced by the control and driving fields, two transparency channels are opened. The Faraday rotation within two transparency channels can be used to detect weak magnetic field with high sensitivity at room temperature. The sensitivity with single photon and multiphoton probe inputs is analyzed. With single photon measurement, our numerical calculations demonstrate that the sensitivity with 3.8 nT/ Hz and 6.4 nT/ Hz could be achieved. When we measure the magnetic field with multiphoton input, the sensitivity can be improved to 7.7 fT/ Hz and 25.6 fT/ Hz under the realistic experimental conditions.

Based on the quenching of the fluorescence intensity of thioglycolic acid (TGA)-capped core-shell CdTe/ZnS nanoparticles (NPs) by vanillin, a novel, simple and rapid method for the determination of vanillin was proposed. In aqueous medium, the functionalized core-shell CdTe/ZnS NPs were successfully synthesized with TGA as the capping ligand. TGA-capped core-shell CdTe/ZnS NPs were characterized by using X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Factors affecting the vanillin detection were investigated, and the optimum conditions were also determined. Under the optimum conditions, the relative fluorescence intensity of CdTe/ZnS NPs was linearly proportional to vanillin over a concentration range from 9.4 × 10(-7) to 5.2 × 10(-4) M with a correlation coefficient of 0.998 and a detection limit of 2.6 × 10(-7) M. The proposed method was also employed to detect trace vanillin in cookies with satisfactory results.

In the present study, a novel and sensitive fluorescence probe method has been established for the determination of luteolin (LTL) based on the fluorescence quenching effect of LTL on glutathione (GSH)-capped Mn-doped CdTe quantum dots (QDs). GSH-capped Mn-doped CdTe QDs with a diameter of 6–8 nm were synthesized via a facile and inexpensive method in an aqueous system. The fluorescence of doped CdTe QDs at 541 nm was quenched in the presence of LTL with an excitation wavelength at 351 nm and the fluorescence quenching efficiency was closely related to the amount of LTL added to the QDs solution; they presented a linear relationship when the concentrations of LTL vary from 6 to 138 μM. The mechanism of the interaction between doped CdTe QDs and LTL was investigated and was confirmed to be a dynamic quenching mechanism. The proposed method was successfully applied to the determination of LTL, and satisfactory results were obtained.

In this paper, a novel method was developed for rapid and quantitative determination of cephalexin on the basis of the fluorescence quenching of L-cysteine capped core–shell CdTe/ZnS nanoparticles (NPs). The functionalized CdTe/ZnS NPs were successfully synthesized in aqueous solution. L-Cysteine capped CdTe/ZnS NPs were characterized by the means of X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Experimental results displayed that the fluorescence intensity of CdTe/ZnS NPs reduced in the presence of cephalexin due to interaction between L-cysteine capped CdTe/ZnS NPs and cephalexin, with the emission wavelength at about 665 nm. Under optimal conditions, the relative fluorescence intensity was linearly proportional to the concentration of cephalexin ranging from 3.4 × 10−6 to 1.0 × 10−4 M with a detection limit of 0.83 × 10−6 M. The L-cysteine capped CdTe/ZnS NPs fluorescence probe showed an obvious and good response to cephalexin, and the result was also satisfactory when it was applied to analyzing cephalexin in a real sample.

Cupric acetate/polyacrylonitrile composite nanofibers were prepared by electrospinning and hollow copper oxide (CuO) particles were produced after subsequent thermal treatment process. The electrospun hollow CuO particles modified carbon paste electrode (CPE) was demonstrated for the first time for nonenzymatic hydrogen peroxide (H(2)O(2)) sensor. The structures and morphologies of hollow CuO particles were characterized by scanning electron microscopy and X-ray diffraction spectrum. The assay performance of the modified sensor to H(2)O(2) was evaluated by cyclic voltammetry and amperometry, revealing high sensitivity (1746.50 μA mM(-1) cm(-2)), low detection limit (0.022 μM) and wide linear response of determination of H(2)O(2) oxidation in the range of 0.05 μM to 1.00 mM.

