Simple and sensitive galactose monitoring based on capillary SERS sensor.

Galactosemia, a severe genetic metabolic disorder, results from the absence of galactose-degrading enzymes, leading to harmful galactose accumulation. In this study, we introduce a novel capillary-based surface-enhanced Raman spectroscopy (SERS) sensor for convenient and sensitive galactose detection. The developed sensor enhances SERS signals by introducing gold nanoparticles (Au NPs) onto the surface of silver nanoshells (Ag NSs) within a capillary, creating Ag NSs with Au NPs as satellites. Utilizing 4-mercaptophenylboronic acid (4-MPBA) as a Raman reporter molecule, the detection method relies on the conversion of 4-MPBA to 4-mercaptophenol (4-MPhOH) driven by hydrogen peroxide (H2O2) generated during galactose oxidation by galactose oxidase (GOx). A new SERS signal was observed, which was generated by H2O2 produced when galactose and GOx reacted. Our strategy yielded a quantitative change in the SERS signal, specifically in the band intensity ratio of 998 to 1076 cm-1 (I998/I1076) as the galactose concentration increased. Our capillary-based SERS biosensor provides a promising platform for early galactosemia diagnosis.

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.

Clinical relationship between blood concentration and clinical symptoms in aconitine intoxication.

BACKGROUND: Aconitine is well-known for its potential analgesic, anti-inflammatory, and circulation promoting effects and has been widely used as a folk medicine in South Korea. Owing to its extremely toxic nature and relatively low safety margin, intoxication is sometimes fatal. The toxic compound mainly affects the central nervous system, heart, and muscle, resulting in cardiovascular complications. PURPOSE: To determine the exact relationship between blood concentration of aconitine and clinical manifestation. BASIC PROCEDURES: The National Forensic Service (NFS) was commissioned to assist in a quantitative analysis of highly toxic aconitine and corresponding blood concentrations by analyzing the body fluids of three patients who were suspected of aconitine poisoning. MAIN FINDINGS: Aconitine blood values tested by the NFS showed that patients with a blood concentration below a certain level developed symptoms slowly and showed a high severity of clinical manifestation. There was no correlation between blood concentration and symptoms or ECG results. CONCLUSIONS: In case of suspected aconitine poisoning, an emergency care department should be visited, even with symptomatic improvement, and the patient should be monitored for at least 24 h, depending on the level of recovery and changes in ECG results.

General in Colloidal Nanoparticles.

It is almost impossible to fabricate size-controlled nanomaterials without full understanding about nanoscience, because nanomaterials sometimes suddenly grow up and precipitated, meanwhile other nanomaterials are disappeared during fabrication process. With this reason, it is necessary to understand the principle theories about nanoscience for fabrication of "well-defined" nanoparticles. This chapter explains basic theories about nanomaterials. And based on the theory, methods for controlling the size of nanoparticles and preventing the aggregation after fabrication are described.

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.

Optical and Electron Microscopy for Analysis of Nanomaterials.

Not only is fabrication important for research in materials science, but also materials characterization and analysis. Special microscopes capable of ultra-high magnification are more essential for observing and analyzing nanoparticles than for macro-size particles. Recently, electron microscopy (EM) and scanning probe microscopy (SPM) are commonly used for observing and analyzing nanoparticles. In this chapter, the basic principles of various techniques in optical and electron microscopy are described and classified. In particular, techniques such as transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are explained.

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.

Carbon Nanomaterials for Biomedical Application.

The use of carbon-based nanomaterials (CNs) with outstanding properties has been rising in many scientific and industrial application fields. These CNs represent a tunable alternative for applications with biomolecules, which allow interactions in either covalent or noncovalent way. Diverse carbon-derived nanomaterial family exhibits unique features and has been widely exploited in various biomedical applications, including biosensing, diagnosis, cancer therapy, drug delivery, and tissue engineering. In this chapter, we aim to present an overview of CNs with a particular interest in intrinsic structural, electronic, and chemical properties. In particular, the detailed properties and features of CNs and its derivatives, including carbon nanotube (CNT), graphene, graphene oxide (GO), and reduced GO (rGO) are summarized. The interesting biomedical applications are also reviewed in order to offer an overview of the possible fields for scientific and industrial applications of CNs.

