Nanostructured Substrate-Mediated Bubble Degassing in Microfluidic Systems.

Microfluidic platforms have been widely used in a variety of fields owing to their numerous advantages. The prevention and prompt removal of air bubbles from microchannels are important to ensuring the optimal functioning of microfluidic devices. The entrapment of bubbles in the microchannels can result in flow instability and device performance disruption. Active and passive methods are the primary categories of degassing technologies. Active methods rely on external equipment, and passive methods operate autonomously without any external sources. This study proposed a passive degassing method that employs a nanoscale surface morphology integrated into the substrate of a microfluidic device. Nanostructures exhibit a microchannel geometry and are fabricated based on surface micromachining technology using silver ink and chemical etching. Consequently, the gas permeability is enhanced, resulting in effective degassing through the nanostructure. The performance of this degassing method was characterized under varying substrate permeabilities and input pressure conditions, and it was found that increased permeability facilitates the degassing performance. Furthermore, the applicability of our method was demonstrated by using a serpentine channel design prone to gas entrapment, particularly in the corner regions. The nanostructured substrate exhibited significantly improved degassing performance under the given pressure conditions in comparison to the glass substrate.

Recent Trends in Lateral Flow Immunoassays with Optical Nanoparticles.

Rapid, accurate, and convenient diagnosis is essential for effective disease management. Various detection methods, such as enzyme-linked immunosorbent assay, have been extensively used, with lateral flow immunoassay (LFIA) recently emerging as a major diagnostic tool. Nanoparticles (NPs) with characteristic optical properties are used as probes for LFIA, and researchers have presented various types of optical NPs with modified optical properties. Herein, we review the literature on LFIA with optical NPs for the detection of specific targets in the context of diagnostics.

In Vitro Tracking of Human Umbilical Vein Endothelial Cells Using Ultra-Sensitive Quantum Dot-Embedded Silica Nanoparticles.

The nanoscale spatiotemporal resolution of single-particle tracking (SPT) renders it a powerful method for exploring single-molecule dynamics in living cells or tissues, despite the disadvantages of using traditional organic fluorescence probes, such as the weak fluorescent signal against the strong cellular autofluorescence background coupled with a fast-photobleaching rate. Quantum dots (QDs), which enable tracking targets in multiple colors, have been proposed as an alternative to traditional organic fluorescence dyes; however, they are not ideally suitable for applying SPT due to their hydrophobicity, cytotoxicity, and blinking problems. This study reports an improved SPT method using silica-coated QD-embedded silica nanoparticles (QD2), which represent brighter fluorescence and are less toxic than single QDs. After treatment of QD2 in 10 µg/mL, the label was retained for 96 h with 83.76% of labeling efficiency, without impaired cell function such as angiogenesis. The improved stability of QD2 facilitates the visualization of in situ endothelial vessel formation without real-time staining. Cells retain QD2 fluorescence signal for 15 days at 4 °C without significant photobleaching, indicating that QD2 has overcome the limitations of SPT enabling long-term intracellular tracking. These results proved that QD2 could be used for SPT as a substitute for traditional organic fluorophores or single quantum dots, with its photostability, biocompatibility, and superior brightness.

High-quantum yield alloy-typed core/shell CdSeZnS/ZnS quantum dots for bio-applications.

BACKGROUND: Quantum dots (QDs) have been used as fluorophores in various imaging fields owing to their strong fluorescent intensity, high quantum yield (QY), and narrow emission bandwidth. However, the application of QDs to bio-imaging is limited because the QY of QDs decreases substantially during the surface modification step for bio-application. RESULTS: In this study, we fabricated alloy-typed core/shell CdSeZnS/ZnS quantum dots (alloy QDs) that showed higher quantum yield and stability during the surface modification for hydrophilization compared with conventional CdSe/CdS/ZnS multilayer quantum dots (MQDs). The structure of the alloy QDs was confirmed using time-of-flight medium-energy ion scattering spectroscopy. The alloy QDs exhibited strong fluorescence and a high QY of 98.0%. After hydrophilic surface modification, the alloy QDs exhibited a QY of 84.7%, which is 1.5 times higher than that of MQDs. The QY was 77.8% after the alloy QDs were conjugated with folic acid (FA). Alloy QDs and MQDs, after conjugation with FA, were successfully used for targeting human KB cells. The alloy QDs exhibited a stronger fluorescence signal than MQD; these signals were retained in the popliteal lymph node area for 24 h. CONCLUSION: The alloy QDs maintained a higher QY in hydrophilization for biological applications than MQDs. And also, alloy QDs showed the potential as nanoprobes for highly sensitive bioimaging analysis.

