Chiral-Induced Surface-Enhanced Raman Optical Activity on a Single-Particle Substrate.

Surface-enhanced Raman optical activity (SEROA) is a promising method for analyzing chiral molecules' molecular chirality and structural changes. However, conventional SEROA measurements face challenges related to substrate stability, signal uniformity, and interference from electronic circular dichroism (ECD). Therefore, in this study, we present a uniform and stable substrate for SEROA measurements by utilizing Au nanoparticles on the Au nanofilm structure to confine hotspots to the film-particle junctions and minimize ECD interference. This method also uses the induction of chirality from chiral molecules to achiral molecules to overcome the limitation of chiral molecules in SEROA measurements, specifically their lower signal efficiency. Successful chirality transfer is demonstrated through distinguishable SEROA signals when the l/d-alanine mixture is present. Enantiomeric discrimination of different l/d-alanine ratios was achieved with linear responses in the circular intensity difference (CID). Altogether, the proposed chiral-induced SEROA on the AuNP_on_AuNF substrate shows promising potential for detecting and characterizing structural changes in biomolecules, thus making it a valuable tool for various research applications.

Enhancement of the signal-to-noise ratio in fiber-optics based SERS detection by rough-cutting the end surface.

Fiber-optics based surface-enhanced Raman scattering (FO-SERS) has an unique advantage of being able to remotely detect analyte molecules because the fiber length can be adjusted as desired. However, the Raman signal of the fiber-optic material is so strong that it is an important challenge in utilization of optical fiber for remote SERS sensing. In this study, we found that the background noise signal was greatly reduced by ca. 32% compared to conventional fiber-optics with a flat surface cut. To confirm the feasibility of FO-SERS detection, silver nanoparticles labeled with 4-fluorobenzenethiol were attached onto the end surface of an optical fiber to form a SERS-signaling substrate. The SERS intensity from the fiber-optics with a roughened surface as SERS substrate was increased significantly with respect to signal-to-noise ratio (SNR) values compared to optical fibers with flat end surface. This result implies that the fiber-optics with roughened surface could be used as an efficient alternative for FO-SERS sensing platform.

Highly sensitive near-infrared SERS nanoprobes for in vivo imaging using gold-assembled silica nanoparticles with controllable nanogaps.

BACKGROUND: To take advantages, such as multiplex capacity, non-photobleaching property, and high sensitivity, of surface-enhanced Raman scattering (SERS)-based in vivo imaging, development of highly enhanced SERS nanoprobes in near-infrared (NIR) region is needed. A well-controlled morphology and biocompatibility are essential features of NIR SERS nanoprobes. Gold (Au)-assembled nanostructures with controllable nanogaps with highly enhanced SERS signals within multiple hotspots could be a breakthrough. RESULTS: Au-assembled silica (SiO2) nanoparticles (NPs) (SiO2@Au@Au NPs) as NIR SERS nanoprobes are synthesized using the seed-mediated growth method. SiO2@Au@Au NPs using six different sizes of Au NPs (SiO2@Au@Au50-SiO2@Au@Au500) were prepared by controlling the concentration of Au precursor in the growth step. The nanogaps between Au NPs on the SiO2 surface could be controlled from 4.16 to 0.98 nm by adjusting the concentration of Au precursor (hence increasing Au NP sizes), which resulted in the formation of effective SERS hotspots. SiO2@Au@Au500 NPs with a 0.98-nm gap showed a high SERS enhancement factor of approximately 3.8 × 106 under 785-nm photoexcitation. SiO2@Au@Au500 nanoprobes showed detectable in vivo SERS signals at a concentration of 16 µg/mL in animal tissue specimen at a depth of 7 mm. SiO2@Au@Au500 NPs with 14 different Raman label compounds exhibited distinct SERS signals upon subcutaneous injection into nude mice. CONCLUSIONS: SiO2@Au@Au NPs showed high potential for in vivo applications as multiplex nanoprobes with high SERS sensitivity in the NIR region.

Au-Ag assembled on silica nanoprobes for visual semiquantitative detection of prostate-specific antigen.

