Ion detection in a DNA nanopore FET device.

An ion detection device that combines a DNA-origami nanopore and a field-effect transistor (FET) was designed and modeled to determine sensitivity of the nanodevice to the local cellular environment. Such devices could be integrated into a live cell, creating an abiotic-biotic interface integrated with semiconductor electronics. A continuum model is used to describe the behavior of ions in an electrolyte solution. The drift-diffusion equations are employed to model the ion distribution, taking into account the electric fields and concentration gradients. This was matched to the results from electric double layer theory to verify applicability of the model to a bio-sensing environment. The FET device combined with the nanopore is shown to have high sensitivity to ion concentration and nanopore geometry, with the electrical double layer behavior governing the device characteristics. A logarithmic relationship was found between ion concentration and a single FET current, generating up to 200 nA of current difference with a small applied bias.

DNA nanopores as artificial membrane channels for bioprotonics.

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.

Rational Fabrication of Nano-to-Microsphere Polycrystalline Opals Using Slope Self-Assembly.

Self-assembly of artificial opals has garnered significant interest as a facile nanofabrication technique capable of producing highly ordered structures for optical, electrochemical, biomolecular, and thermal applications. In these applications, the optimum opal particle diameter can vary by several orders of magnitude because the properties of the resultant structures depend strongly on the feature size. However, current opal fabrication techniques only produce high-quality structures over a limited range of sphere sizes or require complex processes and equipment. In this work, the rational and simple fabrication of polycrystalline opals with diameters between 500 nm and 10 µm was demonstrated using slope self-assembly of colloids suspended in ethanol-water. The role of the various process parameters was elucidated through a scaling-based model that accurately captures the variations of opal substrate coverage for spheres of size 2 µm or smaller. For spheres of 10 µm and larger, capillary forces were shown to play a key role in the process dynamics. Based on these insights, millimeter-scale monolayered opals were successfully fabricated, while centimeter-scale opals were possible with sparse sphere stacking or small uncovered areas. These insights provide a guide for the simple and fast fabrication of opals that can be used as optical coatings, templates for high power density electrodes, molecule templates, and high-performance thermo-fluidic devices.

Bench-Top Fabrication of Single-Molecule Nanoarrays by DNA Origami Placement.

Large-scale nanoarrays of single biomolecules enable high-throughput assays while unmasking the underlying heterogeneity within ensemble populations. Until recently, creating such grids which combine the advantages of microarrays and single-molecule experiments (SMEs) has been particularly challenging due to the mismatch between the size of these molecules and the resolution of top-down fabrication techniques. DNA origami placement (DOP) combines two powerful techniques to address this issue: (i) DNA origami, which provides a ∼100 nm self-assembled template for single-molecule organization with 5 nm resolution and (ii) top-down lithography, which patterns these DNA nanostructures, transforming them into functional nanodevices via large-scale integration with arbitrary substrates. Presently, this technique relies on state-of-the-art infrastructure and highly trained personnel, making it prohibitively expensive for researchers. Here, we introduce a cleanroom-free, $1 benchtop technique to create meso-to-macro-scale DNA origami nanoarrays using self-assembled colloidal nanoparticles, thereby circumventing the need for top-down fabrication. We report a maximum yield of 74%, 2-fold higher than the statistical limit of 37% imposed on non-specific molecular loading alternatives. Furthermore, we provide a proof-of-principle for the ability of this nanoarray platform to transform traditionally low-throughput, stochastic, single-molecule assays into high-throughput, deterministic ones, without compromising data quality. Our approach has the potential to democratize single-molecule nanoarrays and demonstrates their utility as a tool for biophysical assays and diagnostics.

Absolute and arbitrary orientation of single-molecule shapes.

DNA origami is a modular platform for the combination of molecular and colloidal components to create optical, electronic, and biological devices. Integration of such nanoscale devices with microfabricated connectors and circuits is challenging: Large numbers of freely diffusing devices must be fixed at desired locations with desired alignment. We present a DNA origami molecule whose energy landscape on lithographic binding sites has a unique maximum. This property enabled device alignment within 3.2° on silica surfaces. Orientation was absolute (all degrees of freedom were specified) and arbitrary (the orientation of every molecule was independently specified). The use of orientation to optimize device performance was shown by aligning fluorescent emission dipoles within microfabricated optical cavities. Large-scale integration was demonstrated with an array of 3456 DNA origami with 12 distinct orientations that indicated the polarization of excitation light.

