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The incorporation of large numbers of chemically diverse functional components into microfabricated structures at precise locations is challenging; now the precision placement of DNA origami by directed self-assembly is shown to overcome this problem for the purpose of reliably and controllably coupling molecular emitters to photonic crystal cavities. Emitter-in-resonator devices for optical chips The incorporation of large numbers of chemically diverse functional components into microfabricated structures at precise locations is challenging. Paul Rothemund and colleagues now show that the directed self-assembly and placement of DNA origami can overcome this obstacle. The method enables reliable and controllable coupling of molecular emitters to photonic crystal cavities with high precision, with scalability illustrated by the successful fabrication of 65,536 independently programmed photonic crystal cavities on a single chip. These features, together with the modularity of DNA origami, suggest that the method is well suited to the rapid prototyping of a range of hybrid nanophotonic and other functional devices. Many hybrid devices integrate functional molecular or nanoparticle components with microstructures, as exemplified by the nanophotonic devices that couple emitters to optical resonators 1 for potential use in single-molecule detection 2 , 3 , precision magnetometry 4 , low threshold lasing 5 , 6 and quantum information processing 7 , 8 , 9 , 10 , 11 , 12 . These systems also illustrate a common difficulty for hybrid devices: although many proof-of-principle devices exist, practical applications face the challenge of how to incorporate large numbers of chemically diverse functional components into microfabricated resonators at precise locations. Here we show that the directed self-assembly 13 , 14 of DNA origami 15 onto lithographically patterned binding sites allows reliable and controllable coupling of molecular emitters to photonic crystal cavities (PCCs). The precision of this method is sufficient to enable us to visualize the local density of states within PCCs by simple wide-field microscopy and to resolve the antinodes of the cavity mode at a resolution of about one-tenth of a wavelength. By simply changing the number of binding sites, we program the delivery of up to seven DNA origami onto distinct antinodes within a single cavity and thereby digitally vary the intensity of the cavity emission. To demonstrate the scalability of our technique, we fabricate 65,536 independently programmed PCCs on a single chip. These features, in combination with the widely used modularity of DNA origami 16 , 17 , 18 , 19 , 20 , suggest that our method is well suited for the rapid prototyping of a broad array of hybrid nanophotonic devices.

Biological membrane channels mediate information exchange between cells and facilitate molecular recognition. While tuning the shape and function of membrane channels for precision molecular sensing via de-novo routes is complex, an even more significant challenge is interfacing membrane channels with electronic devices for signal readout, which results in low efficiency of information transfer - one of the major barriers to the continued development of high-performance bioelectronic devices. To this end, we integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces. Here we show that cholesterol modified DNA nanopores spontaneously and with remarkable affinity span the lipid bilayer formed over the planar bio-protonic electrode surface and mediate proton transport across the bilayer. Using the ability to easily modify DNA nanostructures, we illustrate that this bioprotonic device can be programmed for electronic recognition of biomolecular signals such as presence of Streptavidin and the cardiac biomarker B-type natriuretic peptide, without modifying the biomolecules. We anticipate this robust interface will allow facile electronic measurement and quantification of biomolecules in a multiplexed manner. Synthetic membrane channels have many potential applications, but interfacing membrane channels with electronic devices for efficient information transfer is challenging. Here the authors integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces.

High-frequency longitudinal RNA sequencing has emerged as a powerful approach for capturing dynamic transcriptional responses to therapeutic interventions, yet traditional differential expression analysis fails to identify genes with temporal variability that lack static expression differences. We used our previously developed computational framework for identifying Temporally Varying Genes (TVGs) from daily blood samples collected over 10–21 days in Sprague–Dawley rats treated with hepatotoxic compounds including tetracycline, isoniazid, carbon tetrachloride, and valproate. Our methodology employs variance-based scoring to detect genes exhibiting significant temporal fluctuations under treatment conditions. Unsupervised hierarchical clustering of TVGs identified three distinct temporal patterns: early-transient responses, sustained activation, and late-phase upregulation, each enriched for specific biological processes. Principal component analysis demonstrated clear treatment-induced transcriptomic shifts from baseline “Healthy Region” clusters to treatment-adapted “Response Region” states, with sample trajectories reflecting dose-dependent temporal dynamics. Cross-compound analysis revealed 186 commonly regulated genes across all treatments, representing conserved hepatotoxicity signatures, while compound-specific responses highlighted distinct mechanistic pathways. This approach enables kinetic-pharmacodynamic modeling that distinguishes primary drug targets from secondary adaptive responses, advancing precision medicine applications through dynamic molecular portraits of drug action and individual treatment variability.

The chemically synthesizable quantum emitters such as quantum dots (QDs), fluorescent nanodiamonds (FNDs), and organic fluorescent dyes can be integrated with an easy-to-craft quantum nanophotonic device, which would be readily developed by non-lithographic solution process. As a representative example, the solution dipping or casting of such soft quantum emitters on a flat metal layer and subsequent drop-casting of plasmonic nanoparticles can afford the quantum emitter-coupled plasmonic nanocavity (referred to as a nanoparticle-on-mirror (NPoM) cavity), allowing us for exploiting various quantum mechanical behaviors of light–matter interactions such as quantum electrodynamics (QED), strong coupling (e.g., Rabi splitting), and quantum mirage. This versatile, yet effective soft quantum nanophotonics would be further benefitted from a deterministic control over the positions and orientations of each individual quantum emitter, particularly at the molecule level of resolution. In this review, we will argue that DNA nanotechnology can provide a gold vista toward this end. A collective set of exotic characteristics of DNA molecules, including Watson-Crick complementarity and helical morphology, enables reliable grabbing of quantum emitters at the on-demand position and steering of their directors at the single molecular level. More critically, the recent advances in large-scale integration of DNA origami have pushed the reliance on the distinctly well-formed single device to the regime of the ultra-scale device arrays, which is critical for promoting the practically immediate applications of such soft quantum nanophotonics.

