Nanoplasmonic Particles Research Articles

Brochosome-Inspired Metal-Containing Particles as Biomimetic Building Blocks for Nanoplasmonics: Conceptual Generalizations.

Recently, biological nanostructures became an important source of inspiration for plasmonics, with many described implementations and proposed applications. Among them are brochosome-inspired plasmonic microstructures—roughly spherical core-shell particles with submicrometer diameters and with indented surfaces. Our intention was to start from the nanoplasmonic point of view and to systematically classify possible alternative forms of brochosome-inspired metal-containing particles producible by the state-of-the-art nanofabrication. A wealth of novel structures arises from this systematization of bioinspired metal-containing nanocomposites. Besides various surface nanoapertures, we consider structures closely related to them in electromagnetic sense like surface nano-protrusions, shell reliefs obtained by nano-sculpting, and various combinations of these. This approach helped us build a new design toolbox for brochosome-inspired structures. Additionally, we used the finite elements method to simulate the optical properties of simple brochosome-inspired structures. We encountered a plethora of advantageous optical traits, including enhanced absorption, antireflective properties, and metamaterial behavior (effective refractive index close to zero or negative). We conclude that the presented approach offers a wealth of traits useful for practical applications. The described research represents our attempt to outline a possible roadmap for further development of bioinspired nanoplasmonic particles and to offer a source of ideas and directions for future research.

Nanoplasmonic Sensor Approaches for Sensitive Detection of Disease-Associated Exosomes.

Exosomes are abundantly secreted by most cells that carry membrane and cytosolic factors that can reflect the physiologic state of their source cells and thus have strong potential to serve as biomarkers for early diagnosis, disease staging, and treatment monitoring. However, traditional diagnostic or prognostic applications that might use exosomes are hindered by the lack of rapid and sensitive assays that can exploit their biological information. An array of assay approaches have been developed to address this deficit, including those that integrate immunoassays with nanoplasmonic sensors to measure changes in optical refractive indexes in response to the binding of low concentrations of their targeted molecules. These sensors take advantage of enhanced and tunable interactions between the electron clouds of nanoplasmonic particles and structures and incident electromagnetic radiation to enable isolation-free and ultrasensitive quantification of disease-associated exosome biomarkers present in complex biological samples. These unique advantages make nanoplasmonic sensing one of the most competitive approaches available for clinical applications and point-of-care tests that evaluate exosome-based biomarkers. This review will briefly summarize the origin and clinical utility of exosomes and the limitations of current isolation and analysis approaches before reviewing the specific advantages and limitations of nanoplasmonic sensing devices and indicating what additional developments are necessary to allow the translation of these approaches into clinical applications.

Gold nanoplasmonic particles in tunable porous silicon 3D scaffolds for ultra-low concentration detection by SERS.

A composite material of plasmonic nanoparticles embedded in a scaffold of nano-porous silicon offers unmatched capabilities for use as a SERS substrate. The marriage of these components presents an exclusive combination of tightly focused amplification of Localised Surface Plasmon (LSP) fields inside the material with an extremely high surface-to-volume ratio. This provides favourable conditions for a single molecule or extremely low concentration detection by SERS. In this work the advantage of the composite is demonstrated by SERS detection of Methylene Blue at a concentration as low as a few picomolars. We systematically investigate the plasmonic properties of the material by imaging its morphology, establishing its composition and the effect on the LSP resonance optical spectra.

Dual Mode Rapid Plasmonic Detections of Chemical Disinfectants (CMIT/MIT) Using Target-Mediated Selective Aggregation of Gold Nanoparticles.

