Label-free and liquid state SERS detection of multi-scaled bioanalytes via light-induced pinpoint colloidal assembly.

Surface-enhanced Raman scattering (SERS) has been extensively applied to detect complex analytes due to its ability to enhance the fingerprint signals of molecules around nanostructured metallic surfaces. Thus, it is essential to design SERS-active nanostructures with abundant electromagnetic hotspots in a probed volume according to the dimensions of the analytes, as the analytes must be located in their hotspots for maximum signal enhancement. Herein, we demonstrate a simple method for detecting robust SERS signals from multi-scaled bioanalytes, regardless of their dimensions in the liquid state, through a photothermally driven co-assembly with colloidal plasmonic nanoparticles as signal enhancers. Under resonant light illumination, plasmonic nanoparticles and analytes in the solution quickly assemble at the focused surface area by convective movements induced by the photothermal heating of the plasmonic nanoparticles without any surface modification. Such collective assemblies of plasmonic nanoparticles and analytes were optimized by varying the optical density and surface charge of the nanoparticles, the viscosity of the solvent, and the light illumination time to maximize the SERS signals. Using these light-induced co-assemblies, the intrinsic SERS signals of small biomolecules can be detected down to nanomolar concentrations based on their fingerprint spectra. Furthermore, large-sized biomarkers, such as viruses and exosomes, were successfully detected without labels, and the complexity of the collected spectra was statistically analyzed using t-distributed stochastic neighbor embedding combined with support vector machine (t-SNE + SVM). The proposed method is expected to provide a robust and convenient method to sensitively detect biologically and environmentally relevant analytes at multiple scales in liquid samples.

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.

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.

Controlled drug release with surface-capped mesoporous silica nanoparticles and its label-free in situ Raman monitoring.

Mesoporous silica nanoparticles (MSNs) have drawn attention as efficient nanocarriers for drug delivery systems owing to their unique physiochemical properties. However, systemically controlling the kinetics of drug release from the nanocarriers and in situ monitoring of the drug release are still challenging. Here, we report surface-capped MSNs used for controlled drug release and demonstrate label-free in situ Raman monitoring of released drugs based on the molecule-specific spectral fingerprints. By capping the surface of MSNs with amine moieties, gold nanoparticles, and albumin, we achieved high loading efficiencies (up to 97%) of doxorubicin and precisely controlled drug release stimulated by changing pH value. Moreover, we monitored in real-time drug release profile and visualized cellular distribution of the delivered drug at nanoscale based on its intrinsic Raman peak. Finally, we evaluated drug responses in cancer cells and normal cells to investigate whether capped-dMSNs exhibit selective drug release. Our findings would be beneficial for designing smart drug carriers and directly monitoring the release behavior of drugs in actual cellular environments.

Facile Fabrication of Large-Scale Porous and Flexible Three-Dimensional Plasmonic Networks.

Assembling metallic nanoparticles and trapping target molecules within the probe volume of the incident light are important in plasmonic detection. Porous solid structures with three-dimensionally integrated metal nanoparticles would be very beneficial in achieving these objectives. Currently, porous inorganic oxides are being prepared under stringent conditions and further subjected to either physical or chemical attachment of metal nanoparticles. In this study, we propose a facile method to fabricate large-scale porous and flexible three-dimensional (3D) plasmonic networks. Initially, uncured polydimethylsiloxane (PDMS), in which metal ions are dissolved, diffuses spontaneously into the simple sugar crystal template via capillary action. As PDMS is cured, metal ions are automatically reduced to form a dense array of metal nanoparticles. After curing, the sugar template is easily removed by water treatment to obtain porous 3D plasmonic networks. We controlled the far-field scattering and near-field enhancement of the network by changing either the metal ion precursor or its concentration. To demonstrate the key advantages of our 3D plasmonic networks, such as simple fabrication, optical signal enhancement, and molecular trapping, we conducted sensitive Raman detection of several important molecules, including adenine, humidifier disinfectants, and volatile organic compounds.

Facile Amplification of Solution-State Surface-Enhanced Raman Scattering of Small Molecules Using Spontaneously Formed 3D Nanoplasmonic Wells.

Surface-enhanced Raman scattering (SERS) has recently been considered as one of the most promising tools to directly analyze small molecules without labels, owing to advantages in sensitivity, specificity, and speed. However, collecting reproducible SERS signals from small molecules on substrates or in solutions is challenging because of random molecular adsorption on surfaces and laser-induced molecular convection in solutions. Herein, we report a novel and efficient way to collect SERS signals from solution samples using three-dimensional nanoplasmonic wells spontaneously formed by interfacial reactions between liquid polydimethylsiloxane (PDMS) and small droplets of metal ion solutions (e.g., HAuCl4 and AgNO3). A SERS signal is easily maximized at the center near the bottom of the well due to spherical feature of the fabricated wells and electromagnetic field enhancement by the metallic nanoparticles (e.g., Au and Ag) integrated on their surfaces. Through the systematic control over the volume, concentration, and composition of the metal ion solution, optical functions of the nanoplasmonic wells were optimized for SERS, which was further amplified by exploiting the plasmonic couplings with colloidal nanoparticles. By using the optimized nanoplasmonic wells and the detection protocol, we successfully obtained intrinsic spectra of biomolecules (e.g., adenine, glucose, amyloid ß) and toxic environmental molecules (e.g., 1,1'-diethyl-2,2'-cyanine iodide and chloromethyliothiazolinone/methylisothiazolinone) as well as Raman active molecules, such as rhodamine 6G and 1,2-bis(4-pyridyl)ethylene at a low concentrations down to the picomolar level. Our detection platform provides a powerful way to develop highly sensitive sensors and high-throughput analyzing protocols for fieldwork applications as well as diagnosing diseases.

Tunable Plasmonic Cavity for Label-free Detection of Small Molecules.

Owing to its high sensitivity and high selectivity along with rapid response time, plasmonic detection has gained considerable interest in a wide variety of sensing applications. To improve the fieldwork applicability and reliability of plasmonic detection, the integration of plasmonic nanoparticles into optical devices is desirable. Herein, we propose an integrated label-free detection platform comprising a plasmonic cavity that allows sensitive molecular detection via either surface-enhanced Raman scattering (SERS) or plasmon resonance energy transfer (PRET). A small droplet of metal ion solution spontaneously produces a plasmonic cavity on the surface of uncured poly(dimethylsiloxane) (PDMS), and as PDMS is cured, the metal ions are reduced to form a plasmonic antennae array on the cavity surface. Unique spherical feature and the integrated metallic nanoparticles of the cavity provide excellent optical functions to focus the incident light in the cavity and to rescatter the light absorbed by the nanoparticles. The optical properties of the plasmonic cavity for SERS or PRET are optimized by controlling the composition, size, and density of the metal nanoparticles. By using the cavity, we accomplish both 1000-fold sensitive detection and real-time monitoring of reactive oxygen species secreted by live cells via PRET. In addition, we achieve sensitive detection of trace amounts of toxic environmental molecules such as 5-chloro-2-methyl-4-isothiazolin-3-one/2-methyl-4-isothiazol-3-one (CMIT/MIT) and bisphenol A, as well as several small biomolecules such as glucose, adenine, and tryptophan, via SERS.