7 research outputs found

    Detecting 20 nm Wide Defects in Large Area Nanopatterns Using Optical Interferometric Microscopy

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    Due to the diffraction limited resolution and the presence of speckle noise, visible laser light is generally thought to be impractical for finding deep subwavelength defects in patterned semiconductor wafers. Here, we report on a nondestructive low-noise interferometric imaging method capable of detecting nanoscale defects within a wide field of view using visible light. The method uses a common-path laser interferometer and a combination of digital image processing techniques to produce 70 μm by 27 μm panoramic phase and amplitude images of the test nanopattern. Significant noise reduction and high sensitivity are achieved, which enables successful detection of several different types of sparse defects with sizes on the order of 20 nm wide by 100 nm long by 110 nm tall

    Engineered Nanovesicles Expressing Bispecific Single Chain Variable Fragments to Protect against SARS-CoV‑2 Infection

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    Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in high morbidity and mortality rates worldwide. Although the epidemic has been controlled in many areas and numerous patients have been successfully treated, the risk of reinfection persists due to the low neutralizing antibody titers and weak immune response. To provide long-term immune protection for infected patients, novel bispecific CB6/dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing nonintegrin (SIGN) nanovesicles (NVs) were constructed to target both the SARS-CoV-2 spike protein (S) and the DC receptors for virus neutralization and immune activation. Herein, we designed NVs expressing both CB6 and DC-SIGN single chain variable fragments (scFvs) on the surface to block SARS-CoV-2 invasion and activate DC function. Monophosphoryl lipid A (MPLA) was loaded into the CB6/DC-SIGN NVs as an adjuvant to promote this process. The CB6/DC-SIGN NVs prevented a pseudovirus expressing the S protein from infecting the target cells expressing high levels of angiotensin-converting enzyme 2 in vitro. Additionally, CB6/DC-SIGN NVs admixed with S-expressing pseudoviruses activated the DCs, which was promoted by the adjuvant MPLA loaded in the NVs. Using a mouse model, we also confirmed that the CB6/DC-SIGN NVs effectively improved the neutralizing antibody titer and inhibited the growth of tumors expressing the S protein after 3 weeks of treatment. This potential NV-based treatment not only exerts a blocking effect by binding the S protein in the short term but may also provide patients with long-term protection against secondary infections

    Visualization 1: Digital micromirror device-based laser-illumination Fourier ptychographic microscopy

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    The reconstruction of the sample information in spatial and Fourier domain implemented by running the self-developed software written in Matlab Originally published in Optics Express on 19 October 2015 (oe-23-21-26999

    Safe Staphylococcal Platform for the Development of Multivalent Nanoscale Vesicles against Viral Infections

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    Many viruses often have closely related yet antigenically distinct serotypes. An ideal vaccine against viral infections should induce a multivalent and protective immune response against all serotypes. Inspired by bacterial membrane vesicles (MVs) that carry different protein components, we constructed an <i>agr</i> locus deletion mutant of the <i>Staphylococcus aureus</i> strain (RN4220-Δagr) to reduce potential toxicity. Nanoscale vesicles derived from this strain (<sup>Δagr</sup>MVs) carry at least four major components that can deliver heterologous antigens. These components were each fused with a triple FLAG tag, and the tagged proteins could be incorporated into the <sup>Δagr</sup>MVs. The presentation levels were (3.43 ± 0.73)%, (5.07 ± 0.82)%, (2.64 ± 0.61)%, and (2.89 ± 0.74)% of the total <sup>Δagr</sup>MV proteins for Mntc-FLAG, PdhB-FLAG, PdhA-FLAG, and Eno-FLAG, respectively. With two DENV envelope E domain III proteins (EDIIIconA and EDIIIconB) as models, the DENV EDIIIconA and EDIIIconB delivered by two staphylococcal components were stably embedded in the <sup>Δagr</sup>MVs. Administration of such engineered <sup>Δagr</sup>MVs in mice induced antibodies against all four DENV serotypes. Sera from immunized mice protected Vero cells and suckling mice from a lethal challenge of DENV-2. This study will open up new insights into the preparation of multivalent nanosized viral vaccines against viral infections
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