Chemical disinfectants such as 5-chloro-2-methylisothiazol-3(2H)-one/2-methyl-4-isothiazolin-3-one (CMIT/MIT) have been widely used in commercial products and humidifiers to prevent the growth of microorganisms. However, as continuous inhalation of CMIT/MIT is a fatal health risk, the concentration of its commercially available form is strictly regulated. Nonetheless, there are limited reports on effective methods for the quick and easy detection of CMIT/MIT. In this study, we have demonstrated rapid and convenient plasmonic methods for the dual-mode detection of CMIT/MIT using gold nanoplasmonic particles (GNPs) and understood the underlying molecular mechanism via additional analyses with microscopic and spectroscopic tools. In the presence of CMIT/MIT, the GNPs can rapidly aggregate due to molecular specific interactions with their capping agents and resultant reaction products. This target-mediated aggregation of the GNPs is represented by a visible color change of the solution from red to purple within just 3 min. By adjusting the reaction ratio between the CMIT/MIT and the GNPs, we could observe a marked color change at the regulation level (15 ppm) with naked eyes without any instruments. In addition, the concentration-dependent Raman spectral change in the reaction solution allows us to crosscheck the observed colorimetric responses both quantitatively and qualitatively based on molecular fingerprint spectra. Therefore, our detection protocol provides a powerful way to develop a high-throughput screening method to ensure that the level of the CMIT/MIT ingredients remains within the regulatory concentration.

On-chip plasmonic immunoassay based on targeted assembly of gold nanoplasmonic particles.

Developing a sensitive and selective detection platform of disease-related biomarkers is important for the diagnosis and treatment of diseases at an early stage. Among clinically meaningful biomarkers, proteins are the most commonly used indicators, and they are generally detected via immunoassays. However, the use of conventional immunoassays in early diagnosis is hindered by the time required, complex steps, high-cost, and insufficient sensitivity and selectivity. Herein, we developed a novel on-chip immunoassay with degassing-driven microfluidic devices and gold nanoplasmonic particles (GNPs). To recognize target proteins, antibody-conjugated GNPs as probes were used in the assay owing to their excellent scattering properties. Using the proposed nonenzymatic immunoassay, we detected amyloid β (Aβ) and Tau proteins, representative biomarkers of Alzheimer's disease, in femtomolar levels. Selective and quantitative detection of Aβ spiked in blood plasma was also achieved for further clinical application of the proposed immunoassay. The proposed plasmonic immunoassay integrated with degassing-driven microfluidic chips provides a new platform for biological assays and diagnosis.

Plasmonic Hybrid Biocomposite as an Effective Substrate for Detection of Biomolecules by Surface-Enhanced Raman Spectroscopy

The enhancement of the Raman light scattering signal from the surface of the porous hybrid biocomposites based on polyhydroxybutyrate (PHB), calcium carbonate (CaCO3), and nanoplasmonic Ag particles is investigated. Based on PHB, fibrous scaffolds are obtained by the electrospinning technique. The fibrous scaffolds have been covered by CaCO3 and Ag nanoparticles by means of mineralization in salt solutions and Ag reduction reaction. Successful formation of the CaCO3 and Ag nanoparticles on the scaffold surface has been confirmed by the data of scanning electron microscopy, x-ray diffraction analysis, and infrared spectroscopy. Surface-enhanced Raman spectroscopy (SERS) of the obtained sample surface has demonstrated a significant enhancement of the Rhodamine 6G signal (Ef > 105) in comparison with the reference sample where the analyte concentration and the laser power were 100 times higher. Thus, the present research has confirmed prospects for the application of biocomposites based on polyhydroxybutyrate for detection and investigation of biomolecules by the SERS method.

Optical nanoscopy with contact Mie-particles: Resolution analysis

The theoretical limits of resolution available in microspherical nanoscopy are explored using incoherent point emitters in the air. The images are calculated using a two-dimensional model and solving the Maxwell equations which account for the wave effects on the sub-wavelength scale of the emitter-microsphere interaction. Based on our results, we propose to use small dielectric particles with diameters λ ≲ D ≲ 2λ made of a high-refractive-index material n∼2 for imaging sub-wavelength objects. It is shown that such particles form virtual images below and real images above them. At wavelengths of the Mie resonances, these images have slightly better than ∼λ/4 resolution that can be attributed to the image magnification in close proximity to the object and contributions of its near field. The resonant super-resolution imaging of various point-like objects, such as dye molecules, fluorophores, or nanoplasmonic particles, can be realized by using narrow bandpass optical filters spectrally aligned with the Mie resonances.