Highly Bright Silica-Coated InP/ZnS Quantum Dot-Embedded Silica Nanoparticles as Biocompatible Nanoprobes.

Quantum dots (QDs) have outstanding optical properties such as strong fluorescence, excellent photostability, broad absorption spectra, and narrow emission bands, which make them useful for bioimaging. However, cadmium (Cd)-based QDs, which have been widely studied, have potential toxicity problems. Cd-free QDs have also been studied, but their weak photoluminescence (PL) intensity makes their practical use in bioimaging challenging. In this study, Cd-free QD nanoprobes for bioimaging were fabricated by densely embedding multiple indium phosphide/zinc sulfide (InP/ZnS) QDs onto silica templates and coating them with a silica shell. The fabricated silica-coated InP/ZnS QD-embedded silica nanoparticles (SiO2@InP QDs@SiO2 NPs) exhibited hydrophilic properties because of the surface silica shell. The quantum yield (QY), maximum emission peak wavelength, and full-width half-maximum (FWHM) of the final fabricated SiO2@InP QDs@SiO2 NPs were 6.61%, 527.01 nm, and 44.62 nm, respectively. Moreover, the brightness of the particles could be easily controlled by adjusting the amount of InP/ZnS QDs in the SiO2@InP QDs@SiO2 NPs. When SiO2@InP QDs@SiO2 NPs were administered to tumor syngeneic mice, the fluorescence signal was prominently detected in the tumor because of the preferential distribution of the SiO2@InP QDs@SiO2 NPs, demonstrating their applicability in bioimaging with NPs. Thus, SiO2@InP QDs@SiO2 NPs have the potential to successfully replace Cd-based QDs as highly bright and biocompatible fluorescent nanoprobes.

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.

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.

Optimizing the Aspect Ratio of Nanopatterned Mesoporous TiO2 Thin-Film Layer to Improve Energy Conversion Efficiency of Perovskite Solar Cells.

The energy conversion efficiency (ECE) (η), current density (Jsc), open-circuit voltage (Voc), and fill factor (ff) of perovskite solar cells were studied by using the transmittance of a nanopatterned mesoporous TiO2 (mp-TiO2) thin-film layer. To improve the ECE of perovskite solar cells, a mp-TiO2 thin-film layer was prepared to be used as an electron transport layer (ETL) via the nanoimprinting method for nanopatterning, which was controlled by the aspect ratio. The nanopatterned mp-TiO2 thin-film layer had a uniform and well-designed structure, and the diameter of nanopatterning was 280 nm. The aspect ratio was controlled at the depths of 75, 97, 127, and 167 nm, and the perovskite solar cell was fabricated with different depths. The ECE of the perovskite solar cells with the nanopatterned mp-TiO2 thin-film layer was 14.50%, 15.30%, 15.83%, or 14.24%, which is higher than that of a non-nanopatterned mp-TiO2 thin-film layer (14.07%). The enhancement of ECE was attributed to the transmittance of the nanopatterned mp-TiO2 thin-film layer that is due to the improvement of the electron generation. As a result, better electron generation affected the electron density, and Jsc increased the Voc, and ff of perovskite solar cells.

Facile Histamine Detection by Surface-Enhanced Raman Scattering using SiO2@Au@Ag Alloy Nanoparticles.

Histamine intoxication associated with seafood consumption represents a global health problem. The consumption of high concentrations of histamine can cause illnesses ranging from light symptoms, such as a prickling sensation, to death. In this study, gold-silver alloy-embedded silica (SiO2@Au@Ag) nanoparticles were created to detect histamine using surface-enhanced Raman scattering (SERS). The optimal histamine SERS signal was measured following incubation with 125 µg/mL of SiO2@Au@Ag for 2 h, with a material-to-histamine solution volume ratio of 1:5 and a phosphate-buffered saline-Tween 20 (PBS-T) solvent at pH 7. The SERS intensity of the histamine increased proportionally with the increase in histamine concentration in the range 0.1-0.8 mM, with a limit of detection of 3.698 ppm. Our findings demonstrate the applicability of SERS using nanomaterials for histamine detection. In addition, this study demonstrates that nanoalloys could have a broad application in the future.

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.

