Enhanced Molecular Interaction of 3D Plasmonic Nanoporous Gold Alloys by Electronic Modulation for Sensitive Molecular Detection.

Three-dimensional gold and its alloyed nanoporous structures possess high surface areas and strong local electric fields, rendering them ideal substrates for plasmonic molecular detection. Despite enhancing plasmonic properties and altering molecular interactions, the effect of alloy composition on molecular detection capability has not yet been explored. Here, we report molecular interactions between nanoporous gold alloys and charged molecules by controlling the alloy composition. We demonstrate enhanced adsorption of negatively charged molecules onto the alloy surface due to positively charged gold atoms and a shifted d-band center through charge transfer between gold and other metals. Despite similar EM field intensities, nanoporous gold with silver (Au/Ag) achieves SERS enhancement factors (EF) up to 6 orders of magnitude higher than those of other alloys for negatively charged molecules. Finally, nanoporous Au/Ag detects amyloid-beta at concentrations as low as approximately 1 fM, with SERS EF up to 10 orders of magnitude higher than that of a monolayer of Au nanoparticles.

Capillarity-Driven Enrichment and Hydrodynamic Trapping of Trace Nucleic Acids by Plasmonic Cavity Membrane for Rapid and Sensitive Detections.

Small-reactor-based polymerase chain reaction (PCR) has attracted considerable attention. A significant number of tiny reactors must be prepared in parallel to capture, amplify, and accurately quantify few target genes in clinically relevant large volume, which, however, requires sophisticated microfabrication and longer sample-to-answer time. Here, single plasmonic cavity membrane is reported that not only enriches and captures few nucleic acids by taking advantage of both capillarity and hydrodynamic trapping but also quickly amplifies them for sensitive plasmonic detection. The plasmonic cavity membrane with few nanoliters in a void volume is fabricated by self-assembling gold nanorods with SiO2 tips. Simulations reveal that hydrodynamic stagnation between the SiO2 tips is mainly responsible for the trapping of the nucleic acid in the membrane. Finally, it is shown that the plasmonic cavity membrane is capable of enriching severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes up to 20 000-fold within 1 min, amplifying within 3 min, and detecting the trace genes as low as a single copy µL-1. It is anticipated that this work not only expands the utility of PCR but also provides an innovative way of the enrichment and detection of trace biomolecules in a variety of point-of-care testing applications.

Electron-Transport-Chain-Mediated Selective Growth of Gold Nanocrystals in the Intermembrane Space of Live Microbial Cells.

Hybridization of microbial cells with inorganic nanoparticles that could dramatically improve cellular functions such as electron transfer has been realized by the random attachment or stochastic entry of the nanoparticles. Clearly, the selective growth of inorganic nanoparticles on target functional organelles is ideal for such hybridization. Here, we report the selective growth of gold nanocrystals in the intermembrane space (IMS) of Escherichia coli by exploiting the electron transport chain (ETC). We systematically show that gold ions are permeated through porins in the outer membrane of E. coli and further reduced to gold nanocrystals by the ETC in live E. coli. We directly observe that the resulting gold nanocrystals exist only in the IMS by transmission electron microscopy measurements of cross-sectioned E. coli. Molecular dynamics simulations suggest that once gold ions are reduced to small nuclei by the ETC, the nuclei can be stably physisorbed onto ETC complexes, further supporting the ETC-mediated growth. Finally, we show that the ATP synthesis of E. coli where gold nanocrystals are formed in the IMS is up to 9 times higher than that of E. coli alone. We believe that our work can significantly contribute to not only improving microbial metabolic functions for biological energy conversion but also restoring physiological dysfunctions of microbial cells for biomedicine.

Plasmonic Optical Wells-Based Enhanced Rate PCR.

Rapid, sensitive, inexpensive point-of-care molecular diagnostics are crucial for the efficient control of spreading viral diseases and biosecurity of global health. However, the gold standard, polymerase chain reaction (PCR) is time-consuming and expensive and needs specialized testing laboratories. Here, we report a low-cost yet fast, selective, and sensitive Plasmonic Optical Wells-Based Enhanced Rate PCR: POWER-PCR. We optimized the efficient optofluidic design of 3D plasmonic optical wells via the computational simulation of light-to-heat conversion and thermophoretic convection in a self-created plasmonic cavity. The POWER-PCR chamber with a self-passivation layer can concentrate incident light to accumulate molecules, generate rapid heat transfer and thermophoretic flow, and minimize the quenching effect on the naked Au surface. Notably, we achieved swift photothermal cycling of nucleic acid amplification in POWER-PCR on-a-chip in 4 min 24 s. The POWER-PCR will provide an excellent solution for affordable and sensitive molecular diagnostics for precision medicine and preventive global healthcare.