Rapid and high-throughput colorimetric screening for anti-aggregation reagents of protein conformational diseases by using gold nanoplasmonic particles

Cellular deposition of destabilized proteins and their aggregates is considered one of the most indisputable factors implicated in protein conformational diseases. Here, we report an innovative high-throughput screening method for discovering anti-aggregation reagents out of numerous potential candidates by using gold nanoplasmonic particles. In our method, nanoparticles act as catalytic activators to accelerate protein aggregation and simultaneously exhibit a colorimetric response according to their embedded shape on the protein aggregates. Using this principle, we observed the colorimetric response to the anti-aggregation effect of amyloid β (Aβ) with the naked eye within a few minutes. Investigation of the anti-aggregation effects of select candidates under three different protein aggregation stages showed that the anti-aggregation efficiency could relate to disease progression. Finally, results obtained with spiked samples in cerebrospinal fluid as well as under various denaturation conditions and different Aβ compositions show the feasibility of future personalized medicine considering individual patient's disease progression.

Ultrafast colorimetric determination of predominant protein structure evolution with gold nanoplasmonic particles.

The intracellular and extracellular accumulation of disordered proteins and aggregated proteins occurs in many protein conformational diseases, such as aging-related neurodegeneration and alcoholic liver diseases. However, the conventional methods to study protein structural changes are limited for the rapid detection and monitoring of protein aggregation because of long incubation times (i.e., usually several days), complicated sample pretreatment steps, and expensive instrumentation. Here, we describe an ultrafast colorimetric method for the real-time monitoring of protein structure evolution and the determination of predominant structures via nanoparticle-assisted protein aggregation. During the aggregation process, nanoparticles act as nucleation cores, which form networks depending on the structures of the protein aggregates, and accelerate the kinetics of the protein aggregation. Simultaneously, these nanoparticles exhibit colorimetric responses according to their embedded shapes (e.g., fibrillar and amorphous) on the protein aggregates. We observed distinct spectral shifts and concomitant colorimetric responses of concentration- and type-dependent protein aggregation with the naked eye within a few minutes (<2 min) under acidic conditions. Moreover, the morphological transitions from small aggregates to larger aggregates of nanoparticle-assisted protein aggregates were visualized with dark-field microscope imaging, which show a similar trend with that of protein aggregates formed without the aid of nanoparticles. Finally we show that our proposed method can be utilized to screen the protein aggregation propensity under a variety of conditions such as different pH levels, high temperature, and chemicals. These findings suggest that the proposed method is an easy way to study the molecular biophysics of protein aggregation and to rapidly screen anti-aggregation drugs for protein conformational diseases.

Femtosecond pulse shaping by ultrathin plasmonic metasurfaces

In this work, a compact and ultrathin plasmonic metasurface is proposed for an ultrashort pulse shaping method in the optical regime based on linear filtering principles. A planar array of nanoplasmonic particles is employed to manipulate the transmission spectrum of propagating ultrashort pulses to shape its temporal characteristics. We demonstrate that the method is able to broaden, compress, and reshape the polarization of ultrashort pulses with great control over its characteristics by engineering the resonances of the ultrathin plasmonic metasurface.

A sensitive colorimetric strategy for monitoring cerebral β-amyloid peptides in AD based on dual-functionalized gold nanoplasmonic particles.

A sensitive and selective strategy for the colorimetric visualization of the total monomeric Aβ down to 40 pg mL(-1) based on dual-functionalized gold nanoplasmonic particles (GNPs) is developed and applied to evaluate Aβ levels in the AD cerebral system.

