A general strategy for self-assembly of nanosized building blocks on liquid/liquid interfaces

A family of water/oil interfaces is introduced to provide effective platforms for rapid fabrication of large-area self-assembled nanofilms composed of various nanosized building blocks, including nanoparticles (NPs), nanocubes (NC), nanowires (NWs), and nanosheets, at room temperature. As a general interfacial assembly method, NWs and NPs are co-assembled at the liquid/liquid interface. The as-prepared co-assembled Ag NW and Ag NC films show high surface-enhanced Raman spectroscopy (SERS) intensity, the SERS performance being strongly dependent on the number ratio of the two kinds of nanosized building blocks. The results demonstrate that this interfacial system provides a general method for the assembly of various nanosized building blocks with different shapes and dimensionalities, and thus paves an alternative pathway for further applications of macroscopic assemblies with different functionalities.     

Ordered Arrangement and Optical Properties of Silica‐Stabilized Gold Nanoparticle–PNIPAM Core–Satellite Clusters for Sensitive Raman Detection

Gold–polymer hybrid nanoparticles attract wide interest as building blocks for the engineering of photonic materials and plasmonic (active) metamaterials with unique optical properties. In particular, the coupling of the localized surface plasmon resonances of individual metal nanostructures in the presence of nanometric gaps can generate highly enhanced and confined electromagnetic fields, which are frequently exploited for metal‐enhanced light–matter interactions. The optical properties of plasmonic structures can be tuned over a wide range of properties by means of their geometry and the size of the inserted nanoparticles as well as by the degree of order upon assembly into 1D, 2D, or 3D structures. Here, the synthesis of silica‐stabilized gold–poly(N‐isopropylacrylamide) (SiO₂‐Au‐PNIPAM) core–satellite superclusters with a narrow size distribution and their incorporation into ordered self‐organized 3D assemblies are reported. Significant alterations of the plasmon resonance are found for different assembled structures as well as strongly enhanced Raman signatures are observed. In a series of experiments, the origin of the highly enhanced signals can be assigned to the interlock areas of adjacent SiO₂‐Au‐PNIPAM core–satellite clusters and their application for highly sensitive nanoparticle‐enhanced Raman spectroscopy is demonstrated.     

Split‐GFP: SERS Enhancers in Plasmonic Nanocluster Probes

The assembly of plasmonic metal nanoparticles into hot spot surface‐enhanced Raman scattering (SERS) nanocluster probes is a powerful, yet challenging approach for ultrasensitive biosensing. Scaffolding strategies based on self‐complementary peptides and proteins are of increasing interest for these assemblies, but the electronic and the photonic properties of such hybrid nanoclusters remain difficult to predict and optimize. Here, split‐green fluorescence protein (sGFP) fragments are used as molecular glue and the GFP chromophore is used as a Raman reporter to assemble a variety of gold nanoparticle (AuNP) clusters and explore their plasmonic properties by numerical modeling. It is shown that GFP seeding of plasmonic nanogaps in AuNP/GFP hybrid nanoclusters increases near‐field dipolar couplings between AuNPs and provides SERS enhancement factors above 10⁸. Among the different nanoclusters studied, AuNP/GFP chains allow near‐infrared SERS detection of the GFP chromophore imidazolinone/exocyclic C?C vibrational mode with theoretical enhancement factors of 10⁸–10⁹. For larger AuNP/GFP assemblies, the presence of non‐GFP seeded nanogaps between tightly packed nanoparticles reduces near‐field enhancements at Raman active hot spots, indicating that excessive clustering can decrease SERS amplifications. This study provides rationales to optimize the controlled assembly of hot spot SERS nanoprobes for remote biosensing using Raman reporters that act as molecular glue between plasmonic nanoparticles.     