Bubble-free diatoms polymerase chain reaction.

Polymerase chain reaction (PCR) in small fluidic systems not only improves speed and sensitivity of deoxyribonucleic acid (DNA) amplification but also achieves high-throughput quantitative analyses. However, air bubble trapping and growth during PCR has been considered as a critical problem since it causes the failure of DNA amplification. Here we report bubble-free diatom PCR by exploiting a hierarchically porous silica structure of single-celled algae. We show that femtoliters of PCR solution can be spontaneously loaded into the diatom interior without air bubble trapping due to the surface hydrophilicity and pore structure of the diatom. We discover that a large pressure gradient between air bubbles and nanopores rapidly removes residual air bubbles through the periodically arrayed nanopores during thermal cycling. We demonstrate the DNA amplification by diatom PCR without air bubble trapping and growth. Finally, we successfully detect DNA fragments of SARS-CoV-2 with as low as 10 copies/µl by devising a microfluidic device integrated with diatoms assembly. We believe that our work can be applied to many PCR applications for innovative molecular diagnostics and provides new opportunities for naturally abundant diatoms to create innovative biomaterials in real-world applications.

Colloidal Multiscale Assembly via Photothermally Driven Convective Flow for Sensitive In-Solution Plasmonic Detections.

The assembly of metal nanoparticles and targets to be detected in a small light probe volume is essential for achieving sensitive in-solution surface-enhanced Raman spectroscopy (SERS). Such assemblies generally require either chemical linkers or templates to overcome the random diffusion of the colloids unless the aqueous sample is dried. Here, a facile method is reported to produce 3D multiscale assemblies of various colloids ranging from molecules and nanoparticles to microparticles for sensitive in-solution SERS detection without chemical linkers and templates by exploiting photothermally driven convective flow. The simulations suggest that colloids sub 100 nm in diameter can be assembled by photothermally driven convective flow regardless of density; the assembly of larger colloids up to several micrometers by convective flow is significant only if their density is close to that of water. Consistent with the simulation results, the authors confirm that the photothermally driven convective flow is mainly responsible for the observed coassembly of plasmonic gold nanorods with either smaller molecules or larger microparticles. It is further found that the coassembly with the plasmonic nanoantennae leads to dramatic Raman enhancements of molecules, microplastics, and microbes by up to fivefold of magnitude compared to those measured in solution without the coassembly.

Controlling Equilibrium Morphologies of Bimetallic Nanostructures Using Thermal Dewetting via Phase-Field Modeling.

Herein, we report a computational model for the morphological evolution of bimetallic nanostructures in a thermal dewetting process, with a phase-field framework and superior optical, physical, and chemical properties compared to those of conventional nanostructures. The quantitative analysis of the simulation results revealed nano-cap, nano-ring, and nano-island equilibrium morphologies of the deposited material in thermal dewetting, and the morphologies depended on the gap between the spherical patterns on the substrate, size of the substrate, and deposition thickness. We studied the variations in the equilibrium morphologies of the nanostructures with the changes in the shape of the substrate pattern and the thickness of the deposited material. The method described herein can be used to control the properties of bimetallic nanostructures by altering their equilibrium morphologies using thermal dewetting.

Water-Wettable Open Plasmonic Nanocavities for Ultrasensitive Molecular Detections in Multiple Phases.

Plasmonic nanocavities between metal nanoparticles on metal films are either hydrophobic or fully occupied by nonmetallic spacers, preventing molecular diffusion into electromagnetic hotspots. Here we realize water-wettable open plasmonic cavities by devising gold nanoparticle with site-selectively grown ultrathin dielectric layer-on-gold film structures. We directly confirm that hydrophilic dielectric layers of SiO2 or TiO2, which are formed only at the tips of gold nanorod via precise temperature control, render sub-10 nm cavities open to the surroundings and completely water-wettable. Simulations reveal that spontaneous wetting in our cavities is driven by the presence of tip-selective hydrophilic layer and tendency of minimizing high energy air/water interface inside the cavities. Our plasmonic cavities show significant Raman enhancement of up to 4 orders of magnitude higher than those of conventional ones for molecules in various media. Our findings will offer new opportunities for sensing applications of plasmonic nanocavities and have huge impacts on cavity plasmonics.

Active Surface Hydrophobicity Switching and Dynamic Interfacial Trapping of Microbial Cells by Metal Nanoparticles for Preconcentration and In-Plane Optical Detection.

