Pinal, a 16-billion-parameter foundation model that produces protein candidates from natural-language functional descriptions, supports natural language as a high-level interface for candidate generation in protein design, enabling programmable exploration with reduced reliance on manually specified structural or sequence constraints.
Novel biosensors based on optical metasurfaces offer superior sensing performance in compact form factors, with transformative potential spanning biomedical research, clinical diagnostics and drug screening. However, their translation to real-world applications is hindered by a strong reliance on sophisticated and expensive top-down nanolithographic techniques with limited accessibility and low throughput. Here, we demonstrate scalable, high-throughput metasurfaces with optofluidic integration for label-free biosensing, exemplified by high-quality large-area gold nanohole arrays via nanosphere self-assembly lithography. Through comprehensive resonance analysis, we identified a surface plasmon polariton–Bloch wave mode that is both highly sensitive and experimentally accessible using cost-effective setups with incoherent visible light. Moreover, to improve the mass transport and analyte capture, we optimized the functionalization scheme, microfluidic design, and the metasurface placement within the microfluidic channel. The versatile meta-sensors were demonstrated with a broad range of targets, from biomolecules such as immunoglobulin G, streptavidin, to streptavidin-coated nanoparticles, which mimic virus particles and extracellular vesicles. By holistically improving the nanopatterning quality, functionalization efficiency and optofluidic integration, we achieved an experimental refractometric sensitivity of 498 nm/refractive index unit at 736 nm wavelength, a limit of detection of 0.17 ng/mL for biomolecules and ≲1 × 107 /mL for nanoparticles. These scalable, cost-effective meta-sensors deliver sensing performance, dynamic range, and stability comparable to, or even surpass, those of state-of-the-art devices fabricated using top-down lithography, thereby bridging the gap toward practical applications. Scalable, versatile optical sensors detect a broad range of biomolecules and particles without labels in real time. Integrated microfluidics boosts delivery and capture of rare targets on light-enhanced sensor surfaces. Sensors exceed leading devices while using low-cost, high-throughput manufacturing process and visible light setups. Cleanroom-free method makes advanced biosensing more accessible and affordable for real-world applications. Platform supports multiplexed, point-of-care, and potentially wearable or fiber-based clinical diagnostic tools. Scalable, versatile optical sensors detect a broad range of biomolecules and particles without labels in real time. Integrated microfluidics boosts delivery and capture of rare targets on light-enhanced sensor surfaces. Sensors exceed leading devices while using low-cost, high-throughput manufacturing process and visible light setups. Cleanroom-free method makes advanced biosensing more accessible and affordable for real-world applications. Platform supports multiplexed, point-of-care, and potentially wearable or fiber-based clinical diagnostic tools.
Three-dimensional protein crystals are ordered, porous macroscopic materials with potential applications in catalysis, biosensing, and biomedicine. However, most protein crystals are obtained by empirical screening, providing limited control over the lattice architecture, pore geometry or component composition that determine material function. Here, we present a modular strategy for the programmable design of highly porous, framework-like protein crystals using predefined protein-protein interactions. This strategy yielded over 30 distinct protein crystals, including single-component and multicomponent P213 and I213 lattices that grow to over 100 µm in size. Small-angle X-ray scattering and electron microscopy showed close agreement between experimental lattices and computational models. RFdiffusion-guided design generated isomorphous variants with matched lattice parameters, enabling coherent protein crystal alloys, epitaxial core–shell growth and reversible shell assembly. The designed crystals exhibit tunable mesoporous architectures, with limiting apertures of 2–18 nm, and support genetically encoded incorporation of fluorescent protein guests. These results establish a general route to programmable lattice engineering of protein crystals and position them as genetically encoded, compositionally tunable mesoporous materials.
Zhe Li, Shunzhi Wang, W. Sheffler et al.· bioRxiv· 0 citations
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