Process variation on lot-to-lot and wafer-to-wafer level has been well addressed using run-to-run control in advanced process control, however, to tackle the ever increasing die-to-die level process variation at the 65 nm technology and beyond, the process control must be extended into finer domain: die-to-die level. A novel model based process control approach is proposed to reduce the critical dimension(CD) variation on die-to-die level, i.e. across-wafer level. The central idea of the proposed approach is to compensate for upstream and downstream systematic CD variation by adjusting the across-wafer post-exposure bake (PEB) temperature profile of a multi-zone bake plate. A temperature-to-offset model relating the PEB temperature profile of multi-zone bake plate to its heater zone offsets was constructed experimentally using wireless temperature sensors from OnWafer Technologies. The baseline post-etch CD signature and plasma etch bias signature were extracted from the characterization experiment. A post-etch CD variation reduction of 40% was realized in the verification experiment, which validated the efficacy of the proposed approach. This CD variation control concept was further extended to simultaneous CD variation control for multiple CD features considering that multiple CD features coexist on a real chip, and CD variation control scheme based on multi-objective and minimax optimization is proposed to realize simultaneous CD variation control for multiple CD features. We also demonstrate through simulation using minimax optimization that across-wafer CD variation of multiple CD features can be significantly reduced for the 130 nm technology node and beyond.

Across-wafer gate critical dimension (CD) uniformity impacts chip-to-chip performance variation vis-a-vis speed and power. Performance specification for across-wafer CD uniformity has become increasingly stringent as linewidth decreases to 90 nm and below. This paper presents a novel approach to improve across-wafer gate CD uniformity through the lithography and etch process sequence. The proposed approach is to compensate for upstream and downstream systematic CD variation components in the litho-etch process sequence by optimizing across-wafer post exposure bake (PEB) temperature profiles. More precisely, we first construct a temperature-to-offset model that relates the PEB temperature profiles to the setpoint offsets of multi-zone PEB plates. A second model relating across-wafer CD to setpoint offsets of PEB plates is then identified from CD scanning electron microscope measurements. Post-develop and post-etch CD uniformity enhancement methodologies are then proposed based on the CD-to-offset model and temperature-to-offset models. The temperature-to-offset model is determined to be more appropriate for use in CD uniformity control due to its superior fidelity and portability as compared with the CD-to-offset model. We demonstrate that about 1-nm reduction in standard deviation of post-etch CD variation was achieved in the verification experiment, which validated the efficacy of proposed CD uniformity control approach.

We suggest a multiatom cavity quantum electrodynamics system for the detection of a weak magnetic field, based on Faraday rotation with intracavity electromagnetically induced transparency. Our study demonstrates that the collective coupling between the cavity modes and the atomic ensemble can be used to improve the sensitivity. With single-probe photon input, the sensitivity is inversely proportional to the number of atoms, and a sensitivity of 2.45 nT Hz–1/2 could be attained. With multiphoton measurement, our numerical calculations show that the magnetic field sensitivity can be improved to 105.6 aT Hz–1/2 with realistic experimental conditions.

We theoretically investigate steady-state behaviors of carbon nanotube quantum dots with spin-orbit coupling in a unidirectional ring cavity. Our results show that the spin-orbit coupling can induce optical bistability. In addition to the existence of spin-orbit coupling, switching optical bistability to optical multistability or vice versa is realized by adjusting detuning of the probe field. Our results show that the carbon nanotube quantum dots will possibly be a promising candidate for realizing all-optical switching.