Bimetallic Nanostructures as Active Raman Markers: Gold‐Nanoparticle Assembly on 1D and 2D Silver Nanostructure Surfaces

It is demonstrated that bimetallic silver–gold anisotropic nanostructures can be easily assembled from various nanoparticle building blocks with well‐defined geometries by means of electrostatic interactions. One‐dimensional (1D) silver nanowires, two‐dimensional (2D) silver nanoplates, and spherical gold nanoparticles are used as representative building blocks for bottom‐up assembly. The gold nanoparticles are electrostatically bound onto the 1D silver nanowires and the 2D silver nanoplates to give bimetallic nanostructures. The unique feature of the resulting nanostructures is the particle‐to‐particle interaction that subjects absorbed analytes to an enhanced electromagnetic field with strong polarization dependence. The Raman activity of the bimetallic nanostructures is compared with that of the individual nanoparticle blocks by using rhodamine 6G solution as the model analyte. The Raman intensity of the best‐performing silver–gold nanostructure is comparable with the dense array of silver nanowires and silver nanoplates that were prepared by means of the Langmuir–Blodgett technique. An optimized design of a single‐nanostructure substrate for surface‐enhanced Raman spectroscopy (SERS), based on a wet‐assembly technique proposed here, can serve as a compact and low‐cost alternative to fabricated nanoparticle arrays.     

Non-lithographic SERS substrates: tailoring surface chemistry for Au nanoparticle cluster assembly

Near‐field plasmonic coupling and local field enhancement in metal nanoarchitectures, such as arrangements of nanoparticle clusters, have application in many technologies from medical diagnostics, solar cells, to sensors. Although nanoparticle‐based cluster assemblies have exhibited signal enhancements in surface‐enhanced Raman scattering (SERS) sensors, it is challenging to achieve high reproducibility in SERS response using low‐cost fabrication methods. Here an innovative method is developed for fabricating self‐organized clusters of metal nanoparticles on diblock copolymer thin films as SERS‐active structures. Monodisperse, colloidal gold nanoparticles are attached via a crosslinking reaction on self‐organized chemically functionalized poly(methyl methacrylate) domains on polystyrene‐block‐poly(methyl methacrylate) templates. Thereby nanoparticle clusters with sub‐10‐nanometer interparticle spacing are achieved. Varying the molar concentration of functional chemical groups and crosslinking agent during the assembly process is found to affect the agglomeration of Au nanoparticles into clusters. Samples with a high surface coverage of nanoparticle cluster assemblies yield relative enhancement factors on the order of 10⁹ while simultaneously producing uniform signal enhancements in point‐to‐point measurements across each sample. High enhancement factors are associated with the narrow gap between nanoparticles assembled in clusters in full‐wave electromagnetic simulations. Reusability for small‐molecule detection is also demonstrated. Thus it is shown that the combination of high signal enhancement and reproducibility is achievable using a completely non‐lithographic fabrication process, thereby producing SERS substrates having high performance at low cost.     

Self‐Assembled Large Au Nanoparticle Arrays with Regular Hot Spots for SERS

The cost‐effective self‐assembly of 80 nm Au nanoparticles (NPs) into large‐domain, hexagonally close‐packed arrays for high‐sensitivity and high‐fidelity surface‐enhanced Raman spectroscopy (SERS) is demonstrated. These arrays exhibit specific optical resonances due to strong interparticle coupling, which are well reproduced by finite‐difference time‐domain (FDTD) simulations. The gaps between NPs form a regular lattice of hot spots that enable a large amplification of both photoluminescence and Raman signals. At smaller wavelengths the hot spots are extended away from the minimum‐gap positions, which allows SERS of larger analytes that do not fit into small gaps. Using CdSe quantum dots (QDs) a 3–5 times larger photoluminescence enhancement than previously reported is experimentally demonstrated and an unambiguous estimate of the electromagnetic SERS enhancement factor of ≈10⁴ is obtained by direct scanning electron microscopy imaging of QDs responsible for the Raman signal. Much stronger enhancement of ≈10⁸ is obtained at larger wavelengths for benzenethiol molecules penetrating the NP gaps.     