Light scattering phenomena in periodic systems have been investigated for decades in optics and photonics. Their classical description relies on Bragg scattering, which gives rise to constructive interference at specific wavelengths along well defined propagation directions, depending on illumination conditions, structural periodicity, and the refractive index of the surrounding medium. In this paper, by engineering multifrequency colorimetric responses in deterministic aperiodic arrays of nanoparticles, we demonstrate significantly enhanced sensitivity to the presence of a single protein monolayer. These structures, which can be readily fabricated by conventional Electron Beam Lithography, sustain highly complex structural resonances that enable a unique optical sensing approach beyond the traditional Bragg scattering with periodic structures. By combining conventional dark-field scattering micro-spectroscopy and simple image correlation analysis, we experimentally demonstrate that deterministic aperiodic surfaces with engineered structural color are capable of detecting, in the visible spectral range, protein layers with thickness of a few tens of Angstroms.

Over the last decade, DNA origami has matured into one of the most powerful bottom-up nanofabrication techniques. It enables both the fabrication of nanoparticles of arbitrary two-dimensional or three-dimensional shapes, and the spatial organization of any DNA-linked nanomaterial, such as carbon nanotubes, quantum dots, or proteins at ∼5-nm resolution. While widely used within the DNA nanotechnology community, DNA origami has yet to be broadly applied in materials science and device physics, which now rely primarily on top-down nanofabrication. In this article, we first introduce DNA origami as a modular breadboard for nanomaterials and then present a brief survey of recent results demonstrating the unique capabilities created by the combination of DNA origami with existing top-down techniques. Emphasis is given to the open challenges associated with each method, and we suggest potential next steps drawing inspiration from recent work in materials science and device physics. Finally, we discuss some near-term applications made possible by the marriage of DNA origami and top-down nanofabrication.

The future development of an AI scientist, a tool that is capable of integrating a variety of experimental data and generating testable hypotheses, holds immense potential. So far, bespoke machine learning models have been created to specialize in singular scientific tasks, but otherwise lack the flexibility of a general purpose model. Here, we show that a general purpose large language model, chatGPT 3.5-turbo, can be fine-tuned to learn the structural biophysics of DNA. We find that both fine-tuning models to return chain-of-thought responses and chaining together models fine-tuned for subtasks have an enhanced ability to analyze and design DNA sequences and their structures.

The control of light matter interaction in periodic and random media has been investigated in depth during the last few decades, yet structures with controlled degree of disorder such as Deterministic Aperiodic Nano Structures (DANS) have been relatively unexplored. DANS are characterized by non-periodic yet long-range correlated (deterministic) morphologies and can be generated by the mathematical rules of symbolic dynamics and number theory. In this thesis, I have experimentally investigated the unique light transport and localization properties in planar dielectric and metal (plasmonics) DANS. In particular, I have focused on the design, nanofabrication and optical characterization of DANS, formed by arranging metal/dielectric nanoparticles in an aperiodic lattice. This effort is directed towards development of on-chip nanophotonic applications with emphasis on label-free bio-sensing and enhanced light emission. The DANS designed as Surface Enhanced Raman Scattering (SERS) substrate is composed of multi-scale aperiodic nanoparticle arrays fabricated by e-beam lithography and are capable of reproducibly demonstrating enhancement factors as high as ∼107. Further improvement of SERS efficiency is achieved by combining DANS formed by top-down approach with bottom-up reduction of gold nanoparticles, to fabricate novel nanostructures called plasmonic “nano-galaxies” which increases the SERS enhancement factors by 2–3 orders of magnitude while preserving the reproducibility. In this thesis, along with presenting details of fabrication and SERS characterization of these “rationally designed” SERS substrates, I will also present results on using these substrates for detection of DNA nucleobases, as well as reproducible label-free detection of pathogenic bacteria with species specificity. In addition to biochemical detection, the combination of broadband light scattering behavior and the ability for the generation of reproducible high fields in DANS make these structures ideally suited for radiative engineering. In particular, I will present results on fabrication and optical characterization of aperiodic photonic and plasmonic crystals for radiative engineering in Si-compatible SiNx/Er:SiNx in the visible and NIR spectral range. This thesis work represents the first systematic investigation of novel nanophotonic and nanoplasmonic devices based on the engineering aperiodic order for optical label-free bio-sensing and radiative engineering application.

Classification of proteomic samples from sick and non-sick individuals is important for developing high-quality diagnostics of diseases. Creating shortlist of proteins useful for diagnostics is challenging. In this manuscript a simple algorithm of creating a multidimensional biomarker of health state based of scanning proteomics data is provided. The algorithm is applied to several existing publicly available datasets and demonstrates 9-protein indicator of atopic dermatitis, and 6-protein indicator of health failure.Competing Interest StatementThe authors have declared no competing interest.