Perovskite-type oxide LaNiO(3) nanofibers (LNFs) have been successfully synthesized by electrospinning and sequential calcinations. The electrospun LNFs modified carbon paste electrode was used to construct a nonenzymatic hydrogen peroxide (H(2)O(2)) sensor and glucose biosensor for the first time. The LNFs composition was verified by X-ray diffraction, and the morphologies were examined by scanning electron microscopy and transmission electron microscopy. Cyclic voltammetry and amperometry were used to evaluate the catalytic activity of the LNFs modified electrode towards H(2)O(2) and glucose. By using LNFs as electrocatalysts, the modified electrode showed high electrocatalytic activity for the oxidation of H(2)O(2) and glucose. Under the optimized conditions, the H(2)O(2) sensor exhibited a low detection limit down to 33.9 nM with a wide linear range from 0.05 to 1000 μM. The nonenzymatic sensor also showed fast response, long-term stability as well as a low detection limit for glucose.

As the semiconductor industry moves to the 45nm node and beyond, the tolerable lithography process window significantly shrinks due to the combined use of high NA and low k1 factor. This is exacerbated by the fact that the usable depth of focus at 45nm node for critical layer is 200nm or less. Traditional Optical Proximity Correction (OPC) only computes the optimal pattern layout to optimize its lithography patterning at nominal process condition (nominal defocus and nominal exposure dose) according to an OPC model calibrated at this nominal condition, and this may put the post-OPC layout at non-negligible patterning failure risk due to the inevitable process variation (mainly defocus and dose variations). With a little sacrifice at the nominal condition, process variation aware OPC can greatly enhance the robustness of post-OPC layout patterning in the presence of defocus and dose variation. There is also an increasing demand for through process window lithography verification for post-OPC circuit layout. The corner stone for successful process variation aware OPC and lithography verification is an accurately calibrated continuous process window model which is a continuous function of defocus and dose. This calibrated model needs to be able to interpolate and extrapolate in the usable process window. Based on Synopsys' OPC modeling software package-ProGen and ProGenPlus, we developed an automated process window (PW) modeling module, which can build process variation aware process window OPC model with continuously adjustable process parameters: defocus and dose. The calibration of this continuous PW model was performed in a single calibration process using silicon measurement at nominal condition and off-focus-off-dose conditions. Through the example of several process window models for layers at 45nm technology nodes, we demonstrated that this novel continuous PW modeling approach can achieve very good performance both at nominal condition and at interpolated or extrapolated off-focus-off-dose conditions.

The concept of focus blur encompasses the effect of laser bandwidth longitudinal chromatic aberration and scanner stage vertical vibration. The finite bandwidth of excimer laser source causes a corresponding finite distribution of focal planes in a range of 100nm or larger for the optical lithography system. Similarly, scanner vertical stage vibration puts the wafer in a finite distribution of focal planes. Both chromatic aberration and vertical stage vibration could introduce significant CD errors, hence can no longer be ignored in current lithography processes development and OPC development that require CD control within a few nanometers. We developed several methodologies to model the laser chromatic aberration and vertical stage vibration in OPC (Optical Proximity Correction) modeling tool. Extensive simulations were done to calculate chromatic aberration and vertical stage vibration focus blur's impact on lithography patterning for a variety of test structures. Chromatic aberration and vertical stage vibration focus blur effect was further included as an regression term in experimental OPC model calibration to capture its impact on litho patterning, and significant benefit to OPC model calibration was observed.

As the semiconductor industry enters the 45nm node and beyond, the tolerable lithography process window significantly shrinks due to the decreasing k 1 factor and increasing lens NA required to meet product shrink goals. The usable depth of focus at the 45nm node for critical layer is less than 200nm and for the 32nm node it will approach 100nm. Consequently, process window aware Optical Proximity Correction (OPC) and Lithography Rule Check (LRC) become crucial to ensure the robustness of OPC to focus and dose variation. An accurately calibrated continuous process window model is the corner stone for successful process variation aware OPC and LRC. For ease of use, this calibrated model should be a continuous function of defocus and dose and able to interpolate and extrapolate in the usable process window. Lithographic proximity effects have an optical component and a resist component. As state of the art OPC simulation tool is capable of precise and fast optical simulation, however its treatment of chemical amplified resist effects is relatively crude and does not capture the complex behavior during acid & quencher reaction, diffusion and development. This in turn causes difficulties for a continuous process window model where the resist component plays an important role. We proposed a hybrid resist model, which is a superposition of a traditional OPC chemical amplified resist model and a first order resist bias model. Using Synopsys' OPC modeling software package-ProGen, we incorporated this hybrid resist model into the continuous process window (PW) modeling module, and very good model calibration performance was achieved.