Tubulin Double Helix: Lateral and Longitudinal Curvature Changes of Tubulin Protofilament

By virtue of their native structures, tubulin dimers are protein building blocks that are naturally preprogrammed to assemble into microtubules (MTs), which are cytoskeletal polymers. Here, polycation‐directed (i.e., electrostatically tunable) assembly of tubulins is demonstrated by conformational changes to the tubulin protofilament in longitudinal and lateral directions, creating tubulin double helices and various tubular architectures. Synchrotron small‐angle X‐ray scattering and transmission electron microscopy reveal a remarkable range of nanoscale assembly structures: single‐ and double‐layered double‐helix tubulin tubules. The phase transitions from MTs to the new assemblies are dependent on the size and concentration of polycations. Two characteristic scales that determine the number of observed phases are the size of polycation compared to the size of tubulin (≈4 nm) and to MT diameter (≈25 nm). This work suggests the feasibility of using polycations that have scissor‐ and glue‐like properties to achieve “programmable breakdown” of protein nanotubes, tearing MTs into double‐stranded tubulins and building up previously undiscovered nanostructures. Importantly, a new role of tubulins is defined as 2D shape‐controllable building blocks for supramolecular architectures. These findings provide insight into the design of protein‐based functional materials, for example, as metallization templates for nanoscale electronic devices, molecular screws, and drug delivery vehicles.     

A Versatile Route to Assemble Semiconductor Nanoparticles into Functional Aerogels by Means of Trivalent Cations

3D nanoparticle assemblies offer a unique platform to enhance and extend the functionality and optical/electrical properties of individual nanoparticles. Especially, a self‐supported, voluminous, and porous macroscopic material built up from interconnected semiconductor nanoparticles provides new possibilities in the field of sensing, optoelectronics, and photovoltaics. Herein, a method is demonstrated for assembling semiconductor nanoparticle systems containing building blocks possessing different composition, size, shape, and surface ligands. The method is based on the controlled destabilization of the particles triggered by trivalent cations (Y³⁺, Yb³⁺, and Al³⁺). The effect of the cations is investigated via X‐ray photoelectron spectroscopy. The macroscopic, self‐supported aerogels consist of the hyperbranched network of interconnected CdSe/CdS dot‐in‐rods, or CdSe/CdS as well as CdSe/CdTe core‐crown nanoplatelets is used to demonstrate the versatility of the procedure. The non‐oxidative assembly method takes place at room temperature without thermal activation in several hours and preserves the shape and the fluorescence of the building blocks. The assembled nanoparticle network provides longer exciton lifetimes with retained photoluminescence quantum yields, that make these nanostructured materials a perfect platform for novel multifunctional 3D networks in sensing. Various sets of photoelectrochemical measurements on the interconnected semiconductor nanorod structures also reveal the enhanced charge carrier separation.     

Self‐Assembly of Shaped Nanoparticles into Free‐Standing 2D and 3D Superlattices

This article describes a novel supramolecular assembly‐mediated strategy for the organization of Au nanoparticles (NPs) with different shapes (e.g., spheres, rods, and cubes) into large‐area, free‐standing 2D and 3D superlattices. This robust approach involves two major steps: (i) the organization of polymer‐tethered NPs within the assemblies of supramolecular comblike block copolymers (CBCPs), and (ii) the disassembly of the assembled CBCP structures to produce free‐standing NP superlattices. It is demonstrated that the crystal structures and lattice constants of the superlattices can be readily tailored by varying the molecular weight of tethered polymers, the volume fraction of NPs, and the matrix of CBCPs. This template‐free approach may open a new avenue for the assembly of NPs into 2D and 3D structures with a wide range of potential applications.     