BACKGROUND: Blood prostate-specific antigen (PSA) levels are widely used as diagnostic biomarkers for prostate cancer. Lateral-flow immunoassay (LFIA)-based PSA detection can overcome the limitations associated with other methods. LFIAbased PSA detection in clinical samples enables prognosis and early diagnosis owing to the use of high-performance signal reporters. RESULTS: Here, a semiquantitative LFIA platform for PSA detection in blood was developed using Au-Ag nanoparticles (NPs) assembled on silica NPs (SiO2@Au-Ag NPs) that served as signal reporters. Synthesized SiO2@Au-Ag NPs exhibited a high absorbance at a wide wavelength range (400-800 nm), with a high scattering on nitrocellulose membrane test strips. In LFIA, the color intensity of the test line on the test strip differed depending on the PSA concentration (0.30-10.00 ng/mL), and bands for the test line on the test strip could be used as a standard. When clinical samples were assessed using this LFIA, a visual test line with particular color intensity observed on the test strip enabled the early diagnosis and prognosis of patients with prostate cancer based on PSA detection. In addition, the relative standard deviation of reproducibility was 1.41%, indicating high reproducibility, and the signal reporter showed good stability for 10 days. CONCLUSION: These characteristics of the signal reporter demonstrated the reliability of the LFIA platform for PSA detection, suggesting potential applications in clinical sample analysis.

Silica Nanoparticles.

Silica consists of one silicon atom and two oxygen atoms (SiO2) and is commonly used in various aspects of daily life. For example, it has been used as glass, insulator, and so on. Nowadays, silica is used as core reagents for fabricating and encapsulating nanoparticles (NPs). In this chapter, the usage of silica in nanotechnology is described. Synthesis and surface modification of silica nanoparticles (SiNPs), including via the Stöber method, reverse microemulsion method, and modified sol-gel method, are illustrated. Then, various NPs with silica encapsulation are explained. At last, the biological applications of those mentioned NPs are described.

Luminescent Nanomaterials (I).

From molecular probes, also known as fluorophores (typically emitting a longer wavelength than the absorbing wavelength), to inorganic nanoparticles, various light-emitting materials have been actively studied and developed for various applications in life science owing to their superior imaging and sensing ability. Especially after the breakthrough development of quantum dots (QDs), studies have pursued the development of the optical properties and biological applications of luminescent inorganic nanoparticles such as upconversion nanoparticles (UCNPs), metal nanoclusters, carbon dots, and so on. In this review, we first provide a brief explanation about the theoretical background and traditional concepts of molecular fluorophores. Then, currently developed luminescent nanoparticles are described as sensing and imaging platforms from general aspects to technical views.

Luminescent Nanomaterials (II).

In this review, we focus on sensing techniques and biological applications of various luminescent nanoparticles including quantum dot (QD), up-conversion nanoparticles (UCNPs) following the previous chapter. Fluorescent phenomena can be regulated or shifted by interaction between biological targets and luminescence probes depending on their distance, which is so-called FÓ§rster resonance energy transfer (FRET). QD-based FRET technique, which has been widely applied as a bioanalytical tool, is described. We discuss time-resolved fluorescence (TRF) imaging and flow cytometry technique, using photoluminescent nanoparticles with unique properties for effectively improving selectivity and sensitivity. Based on these techniques, bioanalytical and biomedical application, bioimaging with QD, UCNPs, and Euripium-activated luminescent nanoprobes are covered. Combination of optical property of these luminescent nanoparticles with special functions such as drug delivery, photothermal therapy (PTT), and photodynamic therapy (PDT) is also described.

Plasmonic Nanoparticles: Basics to Applications (I).

This review presents the main characteristics of metal nanoparticles (NPs), especially consisting of noble metal such as Au and Ag, and brief information on their synthesis methods. The physical and chemical properties of the metal NPs are described, with a particular focus on the optically variable properties (surface plasmon resonance based properties) and surface-enhanced Raman scattering of plasmonic materials. In addition, this chapter covers ways to achieve advances by utilizing their properties in the biological studies and medical fields (such as imaging, diagnostics, and therapeutics). These descriptions will help researchers new to nanomaterials for biomedical diagnosis to understand easily the related knowledge and also will help researchers involved in the biomedical field to learn about the latest research trends.