The surface hydrophobicity of a microbial cell is known to be one of the important factors in its adhesion to an interface. To date, such property has been altered by either genetic modification or external pH, temperature, and nutrient control. Here we report a new strategy to engineer a microbial cell surface and discover the unique dynamic trapping of hydrophilic cells at an air/water interface via hydrophobicity switching. We demonstrate the surface transformation and hydrophobicity switching of Escherichia coli (E. coli) by metal nanoparticles. By employing real-time dark-field imaging, we directly observe that hydrophobic gold nanoparticle-coated E. coli, unlike its naked counterpart, is irreversibly trapped at the air/water interface because of elevated hydrophobicity. We show that our surface transformation method and resulting dynamic interfacial trapping can be generally extended to Gram-positive bateria, Gram-negative bacteria, and fungi. As the dynamic interfacial trapping allows the preconcentration of microbial cells, high intensity of scattering light, in-plane focusing, and near-field enhancement, we are able to directly quantify E. coli as low as 1.0 × 103 cells/ml by using a smartphone with an image analyzer. We also establish the identification of different microbial cells by the characteristic Raman transitions directly measured from the interfacially trapped cells.

Bubble-free rapid microfluidic PCR.

Microfluidic polymerase chain reaction (PCR) has been of great interest owing to its ability to perform rapid and specific nucleic acid amplification and analysis on small volumes of samples. One of the major drawbacks of microfluidic PCR is bubble generation and reagent evaporation, which can cause malfunctions. Here, through theoretical modeling and characterization of bubble behavior, we propose a bubble-free microfluidic PCR device via controlled fluid transfer. Our approach exploits a thin impermeable polyethylene (PE) top layer that minimizes the generation of bubbles by inhibiting mass transport along a vertical direction. Simulation results demonstrate that a calculated mass flow difference of approximately 370% can be obtained by utilizing an impermeable membrane as the vertical barrier layer. To demonstrate proof-of-concept, two nanoporous polymeric materials, poly(dimethylsiloxane) (PDMS) and PE, were used for stand-alone self-powered sample loading (approximately 70 s) and for use as a vertical barrier layer, respectively. Consequently, we demonstrate successful amplification of the cMET gene, a nucleic acid (NA) biomarker for lung cancer, and complete an ultrafast PCR test in less than 3 min using a high powered Peltier-based thermal cycler under bubble-free conditions. This approach will result in a new paradigm for ultrafast molecular diagnosis and can facilitate NA-based nearly instantaneous diagnostics for point-of-care testing and for personalized and preventive medicine.

Plasmonic bacteria on a nanoporous mirror via hydrodynamic trapping for rapid identification of waterborne pathogens.

A rapid, precise method for identifying waterborne pathogens is critically needed for effective disinfection and better treatment. However, conventional methods, such as culture-based counting, generally suffer from slow detection times and low sensitivities. Here, we developed a rapid detection method for tracing waterborne pathogens by an innovative optofluidic platform, a plasmonic bacteria on a nanoporous mirror, that allows effective hydrodynamic cell trapping, enrichment of pathogens, and optical signal amplifications. We designed and simulated the integrated optofluidic platform to maximize the enrichment of the bacteria and to align bacteria on the nanopores and plasmonic mirror via hydrodynamic cell trapping. Gold nanoparticles are self-assembled to form antenna arrays on the surface of bacteria, such as Escherichia coli and Pseudomonas aeruginosa, by replacing citrate with hydroxylamine hydrochloride in order to amplify the signal of the plasmonic optical array. Owing to the synergistic contributions of focused light via the nanopore geometry, self-assembled nanoplasmonic optical antennas on the surface of bacteria, and plasmonic mirror, we obtain a sensitivity of detecting E. coli as low as 102 cells/ml via surface-enhanced Raman spectroscopy. We believe that our label-free strategy via an integrated optofluidic platform will pave the way for the rapid, precise identification of various pathogens.

Photothermal Convection Lithography for Rapid and Direct Assembly of Colloidal Plasmonic Nanoparticles on Generic Substrates.

Controlled assembly of colloidal nanoparticles onto solid substrates generally needs to overcome their thermal diffusion in water. For this purpose, several techniques that are based on chemical bonding, capillary interactions with substrate patterning, optical force, and optofluidic heating of light-absorbing substrates are proposed. However, the direct assembly of colloidal nanoparticles on generic substrates without chemical linkers and substrate patterning still remains challenging. Here, photothermal convection lithography is proposed, which allows the rapid placement of colloidal nanoparticles onto the surface of diverse solid substrates. It is based on local photothermal heating of colloidal nanoparticles by resonant light focusing without substrate heating, which induces convective flow. The convective flow, then, forces the colloidal nanoparticles to assemble at the illumination point of light. The size of the assembly is increased by either increasing the light intensity or illumination time. It is shown that three types of colloidal gold nanoparticles with different shapes (rod, star, and sphere) can be uniformly assembled by the proposed method. Each assembly with a diameter of tens of micrometers can be completed within a minute and its patterned arrays can also be achieved rapidly.