Mastering Dendrimer Self‐Assembly for Efficient siRNA Delivery: From Conceptual Design to In Vivo Efficient Gene Silencing

Self‐assembly is a fundamental concept and a powerful approach in molecular science. However, creating functional materials with the desired properties through self‐assembly remains challenging. In this work, through a combination of experimental and computational approaches, the self‐assembly of small amphiphilic dendrons into nanosized supramolecular dendrimer micelles with a degree of structural definition similar to traditional covalent high‐generation dendrimers is reported. It is demonstrated that, with the optimal balance of hydrophobicity and hydrophilicity, one of the self‐assembled nanomicellar systems, totally devoid of toxic side effects, is able to deliver small interfering RNA and achieve effective gene silencing both in cells – including the highly refractory human hematopoietic CD34⁺ stem cells – and in vivo, thus paving the way for future biomedical implementation. This work presents a case study of the concept of generating functional supramolecular dendrimers via self‐assembly. The ability of carefully designed and gauged building blocks to assemble into supramolecular structures opens new perspectives on the design of self‐assembling nanosystems for complex and functional applications.     

Directing Gold Nanoparticles into Free‐Standing Honeycomb‐Like Ordered Mesoporous Superstructures

2D mesoporous materials fabricated via the assembly of nanoparticles (NPs) not only possess the unique properties of nanoscale building blocks but also manifest additional collective properties due to the interactions between NPs. In this work, reported is a facile and designable way to prepare free‐standing 2D mesoporous gold (Au) superstructures with a honeycomb‐like configuration. During the fabrication process, Au NPs with an average diameter of 5.0 nm are assembled into a superlattice film on a diethylene glycol substrate. Then, a subsequent thermal treatment at 180 °C induces NP attachment, forming the honeycomb‐like ordered mesoporous Au superstructures. Each individual NP connects with three neighboring NPs in the adjacent layer to form a tetrahedron‐based framework. Mesopores confined in the superstructure have a uniform size of 3.5 nm and are arranged in an ordered hexagonal array. The metallic bonding between Au NPs increases the structural stability of architected superstructures, allowing them to be easily transferred to various substrates. In addition, electron energy‐loss spectroscopy experiments and 3D finite‐difference time‐domain simulations reveal that electric field enhancement occurs at the confined mesopores when the superstructures are excited by light, showing their potential in nano‐plasmonic applications.     

Coordination‐Driven Hierarchical Assembly of Hybrid Nanostructures Based on 2D Materials

2D materials have received tremendous scientific and engineering interests due to their remarkable properties and broad‐ranging applications such as energy storage and conversion, catalysis, biomedicine, electronics, and so forth. To further enhance their performance and endow them with new functions, 2D materials are proposed to hybridize with other nanostructured building blocks, resulting in hybrid nanostructures with various morphologies and structures. The properties and functions of these hybrid nanostructures depend strongly on the interfacial interactions between 2D materials and other building blocks. Covalent and coordination bonds are two strong interactions that hold high potential in constructing these robust hybrid nanostructures based on 2D materials. However, most 2D materials are chemically inert, posing problems for the covalent assembly with other building blocks. There are usually coordination atoms in most of 2D materials and their derivatives, thus coordination interaction as a strong interfacial interaction has attracted much attention. In this review, recent progress on the coordination‐driven hierarchical assembly based on 2D materials is summarized, focusing on the synthesis approaches, various architectures, and structure–property relationship. Furthermore, insights into the present challenges and future research directions are also presented.     