Rapid Detection of Protein Aggregation and Inhibition by Dual Functions of Gold Nanoplasmonic Particles: Catalytic Activator and Optical Reporter

Neurodegenerative diseases share common molecular mechanisms in disease pathogenesis: protein misfolding and abnormal aggregation. Current detection methods of protein aggregations require time-consuming and labor-intensive steps, which delay the process of drug discovery and understanding the mechanism of protein aggregation. Here, we present a rapid detection method for studying protein aggregation and inhibition under a variety of perturbation conditions by dual functions of gold nanoplasmonic particles (GNPs): catalytic activator and optical reporter. As a proof-of-concept demonstration, we employed the acidic perturbation permitting rapid cooperative assemblies of GNPs and amyloid-β (Aβ) peptides (implicated in Alzheimer's disease) via their surface charge modulation. Because of roles of GNPs as effective nucleation sites for fast-catalyzing protein aggregation and colorimetric optical reporters for tracking protein aggregation, we accomplished the fast aggregation assay in less than 1 min by the naked eyes. Under the given acidic perturbation condition, we characterized the concentration-dependent colorimetric responses for aggregation at physiologically relevant Aβ concentration levels without any instrumentation. We also demonstrated the GNP/acidic condition-based rapid inhibition assay of Aβ aggregation by using well-known binding reagents such as antibody and serum albumin. Consistent results were also obtained from the tests with superoxide dismutase protein implicated in Lou Gehrig's disease. The proposed methodology can be a powerful alternative method for screening drugs for neurodegenerative disease as well as studying molecular biophysics of protein aggregations, and further extended to explore other protein conformational diseases.

Colorimetric detection of microRNA miR-21 based on nanoplasmonic core–satellite assembly

In order to detect microRNAs (miRNAs), we developed a colorimetric sensing method on the basis of the plasmonic coupling effect. Gold nanoplasmonic particles (GNPs) are assembled in a core-satellite configuration in the presence of target miRNA, inducing remarkable changes in the scattering color and spectra at the picomolar level with selectivity.

Rapid Detection of Aβ Aggregation and Inhibition by Dual Functions of Gold Nanoplasmic Particles: Catalytic Activator and Optical Reporter

One of the primary pathological hallmarks of Alzheimer's diseases (AD) is amyloid-β (Aβ) aggregation and its extracellular accumulation. However, current in vitro Aβ aggregation assays require time-consuming and labor-intensive steps, which delay the process of drug discovery and understanding the mechanism of Aβ induced neurotoxicity. Here, we propose a rapid detection method for studying Aβ aggregation and inhibition under an optimized acidic perturbation condition by dual functions of gold nanoplasmonic particles (GNPs): (1) catalytic activator and (2) optical reporter. Because of roles of GNPs as effective nucleation sites for fast-catalyzing Aβ aggregation and colorimetric optical reporters for tracking Aβ aggregation, we accomplished the fast aggregation assay in less than 1 min by the naked eyes. Our detection method is based on spontaneous clustering of unconjugated (unmodified) GNPs along with the aggregated Aβ network under an aggregation-promoting condition. As a proof-of-concept demonstration, we employed the acidic perturbation permitting rapid cooperative assemblies of GNPs and Aβ peptides via their surface charge modulation. Under the optimized acidic perturbation condition around pH 2 to 3, we characterized the concentration-dependent colorimetric responses for aggregation at physiologically relevant Aβ concentration levels (from 100 μM to 10 nM). We also demonstrated the GNP/acidic condition-based rapid inhibition assay of Aβ aggregation by using well-known binding reagents such as antibody and serum albumin. The proposed methodology can be a powerful alternative method for screening drugs for AD as well as studying molecular biophysics of protein aggregations, and further extended to explore other protein conformational diseases such as neurodegenerative disease.