High NA and Ultra-High NA (NA>1.0) applications for low k1 imaging strongly demand the adoption of polarized illumination as a resolution enhancement technology since proper illumination polarization configuration can greatly improve the image contrast hence pattern printing fidelity and the effectiveness of optical proximity correction (OPC). However, current OPC/RET modeling software can only model the light source polarization of simple types, such as TE, TM, X, Y, or sector polarization with relatively simple configuration. Realistic polarized light used in scanners is more complex than the aforementioned simple ones. As a result, simulation accuracy and quality of the OPC result will be compromised by the simplification of the light source polarization modeling in the traditional approach. With ever shrinking CD error budget in the manufacturing of IC's at advanced technology nodes, more accurate and comprehensive illumination source modeling for lithography simulations and OPC/RET is needed. On the other hand, for polarized illumination to be fully effective, ideally all the components in the optical lithography system should not alter the polarization state of light during its propagation from illuminator to wafer surface. In current OPC modeling tools, it is typically assumed that the amplitude and polarization state of the light do not change as it passes through the projection lens pupil, i.e. the polarization aberration of projection lens pupil is ignored. However, in reality, the projection lens pupil of the scanner does change the amplitude and the polarization state to some extent, and ignorance of projection pupil induced polarization state and amplitude changes will cause CD errors un-tolerable at the 45nm device generation and beyond. We developed an OPC-deployable modeling approach to model arbitrarily polarized light source and arbitrarily polarized projection lens pupil. Based on polarization state vector descriptions of a general illumination source, this modeling approach unifies optical simulations of unpolarized, partially polarized, and completely polarized illuminations. The polarization aberration imposed by the projection lens pupil is modeled via Jones matrix format, and it is applicable to arbitrary polarization aberrations imposed by any components in the lithography system that can be characterized in Jones matrix format. Numerical experiments were performed to study CD impact from illumination polarization and projection lens pupil polarization aberrations, and up to several nanometers impact on optical proximity effect (OPE) was observed, which is not negligible given the extremely stringent CD error budget at 45nm node and beyond. Based on an experimentally measured Jones matrix pupil which intrinsically provides a much better approximation to the physical scanner projection pupil, we propose a more physics-centric methodology to evaluate the optical model accuracy of OPC simulator.

A thin membrane called a pellicle is commonly used to protect the mask from contamination. The thickness of the pellicle material is usually optimized at normal incident angle to minimize the thin film optics interference effect by cancellation of the reflected light from the top ambient/pellicle interface with the reflected light from the bottom pellicle/ambient interface. In previous lithography generations the maximum angle collected by the projection lens (NA) was low, hence the normal incidence approach was valid, and the transmission loss for the non-normal incident angles was minor and ignored. With modern hyper-NA imaging for 45nm and smaller nodes, this transmission attenuation becomes larger. The more stringent CD error budget of these technology nodes demands that this effect should not be ignored anymore. In this paper, we present a modeling framework that takes into consideration the high angle pellicle effects. Taking the pellicle's polarization state dependent transmission data, which can be measured or computed with a rigorous simulator, we first present the pellicle transmission property as Jones matrices on the pupil plane, and then incorporate pellicle modeling into the existing vector model for lithography imaging computation. Existing modeling software for modelbased OPC/RET tools is easily enhanced to include pellicle modeling. Using Synopsys' OPC/RET modeling software ProGen, we investigate the necessity of pellicle effect modeling for mask synthesis for 45 nm and smaller nodes. Numerical experiments are performed to study the impact of illumination polarization on the accuracy of lithography simulation and the quality of OPC results.