Plasmonic Nanoparticles: Advanced Researches (II).

Following the previous chapter, recent synthetic methods of metal-based nanoparticles and their applications based on plasmonic resonance properties are described in this chapter. This differs from the previous chapter, which described the general uses of metal-based nanoparticles, in that various recent advanced applications of metal-based nanoparticles are described in this chapter.

Conclusion and Perspective.

Nanotechnology is a rapidly growing area of development by numerous research groups across the world with its potential applications gaining recognition since the 1950s across various fields. During the last decade of the twentieth century, researchers have actively engaged in the synthesis of nanoparticles and investigation of their physicochemical properties. Advancing the research momentum forward at the beginning of the twenty-first century, rapid development of nanoscience allowed to demonstrate unprecedented advantages of the nanomaterials and its applications in a wide range of fields. The interdisciplinary nature of nanoscience and its expansion has led to establishment of new laboratories and research centers, with increasing needs on training and educating young scientists in advanced laboratory protocols. In addition, pedagogical demands in nanotechnology and nanomaterials have resulted an emergence of new dedicated curriculums at universities which has sped up the development of nanoscience and its contribution to the body of knowledge in natural science.

Silver-Assembled Silica Nanoparticles in Lateral Flow Immunoassay for Visual Inspection of Prostate-Specific Antigen.

Prostate-specific antigen (PSA) is the best-known biomarker for early diagnosis of prostate cancer. For prostate cancer in particular, the threshold level of PSA <4.0 ng/mL in clinical samples is an important indicator. Quick and easy visual detection of the PSA level greatly helps in early detection and treatment of prostate cancer and reducing mortality. In this study, we developed optimized silica-coated silver-assembled silica nanoparticles (SiO2@Ag@SiO2 NPs) that were applied to a visual lateral flow immunoassay (LFIA) platform for PSA detection. During synthesis, the ratio of silica NPs to silver nitrate changed, and as the synthesized NPs exhibited distinct UV spectra and colors, most optimized SiO2@Ag@SiO2 NPs showed the potential for early prostate cancer diagnosis. The PSA detection limit of our LFIA platform was 1.1 ng/mL. By applying each SiO2@Ag@SiO2 NP to the visual LFIA platform, optimized SiO2@Ag@SiO2 NPs were selected in the test strip, and clinical samples from prostate cancer patients were successfully detected as the boundaries of non-specific binding were clearly seen and the level of PSA was <4 ng/mL, thus providing an avenue for quick prostate cancer diagnosis and early treatment.

Template-Assisted Plasmonic Nanogap Shells for Highly Enhanced Detection of Cancer Biomarkers.

We present a template-assisted method for synthesizing nanogap shell structures for biomolecular detections based on surface-enhanced Raman scattering. The interior nanogap-containing a silver shell structure, referred to as a silver nanogap shell (Ag NGS), was fabricated on silver nanoparticles (Ag NPs)-coated silica, by adsorbing small aromatic thiol molecules on the Ag NPs. The Ag NGSs showed a high enhancement factor and good signal uniformity, using 785-nm excitation. We performed in vitro immunoassays using a prostate-specific antigen as a model cancer biomarker with a detection limit of 2 pg/mL. To demonstrate the versatility of Ag NGS nanoprobes, extracellular duplex surface-enhanced Raman scattering (SERS) imaging was also performed to evaluate the co-expression of cancer biomarkers, human epidermal growth factor-2 (HER2) and epidermal growth factor receptor (EGFR), in a non-small cell lung cancer cell line (H522). Developing highly sensitive Ag NGS nanoprobes that enable multiplex biomolecular detection and imaging can open up new possibilities for point-of-care diagnostics and provide appropriate treatment options and prognosis.

Reaction Kinetics-Mediated Control over Silver Nanogap Shells as Surface-Enhanced Raman Scattering Nanoprobes for Detection of Alzheimer's Disease Biomarkers.

