Core-satellite assembly of gold nanoshells on solid gold nanoparticles for a color coding plasmonic nanosensor.

We present core-satellite assemblies comprising a solid gold nanoparticle as the core and hollow decahedral gold nanoshells as satellites for tuning the optical properties of the plasmonic structure for sensing. The core-satellite assemblies were fabricated on a substrate via the layer-by-layer assembly of nanoparticles linked by DNA. We used finite-difference time-domain simulations to help guide the geometrical design, and characterized the optical properties and morphology of the solid-shell nanoparticle assemblies using darkfield microscopy, single-nanostructure spectroscopy, and scanning electron microscopy. Plasmon coupling yielded resonant peaks at longer wavelengths in the red to near-infrared range for solid-shell assemblies compared with solid-solid nanoparticle assemblies. We examined sensing with the solid-shell assemblies using adenosine triphosphate (ATP) as a model target and ATP-aptamer as the linker. Binding of ATP induced disassembly and led to a decrease in the scattering intensity and a color change from red to green. The new morphology of the core-satellite assembly enabled plasmonic color-coding of multiplexed sensors. We demonstrate this potential by fabricating two types of assemblies using DNA linkers that target different molecules - ATP and a model nucleic acid. Our work expands the capability of chip-based plasmonic nanoparticle assemblies for the analysis of multiple, different types of biomolecules in small sample sizes including the microenvironment and single cells.

Sensing Biomarkers with Plasmonics.

The detection of biomarkers is critical for enabling early disease diagnosis, monitoring the progression, and tracking the effectiveness of therapeutic intervention. Plasmonic sensors exhibit a broad range of analytical capabilities, from the rapid generation of colorimetric readouts to single-molecule sensitivity in ultralow sample volumes, which have led to their increased exploration in bioanalysis and point-of-care applications. This perspective presents selected accounts of recent developments on the different types of plasmonic sensing platforms, the pervasive challenges, and outlook on the pathway to translation. We highlight the sensing of upcoming biomarkers, including microRNA, circulating tumor cells, exosomes, and cell-free DNA, and discuss the opportunity of utilizing plasmonic nanomaterials and tools for biomarker detection beyond biofluids, such as in tissues, organs, and disease sites. The integration of plasmonic biosensors with established and upcoming technologies of instrumentation, sample pretreatment, and data analysis will help realize their translation to clinical settings for improving healthcare and enhancing the quality of life.

Metabolic mapping with plasmonic nanoparticle assemblies.

A rapid and simple methodology for the biomolecular analysis of single cells and microenvironments via a stick-and-peel plasmonic sensing platform is reported. Substrate-bound assemblies of plasmonic gold nanoparticles linked by reconfigurable oligonucleotides undergo disassembly upon target binding. Changes in the light scattering intensity of thousands of discrete nanoparticle assemblies are extrapolated concomitantly to yield the mapping of local target concentrations. The methodology is completely free of labelling, purification and separation steps. We quantified the intracellular ATP levels for two ovarian cancer cell lines to elucidate the differences and cellular distribution, and demonstrated the potential of the stick-and-peel platform for mapping the microenvironment of a 2D heterogeneous surface. The portable and economical analytical platform may broaden the affordability and applicability of single-cell based analyses and enable new opportunities in clinical care such as on-site molecular pathology.

DNA-Conjugated Gold Nanoparticles as High-Mass Probes in Imaging Mass Cytometry.

We employ imaging mass cytometry (IMC) to investigate in vitro uptake and cellular distribution of DNA-functionalized gold nanoparticles (AuNPs). IMC enables the multiparametric imaging of cell components and allows for the detection of AuNPs in cells with >100 times higher sensitivity than conventional confocal fluorescence imaging, as each nanoparticle contains thousands of atoms for signal amplification. Changes in the accumulation of nanoparticles in cells due to oligonucleotide sequence-dependent interactions are exploited to examine a model biomarker for hypoxia-microRNA-210. We find that AuNPs functionalized with microRNA-210-targeting sequence accumulate in hypoxic cells 3 to 4-fold compared to normoxic cells. The work examines the potential use of DNA-AuNP as high-mass probes for the analysis of nonabundant nucleic acids.