Polyethylene Glycol-Engrafted Graphene Oxide as Biocompatible Materials for Peptide Nucleic Acid Delivery into Cells.

Graphene oxide (GO) is known to strongly bind single-stranded nucleic acids with fluorescence quenching near the GO surface. However, GO exhibits weak biocompatibility characteristics, such as low dispersibility in cell culture media and significant cytotoxicity. To improve dispersibility in cell culture media and cell viability of GO, we prepared nanosized GO (nGO) constructs and modified the nGO surface using polyethylene glycol (PEG-nGO). Single-stranded peptide nucleic acid (PNA) was adsorbed onto the PEG-nGO and was readily desorbed by adding complementary RNA or under low pH conditions. PNA adsorbed on the PEG-nGO was efficiently delivered into lung cancer cells via endocytosis without affecting cell viability. Furthermore, antisense PNA delivered using PEG-nGO effectively downregulated the expression of the target gene in cancer cells. Our results suggest that PEG-nGO is a biocompatible carrier useful for PNA delivery into cells and serves as a promising gene delivery tool.

Nonwettable Hierarchical Structure Effect on Droplet Impact and Spreading Dynamics.

In this study, the nano/micro hierarchical structure effect of a nonwettable surface on droplet impact was investigated by high-speed visualization. A dual-scale structure of a superhydrophobic surface was designed for manipulating a wide range of capillary pressures (103-106 Pa), and it was supposed to trigger a hierarchical effect on the droplet dynamics. Distilled water droplets of various sizes and initial velocity were subjected to the prepared samples, and the impact behavior, the spreading diameter, and contacted time, were quantitatively measured. The apparent maximum spreading and contact time of the low Weber number ( We#) condition was less dependent on the microscaled design factor of the multiscale-fabricated surface. However, in the high We# condition, the wavy formation shape and the fragmented criteria of the droplet impact were affected by the configuration of the surface morphology. The hierarchical effect from the dual-scale structure on droplet spreading dynamics has been discussed through a balance between capillary pressure induced by the structure and the dynamic pressure of droplet impact.

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.

Evaluation of three-dimensional position change of the condylar head after orthognathic surgery using computer-aided design/computer-aided manufacturing-made condyle positioning jig.

This study was performed to evaluate the efficacy of computer-aided design/computer-aided manufacturing (CAM/CAD)-made condyle positioning jig in orthognathic surgery. The sample consisted of 40 mandibular condyles of 20 patients with class III malocclusion who underwent bilateral sagittal split ramus osteotomy with semirigid fixation (6 men and 14 women; mean age, 25 y; mean amount of mandibular setback, 5.8 mm). Exclusion criteria were patients who needed surgical correction of the frontal ramal inclination and had signs and symptoms of the temporomandibular disorder before surgery. Three-dimensional computed tomograms were taken 1 month before the surgery (T1) and 1 day after the surgery (T2). The condylar position was evaluated at the T1 and T2 stages on the axial, frontal, and sagittal aspects in the three-dimensional coordinates. The linear change of the posterior border of the proximal segment of the ramus between T1 and T2 was also evaluated in 30 condyles (15 patients), with the exception of 10 condyles of 5 patients who received mandibular angle reduction surgery. There was no significant difference in the condylar position in the frontal and sagittal aspects (P > 0.05). Although there was a significant difference in the condylar position in the axial aspect (P < 0.01), the amount of difference was less than 1 mm and 1 degree; it can be considered clinically nonsignificant. In the linear change of the posterior border of the proximal segment of the ramus, the mean change was 1.4 mm and 60% of the samples showed a minimal change of less than 1 mm. The results of this study suggest that CAD/CAM-made condyle positioning jig is easy to install and reliable to use in orthognathic surgery.

Performance Improvement of an STS304-Based Dispensing Needle via Electrochemical Etching.

In this study, we explored the formation of micro-/nanosized porous structures on the surface of a needle composed of STS304 and examined the effect of conventional needles and needles capable of liquid ejection. Aqua regia, composed of HCl and HNO3, was electrochemically etched to form appropriately sized micro-/nanoporous structures. We observed that when dispensing liquids with low surface tension, they do not immediately fall downward but instead spread over the exterior surface of the needle before falling. We found that the extent of spreading on the surface is influenced by an etched porous structure. Furthermore, to analyze the effect of surface tension differences, we dispensed liquids with varying surface tensions using etched needles. Through the analysis, it was confirmed that, despite the low surface tension, the ejected droplet volume and speed could be stably maintained on the etched needle. This indicates that the spreading phenomenon of the liquid on the needle surface just before ejection can be controlled by the micro/nanoporous structure. We anticipate that these characteristics of etched needles could be utilized in industries where precision dispensing of low-surface-tension liquids is essential.