It is very challenging to accurately quantify the amounts of amyloid peptides Aß40 and Aß42, which are Alzheimer's disease (AD) biomarkers, in blood owing to their low levels. This has driven the development of sensitive and noninvasive sensing methods for the early diagnosis of AD. Here, an approach for the synthesis of Ag nanogap shells (AgNGSs) is reported as surface-enhanced Raman scattering (SERS) colloidal nanoprobes for the sensitive, selective, and multiplexed detection of Aß40 and Aß42 in blood. Raman label chemicals used for SERS signal generation modulate the reaction rate for AgNGSs production through the formation of an Ag-thiolate lamella structure, enabling the control of nanogaps at one nanometer resolution. The AgNGSs embedded with the Raman label chemicals emit their unique SERS signals with a huge intensity enhancement of up to 107 and long-term stability. The AgNGS nanoprobes, conjugated with an antibody specific to Aß40 or Aß42, are able to detect these AD biomarkers in a multiplexed manner in human serum based on the AgNGS SERS signals. Detection is possible for amounts as low as 0.25 pg mL-1 . The AgNGS nanoprobe-based sandwich assay has a detection dynamic range two orders of magnitude wider than that of a conventional enzyme-linked immunosorbent assay.

Size-controllable and uniform gold bumpy nanocubes for single-particle-level surface-enhanced Raman scattering sensitivity.

Gold nanocubes modified to form roughened structures, namely, gold bumpy nanocubes (Au BNCs), with very strong and uniform single-particle surface-enhanced Raman scattering (SERS) intensity were developed. The Au BNCs were synthesized by controlled regrowth, competing with 4-aminothiophenol during gold nanocube growth. Under controlled conditions, Au BNCs of various sizes were successfully generated while maintaining a cubic outline. As the bumpy surfaces of the Au BNCs increased the number of hot spots on a single cubic nanoparticle, these nanoparticles exhibited 15-times stronger SERS than normal cubic nanoparticles. We expect that this unique nanostructure will be applicable in versatile fields as an ultrasensitive SERS nanoprobe or nanoantenna owing to its cubic outline and high uniformity, as well as the ease of particle size adjustment.

4-Mercaptobenzoic Acid Labeled Gold-Silver-Alloy-Embedded Silica Nanoparticles as an Internal Standard Containing Nanostructures for Sensitive Quantitative Thiram Detection.

In this study, SiO2@Au@4-MBA@Ag (4-mercaptobenzoic acid labeled gold-silver-alloy-embedded silica nanoparticles) nanomaterials were investigated for the detection of thiram, a pesticide. First, the presence of Au@4-MBA@Ag alloys on the surface of SiO2 was confirmed by the broad bands of ultraviolet-visible spectra in the range of 320-800 nm. The effect of the 4-MBA (4-mercaptobenzoic acid) concentration on the Ag shell deposition and its intrinsic SERS (surface-enhanced Raman scattering) signal was also studied. Ag shells were well coated on SiO2@Au@4-MBA in the range of 1-1000 µM. The SERS intensity of thiram-incubated SiO2@Au@4-MBA@Ag achieved the highest value by incubation with 500 µL thiram for 30 min, and SERS was measured at 200 µg/mL SiO2@Au@4-MBA@Ag. Finally, the SERS intensity of thiram at 560 cm-1 increased proportionally with the increase in thiram concentration in the range of 240-2400 ppb, with a limit of detection (LOD) of 72 ppb.

Control of Silver Coating on Raman Label Incorporated Gold Nanoparticles Assembled Silica Nanoparticles.

Signal reproducibility in surface-enhanced Raman scattering (SERS) remains a challenge, limiting the scope of the quantitative applications of SERS. This drawback in quantitative SERS sensing can be overcome by incorporating internal standard chemicals between the core and shell structures of metal nanoparticles (NPs). Herein, we prepared a SERS-active core Raman labeling compound (RLC) shell material, based on Au⁻Ag NPs and assembled silica NPs (SiO2@Au@RLC@Ag NPs). Three types of RLCs were used as candidates for internal standards, including 4-mercaptobenzoic acid (4-MBA), 4-aminothiophenol (4-ATP) and 4-methylbenzenethiol (4-MBT), and their effects on the deposition of a silver shell were investigated. The formation of the Ag shell was strongly dependent on the concentration of the silver ion. The negative charge of SiO2@Au@RLCs facilitated the formation of an Ag shell. In various pH solutions, the size of the Ag NPs was larger at a low pH and smaller at a higher pH, due to a decrease in the reduction rate. The results provide a deeper understanding of features in silver deposition, to guide further research and development of a strong and reliable SERS probe based on SiO2@Au@RLC@Ag NPs.