Introduction of Nanobiotechnology.

Nano is a fine metric unit which means "one billionth." Nanotechnology is attracting attention as a technological basis to lead the fourth industry. By utilizing synergistic properties obtained from controlling the structure or arrangement of materials at the nanoscale, nanotechnology has evolved rapidly over the past half century and is active in a variety of fields such as materials, pharmaceuticals, and biology. This chapter briefly describes the concept and features of nanotechnology, as well as the preparation, analysis, characterization, and application of nanomaterials. Also, the prospects for nanotechnology along with the nanotoxicity are described.

Magnetic Nanoparticles.

Magnetic nanoparticles have been used in various fields such as data storage, biomedicine, or bioimaging with their unique magnetic property. With their low toxicity, the importance of magnetic nanoparticles keeps increasing especially in biological field. In this chapter, content suitable for scientific inquirers or undergraduates to acquire basic knowledge about nanotechnology is introduced and then recent research trends in nanotechnology are covered.

Bioapplications of Nanomaterials.

Nanobiotechnology is known as the application of nanoscaled techniques in biology which bridges natural science to living organism for improving the quality of life of humans. Nanotechnology was first issued in 1959 and has been rapidly developed, supplying numerous benefits to basic scientific academy and to clinical application including human healthcare, specifically in cancer therapy. This chapter discusses recent advances and potentials of nanotechnology in pharmaceutics, therapeutics, biosensing, bioimaging, and gene delivery that demonstrate the multifunctionality of nanotechnology.

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.

Ultra-Fine Control of Silica Shell Thickness on Silver Nanoparticle-Assembled Structures.

To study the distance-dependent electromagnetic field effects related to the enhancement and quenching mechanism of surface-enhanced Raman scattering (SERS) or fluorescence, it is essential to precisely control the distance from the surface of the metal nanoparticle (NP) to the target molecule by using a dielectric layer (e.g., SiO2, TiO2, and Al2O3). However, precisely controlling the thickness of this dielectric layer is challenging. Herein, we present a facile approach to control the thickness of the silica shell on silver nanoparticle-assembled silica nanocomposites, SiO2@Ag NPs, by controlling the number of reacting SiO2@Ag NPs and the silica precursor. Uniform silica shells with thicknesses in the range 5-40 nm were successfully fabricated. The proposed method for creating a homogeneous, precise, and fine silica coating on nanocomposites can potentially contribute to a comprehensive understanding of the distance-dependent electromagnetic field effects and optical properties of metal NPs.

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.

ZW800-PEG: A Renal Clearable Zwitterionic Near-Infrared Fluorophore for Potential Clinical Translation.

Near-infrared (NIR) fluorescence imaging has advanced medical imaging and image-guided interventions during the past three decades. Despite tremendous advances in imaging devices, surprisingly only a few dyes are currently available in the clinic. Previous fluorophores, ZW800-1A and ZW800-1C, significantly improved the poor performance of the FDA-approved indocyanine green. However, ZW800-1A is not stable in serum and ZW800-1C induces severe stacking in aqueous media. To solve such dilemmas, ZW800-PEG was designed by introducing a flexible yet stable thiol PEG linker. ZW800-PEG shows high solubility in both aqueous and organic solvents, thus improving renal clearance with minimal binding to serum proteins during systemic circulation. The sulfide group on the meso position of the heptamethine core improves serum stability and physicochemical properties including the maximum emission wavelength shift to 800 nm, enabling the use of ZW800-PEG for image-guided interventions and augmenting photothermal therapy.

Synthesis, Properties, and Biological Applications of Metallic Alloy Nanoparticles.

Metallic alloy nanoparticles are synthesized by combining two or more different metals. Bimetallic or trimetallic nanoparticles are considered more effective than monometallic nanoparticles because of their synergistic characteristics. In this review, we outline the structure, synthesis method, properties, and biological applications of metallic alloy nanoparticles based on their plasmonic, catalytic, and magnetic characteristics.

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.