Reversible Anion‐Driven Switching of an Organic 2D Crystal at a Solid–Liquid Interface

Ionic self‐assembly of charged molecular building blocks relies on the interplay between long‐range electrostatic forces and short‐range, often cooperative, supramolecular interactions, yet has been seldom studied in two dimensions at the solid–liquid interface. Here, we demonstrate anion‐driven switching of two‐dimensional (2D) crystal structure at the Au(111)/octanoic acid interface. Using scanning tunneling microscopy (STM), three organic salts with identical polyaromatic cation (PQPC₆⁺) but different anions (perchlorate, anthraquinonedisulfonate, benzenesulfonate) are shown to form distinct, highly ordered self‐assembled structures. Reversible switching of the supramolecular arrangement is demonstrated by in situ exchange of the anion on the pre‐formed adlayer, by changing the concentration ratio between the incoming and outgoing anion. Density functional theory (DFT) calculations reveal that perchlorate is highly mobile in the adlayer, and corroborate why this anion is only resolved transiently in STM. Surprisingly, the templating effect of the anion persists even where it does not become part of the adlayer 2D fabric, which we ascribe to differences in stabilization of cation conformations by the anion. Our results provide important insight into the structuring of mixed anion–cation adlayers. This is essential in the design of tectons for ionic self‐assembled superstructures and biomimetic adaptive materials and valuable also to understand adsorbate–adsorbate interactions in heterogeneous catalysis.     

Effective Light Directed Assembly of Building Blocks with Microscale Control

Light‐directed forces have been widely used to pattern micro/nanoscale objects with precise control, forming functional assemblies. However, a substantial laser intensity is required to generate sufficient optical gradient forces to move a small object in a certain direction, causing limited throughput for applications. A high‐throughput light‐directed assembly is demonstrated as a printing technology by introducing gold nanorods to induce thermal convection flows that move microparticles (diameter = 40 µm to several hundreds of micrometers) to specific light‐guided locations, forming desired patterns. With the advantage of effective light‐directed assembly, the microfluidic‐fabricated monodispersed biocompatible microparticles are used as building blocks to construct a structured assembly (≈10 cm scale) in ≈2 min. The control with microscale precision is approached by changing the size of the laser light spot. After crosslinking assembly of building blocks, a novel soft material with wanted pattern is approached. To demonstrate its application, the mesenchymal stem‐cell‐seeded hydrogel microparticles are prepared as functional building blocks to construct scaffold‐free tissues with desired structures. This light‐directed fabrication method can be applied to integrate different building units, enabling the bottom‐up formation of materials with precise control over their internal structure for bioprinting, tissue engineering, and advanced manufacturing.     

Flexible Fabrication of Shape‐Controlled Collagen Building Blocks for Self‐Assembly of 3D Microtissues

Creating artificial tissue‐like structures that possess the functionality, specificity, and architecture of native tissues remains a big challenge. A new and straightforward strategy for generating shape‐controlled collagen building blocks with a well‐defined architecture is presented, which can be used for self‐assembly of complex 3D microtissues. Collagen blocks with tunable geometries are controllably produced and released via a membrane‐templated microdevice. The formation of functional microtissues by embedding tissue‐specific cells into collagen blocks with expression of specific proteins is described. The spontaneous self‐assembly of cell‐laden collagen blocks into organized tissue constructs with predetermined configurations is demonstrated, which are largely driven by the synergistic effects of cell–cell and cell–matrix interactions. This new strategy would open up new avenues for the study of tissue/organ morphogenesis, and tissue engineering applications.     

3D Nanofabrication via Chemo‐Mechanical Transformation of Nanocrystal/Bulk Heterostructures

Planar nanocrystal/bulk heterostructures are transformed into 3D architectures by taking advantage of the different chemical and mechanical properties of nanocrystal and bulk thin films. Nanocrystal/bulk heterostructures are fabricated via bottom‐up assembly and top‐down fabrication. The nanocrystals are capped by long ligands introduced in their synthesis, and therefore their surfaces are chemically addressable, and their assemblies are mechanically “soft,” in contrast to the bulk films. Chemical modification of the nanocrystal surface, exchanging the long ligands for more compact chemistries, triggers large volume shrinkage of the nanocrystal layer and drives bending of the nanocrystal/bulk heterostructures. Exploiting the differential chemo‐mechanical properties of nanocrystal and bulk materials, the scalable fabrication of designed 3D, cell‐sized nanocrystal/bulk superstructures is demonstrated, which possess unique functions derived from nanocrystal building blocks.     