Plasmonic nanostructures through DNA-assisted lithography.

Programmable self-assembly of nucleic acids enables the fabrication of custom, precise objects with nanoscale dimensions. These structures can be further harnessed as templates to build novel materials such as metallic nanostructures, which are widely used and explored because of their unique optical properties and their potency to serve as components of novel metamaterials. However, approaches to transfer the spatial information of DNA constructions to metal nanostructures remain a challenge. We report a DNA-assisted lithography (DALI) method that combines the structural versatility of DNA origami with conventional lithography techniques to create discrete, well-defined, and entirely metallic nanostructures with designed plasmonic properties. DALI is a parallel, high-throughput fabrication method compatible with transparent substrates, thus providing an additional advantage for optical measurements, and yields structures with a feature size of ~10 nm. We demonstrate its feasibility by producing metal nanostructures with a chiral plasmonic response and bowtie-shaped nanoantennas for surface-enhanced Raman spectroscopy. We envisage that DALI can be generalized to large substrates, which would subsequently enable scale-up production of diverse metallic nanostructures with tailored plasmonic features.

Engineering and mapping nanocavity emission via precision placement of DNA origami.

Many hybrid devices integrate functional molecular or nanoparticle components with microstructures, as exemplified by the nanophotonic devices that couple emitters to optical resonators for potential use in single-molecule detection, precision magnetometry low threshold lasing and quantum information processing. 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 of DNA origami 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, suggest that our method is well suited for the rapid prototyping of a broad array of hybrid nanophotonic devices.

Optimized assembly and covalent coupling of single-molecule DNA origami nanoarrays.

Artificial DNA nanostructures, such as DNA origami, have great potential as templates for the bottom-up fabrication of both biological and nonbiological nanodevices at a resolution unachievable by conventional top-down approaches. However, because origami are synthesized in solution, origami-templated devices cannot easily be studied or integrated into larger on-chip architectures. Electrostatic self-assembly of origami onto lithographically defined binding sites on Si/SiO2 substrates has been achieved, but conditions for optimal assembly have not been characterized, and the method requires high Mg2+ concentrations at which most devices aggregate. We present a quantitative study of parameters affecting origami placement, reproducibly achieving single-origami binding at 94±4% of sites, with 90% of these origami having an orientation within ±10° of their target orientation. Further, we introduce two techniques for converting electrostatic DNA-surface bonds to covalent bonds, allowing origami arrays to be used under a wide variety of Mg2+-free solution conditions.

Spatial and spectral detection of protein monolayers with deterministic aperiodic arrays of metal nanoparticles.

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.

Spectral analysis of induced color change on periodically nanopatterned silk films.

We demonstrate controllable structural color based on periodic nanopatterned 2D lattices in pure protein films of silk fibroin. We show here periodic lattices in silk fibroin films with feature sizes of hundreds of nanometers that exhibit different colors as a function of varying lattice spacing. Further, when varying the index of refraction contrast between the nanopatterned lattice and its surrounding environment by applying liquids on top of the lattices, colorimetric shifts are observed. The effect is characterized experimentally and theoretically and a simple example of glucose concentration sensing is presented. This is the first example of a functional sensor based on silk fibroin optics.

Plasmonic nanogalaxies: multiscale aperiodic arrays for surface-enhanced Raman sensing.

The accurate and reproducible control of intense electromagnetic fields localized on the nanoscale is essential for the engineering of optical sensors based on the surface-enhanced Raman scattering (SERS) effect. In this paper, using rigorous generalized Mie theory (GMT) calculations and a combined top-down/bottom-up nanofabrication approach, we design and experimentally demonstrate approximately 10(8) spatially averaged, reproducible SERS enhancement in deterministic aperiodic arrays of Au nanoparticles with different length scales. Deterministic aperiodic arrays of 200 nm diameter nanocylinders are first fabricated using electron-beam lithography on quartz substrates, and smaller size (30 nm diameter) Au nanoparticles are subsequently positioned by in situ Au reduction at regions of maximum field enhancement. These multiscale structures, which we call "plasmonic nanogalaxies", feature a cascade enhancement effect due to the strong electromagnetic interactions of small satellite nanoparticles with localized fields in aperiodic arrays of nanocylinders. The development of SERS substrates based on aperiodic arrays with different length scales provides a novel strategy to engineer plasmon-enhanced biosensors with chemical fingerprinting capability.