LSPR Tuning from 470 to 800 nm and Improved Stability of Au-Ag Nanoparticles Formed by Gold Deposition and Rebuilding in the Presence of Poly(styrenesulfonate).

Stability and precise control over functional properties of metal nanoparticles remain a challenge for the realization of prospective applications. Our described process of shell formation and rebuilding can address both these challenges. Template silver nanoparticles (AgNPs) stabilized by poly(styrenesulfonate) are first transformed with gold deposition, after which the resulting shell rebuilds with the replaced silver. The shell formation and rebuilding are accompanied by large shifts in localized surface plasmon resonance (LSPR) peak position, which enables LSPR tuning in a range from 470 to 800 nm. Furthermore, chemical stability of Au-AgNPs is significantly improved compared to AgNPs due to gold stability. Silver templates of different shapes and sizes were demonstrated to transform to AuAg composite NPs to further extend the accessible LSPR range tuning. Stabilization of template AgNPs with poly(styrenesulfonate), in contrast to commonly used poly(vinylpyrrolidone), was found to be a key factor for shell rebuilding. The developed Au-AgNPs were shown to be advantageous for surface plasmon resonance (SPR) detection and surface-enhanced Raman spectroscopy (SERS) owing to their tunable LSPR and enhanced stability.

Tuning the Sensing Performance of Multilayer Plasmonic Core-Satellite Assemblies for Rapid Detection of Targets from Lysed Cells.

Optical sensors based on discrete plasmonic nanostructures are invaluable for probing biomolecular interactions when applied as plasmonic rulers or reconfigurable multinanoparticle assemblies. However, their adaptation as a versatile sensing platform is limited by the research-grade instrumentation required for single-nanostructure imaging and/or spectroscopy and complex data fitting and analysis. Additionally, the dynamic range is often too narrow for the quantitative analysis of targets of interest in biodiagnostics, food safety, or environmental monitoring. Herein we present plasmonic assembly comprising a core nanoparticle surrounded by multiple layers of satellite nanoparticles through aptamer linker. The layer-by-layer assembly of the satellite nanoparticles yields uniform discrete nanoparticle clusters on a substrate with enhanced optical properties. Binding of the model target (adenosine 5'-triphosphate, ATP) induces disassembly and leads to a dramatic decrease in the scattering intensity that can be analyzed readily from darkfield images. We demonstrate that the sensing performance, such as detection limit, dynamic range, and sensitivity, can be tuned by controlling the size of the assembly. The substrate-anchored nanoparticle assemblies are selective to only ATP, and not other adenine-containing compounds. By adapting the methodology to a flexible support, cellular ATP can be directly detected by lysing adherent cells in close contact with the plasmonic assemblies-a process that does not require any sample preparation or purification. Enhancing the optical detection signal via designing and engineering nanoparticle assemblies could enable their use with low-cost portable imaging systems and broaden their applicability beyond the study of biomolecular interaction.

Electrical Detection of Quantum Dot Hot Electrons Generated via a Mn2+-Enhanced Auger Process.

An all-solid-state quantum-dot-based photon-to-current conversion device is demonstrated that selectively detects the generation of hot electrons. Photoexcitation of Mn2+-doped CdS quantum dots embedded in the device is followed by efficient picosecond energy transfer to Mn2+ with a long-lived (millisecond) excited-state lifetime. Electrons injected into the QDs under applied bias then capture this energy via Auger de-excitation, generating hot electrons that possess sufficient energy to escape over a ZnS blocking layer, thereby producing current. This electrically detected hot-electron generation is correlated with a quench in the steady-state Mn2+ luminescence and the introduction of a new nonradiative excited-state decay process, consistent with electron-dopant Auger cross-relaxation. The device's efficiency at detecting hot-electron generation provides a model platform for the study of hot-electron ionization relevant to the development of novel photodetectors and alternative energy-conversion devices.

Factors influencing polyelectrolyte-aptamer multilayered films with target-controlled permeability for sensing applications.

