Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity.

Brain metastases (BrMs) are the leading cause of death in patients with solid cancers. BrMs exhibit a highly immunosuppressive milieu and poor response to immunotherapies; however, the underlying mechanism remains largely unclear. Here, we show that upregulation of HSP47 in tumor cells drives metastatic colonization and outgrowth in the brain by creating an immunosuppressive microenvironment. HSP47-mediated collagen deposition in the metastatic niche promotes microglial polarization to the M2 phenotype via the α2ß1 integrin/nuclear factor κB pathway, which upregulates the anti-inflammatory cytokines and represses CD8+ T cell anti-tumor responses. Depletion of microglia reverses HSP47-induced inactivation of CD8+ T cells and abolishes BrM. Col003, an inhibitor disrupting HSP47-collagen association restores an anti-tumor immunity and enhances the efficacy of anti-PD-L1 immunotherapy in BrM-bearing mice. Our study supports that HSP47 is a critical determinant of M2 microglial polarization and immunosuppression and that blocking the HSP47-collagen axis represents a promising therapeutic strategy against brain metastatic tumors.

Metasurfaces integrated with a single-mode waveguide array for off-chip wavefront shaping.

Integration of metasurfaces and SOI (silicon-on-insulator) chips can leverage the advantages of both metamaterials and silicon photonics, enabling novel light shaping functionalities in planar, compact devices that are compatible with CMOS (complementary metal-oxide-semiconductor) production. To facilitate light extraction from a two-dimensional metasurface vertically into free space, the established approach is to use a wide waveguide. However, the multi-modal feature of such wide waveguides can render the device vulnerable to mode distortion. Here, we propose a different approach, where an array of narrow, single-mode waveguides is used instead of a wide, multi-mode waveguide. This approach tolerates nano-scatterers with a relatively high scattering efficiency, for example Si nanopillars that are in direct contact with the waveguides. Two example devices are designed and numerically studied as demonstrations: the first being a beam deflector that deflects light into the same direction regardless of the direction of input light, and the second being a light-focusing metalens. This work shows a straightforward approach of metasurface-SOI chip integration, which could be useful for emerging applications such as metalens arrays and neural probes that require off-chip light shaping from relatively small metasurfaces.

Deep-subwavelength gap modes in all-dielectric metasurfaces for high-efficiency and large-angle wavefront bending.

All-dielectric, phase-gradient metasurfaces manipulate light via a judiciously designed planar distribution of high and low refractive indices. In the established design approaches, the high-index elements play a dominant role, while the electromagnetic field existing between these elements is routinely viewed as either an incidental by-product or detrimental crosstalk. Here we propose an alternative approach that concentrates on exploring the low-index materials for wavefront shaping. In our Si metasurface, the low-index air gap between adjacent Si fins is judiciously tuned, while the high-index Si fins only have a single size across the whole metasurface. These gap modes provide the full 2π phase coverage, as well as high and relatively uniform transmission, at the deep-subwavelength scale. These characteristics are ideal for mapping a steep phase gradient, consequently suitable for high-efficiency and large-angle wavefront bending. This light manipulation capability is exemplified with numerical simulation in PW-SW (freely propagating wave to surface wave) conversion, where the wavefront is deflected by an angle of 90°. In the gap-mode meta-converters, the average unit size can be only 1/60 of free-space wavelength, an order of magnitude smaller than that of conventional all-dielectric metasurfaces. Their conversion efficiency can reach 68%, the highest value reported for any all-dielectric gradient metasurface THz converter.

Directional conversion of a THz propagating wave into surface waves in deformable metagratings.

Controllable conversion between propagating light waves and surface waves (SWs) has recently attracted significant research interests. This paper demonstrates, via numerical simulation, for the first time all-dielectric SW converters that possess a tunable and directional SW conversion efficiency. The SW converters contain multiple metagratings of Si pillars embedded in a deformable substrate. In the analysis, an infinitely large, bi-periodic metagrating under the illumination of linearly polarized light is considered first. The SW conversion efficiency of this metagrating can be modulated between 4.3% and 51.0% for incident light frequency at 0.8 THz by stretching the deformable substrate along the direction of SW propagation. Subsequently, two SW converters under circularly polarized light illumination are analyzed, where a similar level of efficiency modulation is retained in finite-sized metagratings. In these converters, only the metagrating channels along the stretch direction have a strong SW conversion efficiency, which can reach 40.4% after normalization against the effective grating area. The directivity, a parameter defined here to reveal the energy contrast among the output channels, reaches 38.6 in one of the converters. Due to its high tunability, high directivity and compact size, the SW converters may be used as tunable optical sensors and light couplers in the THz regime.

Coherently tunable metalens tweezers for optofluidic particle routing.

Nanophotonic particle manipulation exploits unique light shaping capabilities of nanophotonic devices to trap, guide, rotate and propel particles in microfluidic channels. Recent introduction of metalens into microfluidics research demonstrates the new capability of using nanophotonics devices for far-field optical manipulation. In this work we demonstrate, via numerical simulation, the first tunable metalens tweezers that function under dual-beam illumination. The phase profile of the metalens is modulated by controlling the relative strength and phase of the two coherent incident light beams. As a result, the metalens creates a thin sheet of focus inside a microchannel. Changes to the illumination condition allow the focus to be swept across the microchannel, thereby producing a controllable and reconfigurable path for particle transport. Particle routing in a Y-branch junction, for both nano- and microparticles, is evaluated as an example functionality for the tunable metalens tweezers. This work shows that tunable far-field particle manipulation can be achieved using near-field nano-engineering and coherent control, opening a new way for the integration of nanophotonics and microfluidics.

Nanoparticle trapping and routing on plasmonic nanorails in a microfluidic channel.

Plasmonic nanostructures hold great promise for enabling advanced optical manipulation of nanoparticles in microfluidic channels, resulting from the generation of strong and controllable light focal points at the nanoscale. A primary remaining challenge in the current integration of plasmonics and microfluidics is to transport trapped nanoparticles along designated routes. Here we demonstrate through numerical simulation a plasmonic nanoparticle router that can trap and route a nanoparticle in a microfluidic channel with a continuous fluidic flow. The nanoparticle router contains a series of gold nanostrips on top of a continuous gold film. The nanostrips support both localised and propagating surface plasmons under light illumination, which underpin the trapping and routing functionalities. The nanoparticle guiding at a Y-branch junction is enabled by a small change of 50 nm in the wavelength of incident light.