Abstract 2721: Real-time and label-free aptasensor of VEGF for cancer diagnostics

Abstract Early detection of cancer markers is a critical demand for clinical research, particularly in preventing cancer cells from establishing themselves in a metastatic stage. We have developed a stable, sensitive, and selective detection method utilizing a nanoplasmonic ‘aptasensor’ (aptamer-based sensor) of vascular endothelial growth factor (VEGF) for breast cancer diagnostics. Nanoplasmonic aptasensors are prepared by fixing gold nanoplasmonic particles (GNPs) on an amino-silane coated glass slide and coating poly-L-lysine (PLL) on top of GNPs, which provides the GNP with a strong positive-charged surface and a spacing layer avoiding quenching. To accomplish high selectivity, VEGF-specific aptamers are immobilized on the PLL-GNP surface by an electrostatic force. To monitor the event of target binding, the aptamer is conjugated with a fluorescent molecule, Cy-3, which has an absorption peak wavelength (λ = 552 nm) that matches with a localized surface plasmon resonance wavelength of the 80 nm in diameter GNP (λ ≈ 550 nm). In the absence of target VEGF molecules, Cy-3 is spaced in a relevant coupling distance from the GNP surface for the surface plasmon resonance to amplify an incident light and enhance the fluorescent signal of Cy-3. However, once VEGF molecules bind to the aptamer-Cy-3, the conformational change of aptamer occurs, leading to its subsequent detachment from the GNP surface, which results in no signal enhancement and, thus, a loss in the fluorescence intensity. Therefore, the concentration of VEGF molecules can be estimated by measuring the amount of signal decrease in the fluorescence intensity. With high affinity and specificity, the aptasensor of VEGF requires a small amount of sample (10 μL) for a single detection and incubation time of 1 hour at a room temperature. Also, the aptasensor achieves VEGF detection from 100 nM (2 μg/mL) to 100 pM (2 ng/mL) with a signal decrease up to 50%. In contrast, there is no discernible signal change in a non-specific binding protein solution (100 nM bovine serum albumin) or a strong ionic solution (1.4 M NaCl). Furthermore, the aptasensor is applicable to VEGF detection in human fluids, owing to the biological stability of a fully 2′-O-methyl nucleotide-based aptamer. We can detect VEGF molecules present in saliva and serum of breast cancer patients by observing signal decrease corresponding to the concentration of 100 nM (2 μg/mL) VEGF and a consistent decrease with concentration variation from 1 to 100 % in saline. The aptamer-based nanoplasmonic sensor may be useful for not only basic studies on angiogenesis but also clinical research in evaluating the effectiveness of drug candidates that inhibit VEGF secretion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2721.

Nanoplasmonic-Particle-Enhanced Optical Molecular Sensing

Metallic nanoparticles have a strong localized plasmon resonance that is influenced by the physical properties of the nanoparticles and their immediate ambient environment. Electromagnetic field and plasmon energy can also be manipulated by engineering nanoparticle plasmonic structures to concentrate and transport the electromagnetic energy, as well as by transferring the plasmon energy. If coupled with chemical and biological molecules on the surfaces, nanoplasmonic particles and related structures can be used to detect and measure static and dynamic molecular interactions <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in intro</i> and <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> . The nanoplasmonic particle molecular sensor is an emerging research tool to help in answering questions of sophisticated genetic processing and cellular signaling mechanisms, as well as early diagnostic imaging of human diseases. The optical molecular sensing enhanced by plasmonic nanoparticles is discussed in the aspects of fundamental theories, nanofabrication, optical spectroscopy, and imaging. Many biomedical applications are also reviewed.

Remote optical switch for localized and selective control of gene interference.

Near infrared-absorbing gold nanoplasmonic particles (GNPs) are used as optical switches of gene interference and are remotely controlled using light. We have tuned optical switches to a wavelength where cellular photodamage is minimized. Optical switches are functionalized with double-stranded oligonucleotides. At desired times and at specific intracellular locations, remote optical excitation is used to liberate gene-interfering oligonucleotides. We demonstrate a novel gene-interfering technique offering spatial and temporal control, which is otherwise impossible using conventional gene-interfering techniques.