Microphysiological Analysis Platform of Pancreatic Islet ß-Cell Spheroids.

The hallmarks of diabetics are insufficient secretion of insulin and dysregulation of glucagon. It is critical to understand release mechanisms of insulin, glucagon, and other hormones from the islets of Langerhans. In spite of remarkable advancements in diabetes research and practice, robust and reproducible models that can measure pancreatic ß-cell function are lacking. Here, a microphysiological analysis platform (MAP) that allows the uniform 3D spheroid formation of pancreatic ß-cell islets, large-scale morphological phenotyping, and gene expression mapping of chronic glycemia and lipidemia development is reported. The MAP enables the scaffold-free formation of densely packed ß-cell spheroids (i.e., multiple array of 110 bioreactors) surrounded with a perfusion flow network inspired by physiologically relevant microenvironment. The MAP permits dynamic perturbations on the ß-cell spheroids and the precise controls of glycemia and lipidemia, which allow us to confirm that cellular apoptosis in the ß-cell spheroid under hyperglycemia and hyperlipidemia is mostly dependent to a reactive oxygen species-induced caspase-mediated pathway. The ß-cells' MAP might provide a potential new map in the pathophysiological mechanisms of ß cells.

Spontaneous Phase Transfer-Mediated Selective Removal of Heavy Metal Ions Using Biocompatible Oleic Acid.

Here, we propose an environmentally benign removal technique for heavy metal ions based on selective and spontaneous transfer to oleic acid. The ions can be removed via (1) the selective and rapid complexation with the carboxylic end of oleic acid at an oleic acid/water interface, and (2) the diffusion of such complex into the oleic acid layer. A wide variety of heavy metal ions such as Cu2+, Pb2+, Zn2+, and Ni2+ can be selectively removed over K+ and Na+. For example, the concentration of Cu2+ is reduced to below 1.3 ppm within 24 h, which corresponds to the level of Cu2+ permitted by the Environmental Protection Agency. The addition of ethylenediamine ligand to the metal ion solutions is also shown to enhance the phase transfer. The removal efficiency is increased by up to 6 times when compared with that in the absence of the ligand and follows the order, Cu2+ (99%) > Pb2+ (96%) > Zn2+ (95%) > Ni2+ (65%). Moreover, the removal time can be shortened from 24 h to 1 h. The effect of an emulsion induced by a mechanical agitation on the removal of heavy metal ion is also studied.

Monolithic Two-Dimensional Photonic Crystal Reflectors for the Fabrication of Highly Efficient and Highly Transparent Dye-Sensitized Solar Cells.

The transparent characteristic of dye-sensitized solar cells (DSCs) makes them suitable for building integrated photovoltaic (BIPV) devices. However, the diffusive scattering layer, which is usually used to increase the efficiency of these devices, greatly lowers the transparency of the DSC. This paper described a two-dimensional (2D) photonic crystal (PC) reflector with a sub-micrometer characteristic length that can improve the efficiency of these devices while maintaining transparency. This 2D PCs were fabricated directly onto TiO2 photoelectrodes using colloidal lithography and have the structure of a nanopillar array. A nanopillar with a height of 430 nm was observed to selectively reflect up to 40% of the light of 400-500 nm wavelength. The perceived transparency of the 2D PC electrode was 52%, which is much higher than 0.3% of the conventional scattering layer. The DSC fabricated using the 2D PC electrode demonstrated a maximum photon-to-electric conversion efficiency of 8.23%, which is 18% higher than the pristine electrode. The 2D PC is a highly efficient and wavelength-selective reflector that can be applied to various photoelectric conversion devices.

Design of a Porous Cathode for Ultrahigh Performance of a Li-ion Battery: An Overlooked Pore Distribution.