Fabrication of Localized Surface Plasmon Resonance Sensor Based on Optical Fiber and Micro Fluidic Channel.

This paper proposes Fiber-Optic Localized Surface Plasmon Resonance (FO LSPR) sensor combined with a micro fluidic channel, which enables continuous supply of fluid for bio-reaction. The proposed method prevents degradation of the sensing performance due to changes in measurement conditions. The feasibility of the FO LSPR sensor with a micro fluidic channel was demonstrated by computational fluid dynamics (CFD) simulation. Also, the proposed method was assessed by measuring the output intensity of the FO LSPR sensor at various refractive index solutions. Finally, a prostate-specific antigen (PSA) immunoassay was performed to evaluate the possibility of the fabricated sensor system as a biosensor.

Adenosine Triphosphate-Encapsulated Liposomes with Plasmonic Nanoparticles for Surface Enhanced Raman Scattering-Based Immunoassays.

In this study, we prepared adenosine triphosphate (ATP) encapsulated liposomes, and assessed their applicability for the surface enhanced Raman scattering (SERS)-based assays with gold-silver alloy (Au@Ag)-assembled silica nanoparticles (NPs; SiO2@Au@Ag). The liposomes were prepared by the thin film hydration method from a mixture of l-α-phosphatidylcholine, cholesterol, and PE-PEG2000 in chloroform; evaporating the solvent, followed by hydration of the resulting thin film with ATP in phosphate-buffered saline (PBS). Upon lysis of the liposome, the SERS intensity of the SiO2@Au@Ag NPs increased with the logarithm of number of ATP-encapsulated liposomes after lysis in the range of 8 × 106 to 8 × 1010. The detection limit of liposome was calculated to be 1.3 × 10-17 mol. The successful application of ATP-encapsulated liposomes to SiO2@Au@Ag NPs based SERS analysis has opened a new avenue for Raman label chemical (RCL)-encapsulated liposome-enhanced SERS-based immunoassays.

Virus templated gold nanocube chain for SERS nanoprobe.

A M13 virus based SERS nanoprobe is presented. Gold nanocubes closely aligned into chains along the length of the virus intensify Raman signals of various reporter molecules serving as specific labels. An antibody is expressed at one end to detect the analyte. This new SERS nanoprobe holds promise for infinitesimal and multiplexed detection of any antigen.

Physicochemical determinants of multiwalled carbon nanotubes on cellular toxicity: influence of a synthetic method and post-treatment.

Since the discovery of carbon nanotubes (CNTs), scientists have performed extensive studies on nanotubes in the fields of materials science, physics, and electronic engineering. Because multiwalled CNTs (MWCNTs) are not homogeneous materials, and because it is not feasible to test every newly synthesized MWCNT, this study was aimed at investigating the physicochemical properties that primarily determine the cellular toxicity of MWCNTs. This study analyzed the relationship between cell viability and physicochemical characteristics following exposure to eight different MWCNTs. We generated eight different MWCNTs using various synthetic methods and post-treatments. From this analysis, we sought to identify the major physicochemical determinants that could predict the cellular toxicity of MWCNTs, regardless of the synthetic method and post-treatment conditions. Creation of binding sites on the tube walls by breaking C-C bonds played a pivotal role in increasing toxicity and was most clearly demonstrated by a Raman G peak shift and the ID/IG ratio. In addition, several factors were found to be strongly related to cellular toxicity: surface charge in the case of MWCNTs created by the chemical vapor deposition method and surface area and EPR intensity in the case of MWCNTs created by the arc discharge based method. The methods developed in this study could be applied to the prediction of the toxicity of newly synthesized MWCNTs.