Portable, easy-to-use and cost-effective sensing devices are desirable in healthcare, environmental monitoring and food safety. Herein we employ polyelectrolyte-aptamer (PE-aptamer) multilayered films that exhibit target-responsive permeability for colorimetric and electrochemical sensing. We present the quantitative detection of an exemplary small molecule, quinine, and address the potential for detection in complex media by examining interference effects. We optimize the film composition and investigate the importance of the structural-switching ability of the aptamer. The results from both platforms are corroborated to provide an outlook on the applicability of the PE-aptamer film for sensing. The label-free detection combined with the readily adaptive assembly process could be invaluable for diverse analytical fields.

Direct detection of microRNA based on plasmon hybridization of nanoparticle dimers.

MicroRNAs (miRNA) are important for regulating a range of biochemical pathways. Abnormal levels of miRNA in cells or secreted into biological fluids have been identified in diseases. MiRNA can therefore be potential biomarkers for early disease diagnosis; however their detection and quantification are challenging. Herein we apply the sensing platform of discrete actuatable dimers for the detection of human miR-210 (hsa-miR-210-3p). The detection signal is a spectral blue shift in the hybridized plasmon mode as monitored by single-nanostructure spectroscopy. We investigate the specificity and detection limit of the platform and quantify miR-210 levels in RNA extracts of cells cultured under different oxygen tensions. In addition we demonstrate the feasibility of detection in complex media by examining miR-210 secreted in cell media. This sensing platform may be developed as a bioanalytical tool for validating miRNA profiles of biological fluids.

Morphology-based plasmonic nanoparticle sensors: controlling etching kinetics with target-responsive permeability gate.

We present a sensing platform based on the morphological changes of plasmonic nanoparticles. Detection is achieved by using a stimulus-responsive polyelectrolyte-aptamer thin film to control the rate of diffusion of etchants that alter the shape and size of the nanoparticles. We show that the extent of morphological change and the colorimetric response depends on the amount of analyte bound. Contrary to conventional plasmonic sensors, our detection scheme does not rely on any interparticle interaction and is completely label-free, both in terms of the analyte and the capture probe. It presents new opportunities for designing facile, low-cost, and portable chip-based sensors for biodiagnostic and field analysis.

Photoisomerization quantum yield of azobenzene-modified DNA depends on local sequence.

Photoswitch-modified DNA is being studied for applications including light-harvesting molecular motors, photocontrolled drug delivery, gene regulation, and optically mediated assembly of plasmonic metal nanoparticles in DNA-hybridization assays. We study the sequence and hybridization dependence of the photoisomerization quantum yield of azobenzene attached to DNA via the popular d-threoninol linkage. Compared to free azobenzene we find that the quantum yield for photoisomerization from trans to cis form is decreased 3-fold (from 0.094 ± 0.004 to 0.036 ± 0.002) when the azobenzene is incorporated into ssDNA, and is further reduced 15-fold (to 0.0056 ± 0.0008) for azobenzene incorporated into dsDNA. In addition, we find that the quantum yield is sensitive to the local sequence including both specific mismatches and the overall sequence-dependent melting temperature (Tm). These results serve as design rules for efficient photoswitchable DNA sequences tailored for sensing, drug delivery, and energy-harvesting applications, while also providing a foundation for understanding phenomena such as photonically controlled hybridization stringency.

Electron accumulation on metal nanoparticles in plasmon-enhanced organic solar cells.

Plasmonic metal nanoparticles have been used to enhance the performance of thin-film devices such as organic photovoltaics based on polymer/fullerene blends. We show that silver nanoprisms accumulate long-lived negative charges when they are in contact with a photoexcited bulk heterojunction blend composed of poly(3-hexylthiophene)/phenyl-C61-butyric acid methyl ester (P3HT/PCBM). We report both the charge modulation and electroabsorption spectra of silver nanoprisms in solid-state devices and compare these spectra with the photoinduced absorption spectra of P3HT/PCBM blends containing silver nanoprisms. We assign a previously unidentified peak in the photoinduced absorption spectra to the presence of photoinduced electrons on the silver nanoprisms. We show that coating the nanoprisms with a 2.5 nm thick insulating layer can completely inhibit this charging. These results may inform methods for limiting metal-mediated losses in plasmonic solar cells.