As the semiconductor industry moves to the 45nm node and beyond, the tolerable lithography process window significantly shrinks due to the combined use of high NA and low k 1 factor. This is exacerbated by the fact that the usable depth of focus at 45nm node for critical layer is 200nm or less. Traditional Optical Proximity Correction (OPC) only computes the optimal pattern layout to optimize its patterning at nominal process condition (nominal defocus and nominal exposure dose) according to an OPC model calibrated at this nominal condition, and this may put the post-OPC layout at nonnegligible patterning risk due to the inevitable process variation (defocus and dose variations). With a little sacrifice at the nominal condition, process variation aware OPC can greatly enhance the robustness of post-OPC layout patterning in the presence of defocus and dose variation. There is also an increasing demand for through process window lithography verification for post-OPC circuit layout. The corner stone for successful process variation aware OPC and lithography verification is an accurately calibrated continuous process window model which is a continuous function of defocus and dose. This calibrated model needs to be able to interpolate and extrapolate in the usable process window. Based on Synopsys' OPC modeling software package ProGen, we developed and implemented a novel methodology for continuous process window (PW) model, which has two continuous adjustable process parameters: defocus and dose. The calibration of this continuous PW model was performed in a single calibration process using silicon measurement at nominal condition and off-focus-off-dose conditions which are sparsely sampled within the measured entire focus exposure matrix (FEM). The silicon data at the off-focus-off-dose conditions not used for model calibration was utilized to validate the accuracy and stability of PW model during model interpolation and extrapolation. We demonstrated this novel continuous PW modeling approach can achieve very good performance both at nominal condition and at interpolated or extrapolated off-focus-off-dose conditions.

Production optical proximity correction (OPC) tools employ compact optical models in order to accurately predict complicated optical lithography systems with good theoretical accuracy. Theoretical accuracy is not the same as usable prediction accuracy in a real lithographic imaging system. Real lithographic systems have deviations from ideal behavior in the process, illumination, projection and mechanical systems as well as in metrology. The deviations from the ideal are small but non-negligible. For this study we use realistic process variations and scanner values to perform a detailed study of useful OPC model accuracy vs. the variation from ideal behavior and vs. theoretical OPC accuracy. The study is performed for different 32nm lithographic processes. The results clearly show that incorporating realistic process, metrology and imaging tool signatures is significantly more important to predictive accuracy than small improvements in theoretical accuracy.

The concept of focus blur encompasses the effect of laser bandwidth longitudinal chromatic aberration and scanner stage vertical vibration. The finite bandwidth of excimer laser source causes a corresponding finite distribution of focal planes in a range of 100nm or larger for the optical lithography system. Similarly, scanner vertical stage vibration puts the wafer in a finite distribution of focal planes. Both chromatic aberration and vertical stage vibration could introduce significant CD errors, hence can no longer be ignored in current lithography processes development and OPC development that require CD control within a few nanometers. We developed several methodologies to model the laser chromatic aberration and vertical stage vibration in OPC (Optical Proximity Correction) modeling tool. Extensive simulations were done to calculate chromatic aberration and vertical stage vibration focus blur's impact on lithography patterning for a variety of test structures. Chromatic aberration and vertical stage vibration focus blur effect was further included as an regression term in experimental OPC model calibration to capture its impact on litho patterning, and significant benefit to OPC model calibration was observed.