Deterministic aperiodic arrays of metal nanoparticles for surface-enhanced Raman scattering (SERS).

Deterministic Aperiodic (DA) arrays of gold (Au) nanoparticles are proposed as a novel approach for the engineering of reproducible surface enhanced Raman scattering (SERS) substrates. A set of DA and periodic arrays of cylindrical and triangular Au nanoparticles with diameters ranging between 50-110 nm and inter-particle separations between 25-100 nm were fabricated by e-beam lithography on quartz substrates. Using a molecular monolayer of pMA (p-mercaptoaniline) as a Raman reporter, we show that higher values of SERS enhancement factors can be achieved in DA structures compared to their periodic counterparts, and discuss the specific scaling rules of DA arrays with different morphologies. Electromagnetic field calculations based on the semi-analytical generalized Mie theory (GMT) fully support our findings and demonstrate the importance of morphology-dependent diffractive coupling (long-range interactions) for the engineering of the SERS response of DA arrays. Finally, we discuss optimization strategies based on the control of particles sizes and shapes, and we demonstrate that spatially-averaged SERS enhancement factors of the order of approximately 10(7) can be reproducibly obtained using DA arrays of Au nano-triangles. The ability to rigorously design lithographically fabricated DA arrays of metal nanoparticles enables the optimization and control of highly localized plasmonic fields for a variety of chip-scale devices, such as more reproducible SERS substrates, label-free bio-sensors and non-linear elements for nano-plasmonics.

Photonic-plasmonic scattering resonances in deterministic aperiodic structures.

In this paper, we combine experimental dark-field scattering spectroscopy and accurate electrodynamics calculations to investigate the scattering properties of two-dimensional plasmonic lattices based on the concept of aperiodic order. In particular, by discussing visible light scattering from periodic, Fibonacci, Thue-Morse and Rudin-Shapiro lattices fabricated by electron-beam lithography on transparent quartz substrates, we demonstrate that deterministic aperiodic Au nanoparticle arrays give rise to broad plasmonic resonances spanning the entire visible spectrum. In addition, we show that far-field diffractive coupling is responsible for the formation of characteristic photonic-plasmonic scattering modes in aperiodic arrays of metal nanoparticles. Accurate scattering simulations based on the generalized Mie theory approach support our experimental results. The possibility of engineering complex metal nanoparticle arrays with distinctive plasmonic resonances extending across the entire visible spectrum can have a significant impact on the design and fabrication of novel nanodevices based on broadband plasmonic enhancement.

Quasi-periodic distribution of plasmon modes in two-dimensional Fibonacci arrays of metal nanoparticles.

In this paper we investigate for the first time the near-field optical behavior of two-dimensional Fibonacci plasmonic lattices fabricated by electron-beam lithography on transparent quartz substrates. In particular, by performing near-field optical microscopy measurements and three dimensional Finite Difference Time Domain simulations we demonstrate that near-field coupling of nanoparticle dimers in Fibonacci arrays results in a quasi-periodic lattice of localized nanoparticle plasmons. The possibility to accurately predict the spatial distribution of enhanced localized plasmon modes in quasi-periodic Fibonacci arrays can have a significant impact for the design and fabrication of novel nano-plasmonics devices.

Optical gap formation and localization properties of optical modes in deterministic aperiodic photonic structures.

We theoretically investigate the spectral and localization properties of two-dimensional (2D) deterministic aperiodic (DA) arrays of photonic nanopillars characterized by singular continuous (Thue-Morse sequence) and absolutely continuous (Rudin-Shapiro sequence) Fourier spectra. A rigorous and efficient numerical technique based on the 2D Generalized Multiparticle Mie Theory is used to study the formation of optical gaps and the confinement properties of eigenmodes supported by DA photonic lattices. In particular, we demonstrate the coexistence of optical modes with various degrees of localization (localized, extended and critical) and show that in-plane and out-of-plane optical energy confinement of extended critical modes can be optimally balanced. These results make aperiodic photonic structures very attractive for the engineering of novel passive and active photonic devices, such as low-threshold microlasers, sensitive detectors and bio-chemical sensors.