Photoswitchable oligonucleotide-modified gold nanoparticles: controlling hybridization stringency with photon dose.

We describe a new class of stimulus-responsive DNA-functionalized gold nanoparticles that incorporate azobenzene-modified oligonucleotides. Beyond the classic directed assembly and sensing behaviors associated with oligonucleotide-modified nanoparticles, these particles also exhibit reversible photoswitching of their assembly behavior. Exposure to UV light induces a trans-cis isomerization of the azobenzene which destabilizes the DNA duplex, resulting in dissociation of the nanoparticle assemblies. The isomerization is reversible upon exposure to blue light, resulting in rehybridization and reassembly of the DNA-linked nanoparticle clusters. We show that perfectly complementary and partially mismatched strands exhibit clearly distinguishable photoinduced melting properties, and we demonstrate that photon dose can thus be used in place of temperature or ionic strength to control hybridization stringency with the ability to discriminate single-base mismatches.

Plasmonic nanoparticle dimers for optical sensing of DNA in complex media.

We introduce a new sensing modality based on the actuation of discrete gold nanoparticle dimers. Binding of the target DNA leads to a geometrical extension of the dimer, thereby yielding a spectral blue shift in the hybridized plasmon mode as detected by single nanostructure scattering spectroscopy. The magnitude and opposite direction of this shift enabled us to spectroscopically distinguish the target from nonspecific binding and to detect the target in complex media like serum.

Synergy of slow photon and chemically amplified photochemistry in platinum nanocluster-loaded inverse titania opals.

We show that the photodegradation efficiency of TiO2 has been amplified 4-fold via the cooperativity of slow photons in photonic crystal and the incorporation of Pt nanoclusters. Various loadings of Pt nanoparticles were photodeposited on the surface of TiO2 inverse opals and the photodegradation of adsorbed acid orange was investigated. While slow photons increased the effective path length of light, Pt nanoparticles extended the lifetimes of the UV-excited electrons and holes. With 2-4 wt % of Pt on the TiO2 inverse opal, we demonstrate a synergistic optical and chemical enhancement for the first time.

Effect of disorder on the optically amplified photocatalytic efficiency of titania inverse opals.

Optically amplified photochemistry with slow photons has been realized in our previous work when a photoactive material such as TiO(2) was molded into a photonic crystal and the corresponding energy of photonic bands overlapped with the electronic excitation. While numerous applications of photonic crystals have been proposed, the real practicality depends on the extent of structural imperfection that can be tolerated before significant deterioration in the optical response deems it unrealistic to use. As a result, it is important to evaluate the amount of structural disorder that can be tolerated in inverse TiO(2) opals if they are to be used as amplified photocatalysts for photolytic degradation of organics in environmental remediation and water purification. We present a systematic study on the effect of disorder with relation to the photocatalytic efficiency of oxidizing methylene blue dye adsorbed on inverse TiO(2) opals by introducing different fractions and sizes of guest spheres into the opal template. Our results show that half of the enhancement originally achieved by the inverse opal made from monodispersed 150-nm spheres is conserved when the domain size of the host spheres remains above a critical threshold. The substitution fraction can be as high as 0.4 when the guest spheres are 1.2 times larger than the host spheres. Such a high tolerance to structural disorder provides strong support for the potential use of inverse TiO(2) opals in environmental cleanup and water treatment applications.

Block copolymers under periodic, strong three-dimensional confinement.

In this communication we study the influence of strong 3D confinement on the self-assembly of diblock copolymers containing a polyferrocenylsilane metallopolymer segment. Both silica colloidal crystals and silica inverse colloidal crystals, having nanometer-scale interconnected pore networks, are used as molds to direct the self-assembly. Unusual morphologies, such as concentric shells and branched lamellae, result from the interaction of the polymer with the high surface area topologically periodic templates.