The increasingly stringent demand for shrinkage of IC device dimensions has been pushing the development of new resolution enhancement technologies in micro-lithography. High NA and Ultra-High NA (NA>1.0) applications for low k 1 imaging strongly demand the adoption of polarized illumination as a resolution enhancement technology since proper illumination polarization configuration can greatly improve the image contrast hence pattern printing fidelity. For polarized illumination to be fully effective, ideally all the components in the optical system should not alter the polarization state during propagation from illuminator to wafer surface. In current OPC modeling tools, it is typically assumed that the amplitude and polarization state of the electric field do not change as it passes through the projection lens pupil. However, in reality, the projection lens pupil of the scanner does change the amplitude and the polarization state to some extent, and ignorance of projection pupil induced polarization state and amplitude changes may cause CD errors which are un-tolerable at the 45nm device generation and beyond. We developed an OPC-deployable modeling approach to model polarization aberration imposed by the projection lens pupil via Jones matrix format. This polarization aberration modeling capability has been integrated into the Synopsys OPC modeling tool, ProGen, and its accuracy and efficiency have been validated by comparing with an industry standard lithography simulator SolidE. Our OPC simulations show that the impact of projection lens pupil polarization aberrations on optical proximity effect (OPE) could be as large as several nanometers, which is not negligible given the extremely stringent CD error budget at 45nm node and beyond. This modeling approach is applicable to arbitrary polarization aberrations imposed by any components in the lithography system that can be characterized in Jones matrix format. Based on an experimentally measured Jones matrix pupil which intrinsically provides a much better approximation to the physical scanner pupil, we propose a more physics-centric methodology to evaluate the optical model accuracy of OPC simulator.

The requirement for OPC modeling accuracy becomes increasingly stringent as the semiconductor industry enters sub- 0.1um regime. Targeting at capturing the IC pattern printing characteristics through the lithography process, an OPC model is usually in the form of the first principle optical imaging component, refined by some phenomenological components such as resist and etch. The phenomenological components can be adjusted appropriately in order to fit the OPC model to the silicon measurement data. The optical imaging component is the backbone for the OPC model, and it is the key to a stable and physics-centric OPC model. Scanner systematic signatures such as illuminator pupil-fill, illuminator polarization, lens aberration, lens apodization, flare, etc., previously ignored without significant accuracy sacrifice at previous technology nodes, but are playing non-negligible roles at 45nm node and beyond. In order to ensure that the OPC modeling tool can accurately model these important scanner systematic signatures, the core engine (i.e. the optical imaging simulator) of OPC simulator must be able to model these signatures with sufficient accuracy. In this paper, we study the impact on optical proximity effect (OPE) of the aforementioned scanner systematic signatures on several 1D (simple line space, doublet line and doublet space) and 2D (dense line end pullback, isolated line end pullback and T-bar line end pullback) OPC test patterns. We demonstrate that the scanner systematic signatures have significant OPE impact on the level of several nanometers. The predicted OPEs and impact from our OPC simulator matches well with results from an industry standard lithography simulator, and this has laid the foundation of accurate and physics-centric OPC model with the systematic scanner signatures incorporated.

An accurate process model has always been the key for successful implementation of model-based Optical Proximity Correction (OPC). As CD control requirements become severe at the 45nm and 32nm device generations, process model accuracy requirements become more stringent. In previous generations, certain systematic process and tool fingerprints could be safely ignored. For example, lens apodization and mask pellicle film induced transmission loss, lens vectorial fingerprint(i.e. Jones pupil), illuminator polarization profile, and etc were ignored in conventional OPC modeling approaches. These effects are now playing a more important role in OPC modeling as technology scales down. Using conventional OPC model may lead to under-correction of the design layout during OPC, and this will result in large number of post-OPC layout hot spots which have patterning issues when the OPCed layout is exposed on the scanner. We designed an OPC correction and verification flow which can efficiently capture the post-OPC layout hot spots due to under-correction using traditional OPC model, and this flow further fixes these detected hot spots. Our simulations demonstrated that this proposed flow is able to achieve an OPC performance of 2.25nm CD error range and 0.26nm CD error standard deviation on poly gate layer for 45nm SRAM design. And this validated the efficiency of the proposed flow.