Tuning the Amphiphilicity of Building Blocks: Controlled Self‐Assembly and Disassembly for Functional Supramolecular Materials

Amphiphilicity is one of the molecular bases for self‐assembly. By tuning the amphiphilicity of building blocks, controllable self‐assembly can be realized. This article reviews different routes for tuning amphiphilicity and discusses different possibilities for self‐assembly and disassembly in a controlled manner. In general, this includes irreversible and reversible routes. The irreversible routes concern irreversible reactions taking place on the building blocks and changing their molecular amphiphilicity. The building blocks are then able to self‐assemble to form different supramolecular structures, but cannot remain stable upon loss of amphiphilicity. Compared to the irreversible routes, the reversible routes are more attractive due to the good control over the assembly and disassembly of the supramolecular structure formed via tuning of the amphiphilicity. These routes involve reversible chemical reactions and supramolecular approaches, and different external stimuli can be used to trigger reversible changes of amphiphilicity, including light, redox, pH, and enzymes. It is anticipated that this line of research can lead to the fabrication of new functional supramolecular assemblies and materials.     

Polymer–Lipid Hybrid Vesicles and Their Interaction with HepG2 Cells

Polymer–lipid hybrid vesicles are an emerging type of nano‐assemblies that show potential as artificial organelles among others. Phospholipids and poly(cholesteryl methacrylate)‐block‐poly(methionine methacryloyloxyethyl ester (METMA)—random–2‐carboxyethyl acrylate (CEA)) labeled with a Förster resonance energy transfer (FRET) reporter pair are used for the assembly of small and giant hybrid vesicles with homogenous distribution of both building blocks in the membrane as confirmed by the FRET effect. These hybrid vesicles have no inherent cytotoxicity when incubated with HepG2 cells up to 1.1 × 10¹¹ hybrid vesicles per mL, and they are internalized by the cells. In contrast to the fluorescent signal originating from the block copolymer, the fluorescent signal coming from the lipids is barely detectable in cells incubated with hybrid vesicles for 6 h followed by 24 h in cell media, suggesting that the two building blocks have a different intracellular fate. These findings provide important insight into the design criteria of artificial organelles with potential structural integrity.     

Hierarchical 3D SERS Substrates Fabricated by Integrating Photolithographic Microstructures and Self‐Assembly of Silver Nanoparticles

Most of the surface‐enhanced Raman scattering (SERS) substrates are 2D planar systems, which limits the SERS active area to a single Cartesian plane. Here, we fabricate 3D SERS substrates with the aim to break the traditional 2D SERS active area limitation, and to extend the SERS hotspots into the third dimension along the z‐axis. Our 3D SERS substrates are tailored with increased SERS hotspots in the z‐direction from tens of nanometers to tens of micrometers, increasing the hotspots in the z‐direction by at least an order of magnitude larger than the confocal volume (～1 μm) of most Raman spectrometers. Various hierarchical 3D SERS‐active microstructures are fabricated by combining 3D laser photolithography with Langmuir‐Blodgett nanoparticle assembly. 3D laser photolithography creates microstructured platforms required to extend the SERS‐active area into 3D, and the self‐assembly of Ag nanoparticles ensures homogeneous coating of SERS‐active Ag nanoparticles over the entire microstructured platforms. Large‐area 3D Raman imaging demonstrates that homogeneous signals can be collected throughout the entire 3D SERS substrates. We vary the morphology, height, and inclination angles of the 3D microstructures, where the inclination angle is found to exhibit strong influence on the SERS signals. We also demonstrate a potential application of this hierarchical 3D SERS substrate in information tagging, storage and encryption as SERS micro‐barcodes, where multiple micro‐barcodes can be created within a single set of microstructures.