Typical cathode materials of Li-ion battery suffer from a severe loss in specific capacity, and this problem is regarded as a major obstacle in the expansion of newer applications. To overcome this, porous cathodes are being extensively utilized. However, although it seems that the porosity in the cathode would be a panacea for high performance of LIBs, there is a blind point in the cathode consisting of porous structures, which makes the porous design to be a redundant. Here, we report the importance of designing the porosity of a cathode in obtaining ultrahigh performance with the porous design or a degraded performance even with increase of porosity. Numerical simulations show that the cathode with 40% porosity has 98% reduction in the loss of specific capacity when compared to the simple spherical cathode when the C-rate increases from 2.5 to 80 C. In addition, the loss over total cycles decreases from 30% to only about 1% for the cathode with 40% porosity under 40 C. Interestingly, however, the specific capacity could be decreased even with the increase in porosity unless the pores were evenly distributed in the cathode. The present analysis provides an important insight into the design of ultrahigh performance cathodes.

General and programmable synthesis of hybrid liposome/metal nanoparticles.

Hybrid liposome/metal nanoparticles are promising candidate materials for biomedical applications. However, the poor selectivity and low yield of the desired hybrid during synthesis pose a challenge. We designed a programmable liposome by selective encoding of a reducing agent, which allows self-crystallization of metal nanoparticles within the liposome to produce stable liposome/metal nanoparticles alone. We synthesized seven types of liposome/monometallic and more complex liposome/bimetallic hybrids. The resulting nanoparticles are tunable in size and metal composition, and their surface plasmon resonance bands are controllable in visible and near infrared. Owing to outer lipid bilayer, our liposome/Au nanoparticle shows better colloidal stability in biologically relevant solutions as well as higher endocytosis efficiency than gold nanoparticles without the liposome. We used this hybrid in intracellular imaging of living cells via surface-enhanced Raman spectroscopy, taking advantage of its improved physicochemical properties. We believe that our method greatly increases the utility of metal nanoparticles in in vivo applications.

Three-Dimensional Polymeric Mechanical Metamaterials Fabricated by Multibeam Interference Lithography with the Assistance of Plasma Etching.

The pentamode structure is a type of mechanical metamaterial that displays dramatically different bulk and shear modulus responses. In this study, a face-centered cubic (FCC) polymeric microstructure was fabricated by using SU8 negative-type photoresists and multibeam interference exposure. Isotropic plasma etching is used to control the solid-volume fraction; for the first time, we obtained a structure with the minimum solid-volume fraction as low as 15% that still exhibited high structural integrity. Using this method, we reduced the width of atom-to-atom connections by up to 40 nm. We characterize the effect of the connection area on the anisotropy of the mechanical properties using simulations. Nanoindentation measurements were also conducted to evaluate the energy dissipation by varying the connection area. The Young's/shear modulus ratio is 5 times higher for the etched microstructure than that of the bulk SU8 materials. The use of interference lithography may enable the properties of microscale materials to be engineered for various applications, such as MEMS.

Spontaneous Self-Formation of 3D Plasmonic Optical Structures.

Self-formation of colloidal oil droplets in water or water droplets in oil not only has been regarded as fascinating fundamental science but also has been utilized in an enormous number of applications in everyday life. However, the creation of three-dimensional (3D) architectures by a liquid droplet and an immiscible liquid interface has been less investigated than other applications. Here, we report interfacial energy-driven spontaneous self-formation of a 3D plasmonic optical structure at room temperature without an external force. Based on the densities and interfacial energies of two liquids, we simulated the spontaneous formation of a plasmonic optical structure when a water droplet containing metal ions meets an immiscible liquid polydimethylsiloxane (PDMS) interface. At the interface, the metal ions in the droplet are automatically reduced to form an interfacial plasmonic layer as the liquid PDMS cures. The self-formation of both an optical cavity and integrated plasmonic nanostructure significantly enhances the fluorescence by a magnitude of 1000. Our findings will have a huge impact on the development of various photonic and plasmonic materials as well as metamaterials and devices.

Multifunctional hydrogel nano-probes for atomic force microscopy.

Since the invention of the atomic force microscope (AFM) three decades ago, there have been numerous advances in its measurement capabilities. Curiously, throughout these developments, the fundamental nature of the force-sensing probe-the key actuating element-has remained largely unchanged. It is produced by long-established microfabrication etching strategies and typically composed of silicon-based materials. Here, we report a new class of photopolymerizable hydrogel nano-probes that are produced by bottom-up fabrication with compressible replica moulding. The hydrogel probes demonstrate excellent capabilities for AFM imaging and force measurement applications while enabling programmable, multifunctional capabilities based on compositionally adjustable mechanical properties and facile encapsulation of various nanomaterials. Taken together, the simple, fast and affordable manufacturing route and multifunctional capabilities of hydrogel AFM nano-probes highlight the potential of soft matter mechanical transducers in nanotechnology applications. The fabrication scheme can also be readily utilized to prepare hydrogel cantilevers, including in parallel arrays, for nanomechanical sensor devices.