Silica Encapsulation of Hydrophobic Optical NP-Embedded Silica Particles with Trimethoxy(2-Phenylethyl)silane.

Nanoparticles (NP) with optical properties embedded silica particles have been widely used in various fields because of their unique properties. The surfaces of optical NPs have been modified with various organic ligands to maintain their unique optical properties and colloidal stability. Among the surface modification methods, silica encapsulation of optical NPs is widely used to enhance their biocompatibility and stability. However, in the case of NPs with hydrophobic ligands on the surface, the ligands that determine the optical properties of the NPs may detach from the NPs, thereby changing the optical properties during silica encapsulation. Herein, we report a generally applicable silica encapsulation method using trimethoxy(2-phenylethyl)silane (TMPS) for non-hydrophilic optical NPs, such as quantum dots (QDs) and gold NPs. This silica encapsulation method was applied to fabricate multiple silica-encapsulated QD-embedded silica NPs (SiO2@QD@SiO2 NPs; QD2) and multiple silica-encapsulated gold NP-embedded silica NPs labeled with 2-naphthalene thiol (SiO2@Au2-NT@SiO2). The fabricated silica-encapsulated NPs exhibited optical properties without significant changes in the quantum yield or Raman signal intensity.

Drop impact characteristics and structure effects of hydrophobic surfaces with micro- and/or nanoscaled structures.

We report the drop impact characteristics on four hydrophobic surfaces with different well-scale structures (smooth, nano, micro, and hierarchical micro/nano) and the effects of those structures on the behavior of water drops during impact. The specimens were fabricated using silicon wet etching, black silicon formation, or the combination of these methods. On the surfaces, the microstructures form obstacles to drop spreading and retracting, the nanostructures give extreme water-repellency, and the hierarchical micro/nanostructures facilitate drop fragmentation. The maximum spreading factor (D*(max)) differed among the structures. On the basis of published models of D*(max), we interpret the results of our experiment and suggest reasonable explanations for these differences. Especially, the micro/nanostructures caused instability of the interface between liquid and air at Weber number We > ~80 and impacting drops fragmented at We > ~150.

Hyaluronic Acid Nanoparticles as a Topical Agent for Treating Psoriasis.

Although conventional topical approaches for treating psoriasis have been offered as an alternative, there are still unmet medical needs such as low skin-penetrating efficacy and off-target adverse effects. A hyaluronic acid nanoparticle (HA-NP) formed by self-assembly of HA-hydrophobic moiety conjugates has been broadly studied as a nanocarrier for long-term and target-specific delivery of drugs, owing to their excellent physicochemical and biological characteristics. Here, we identify HA-NPs as topical therapeutics for treating psoriasis using in vivo skin penetration studies and psoriasis animal models. Transcutaneously administered HA-NPs were found to be accumulated and associated with pro-inflammatory macrophages in the inflamed dermis of a psoriasis mouse model. Importantly, HA-NP exerted potent therapeutic efficacy against psoriasis-like skin dermatitis in a size-dependent manner by suppressing innate immune responses and restoring skin barrier function without overt toxicity signs. The therapeutic efficacy of HA-NPs on psoriasis-like skin dermatitis was due to the outermost hydrophilic HA shell layer of HA-NPs, independent of the molecular weight of HA and hydrophobic moiety, and comparable with that of other conventional psoriasis therapeutics widely used in the clinical settings. Overall, HA-NPs have the potential as a topical nanomedicine for treating psoriasis effectively and safely.

Multi-Quantum Dots-Embedded Silica-Encapsulated Nanoparticle-Based Lateral Flow Assay for Highly Sensitive Exosome Detection.

Exosomes are attracting attention as new biomarkers for monitoring the diagnosis and prognosis of certain diseases. Colorimetric-based lateral-flow assays have been previously used to detect exosomes, but these have the disadvantage of a high limit of detection. Here, we introduce a new technique to improve exosome detection. In our approach, highly bright multi-quantum dots embedded in silica-encapsulated nanoparticles (M-QD-SNs), which have uniform size and are brighter than single quantum dots, were applied to the lateral flow immunoassay method to sensitively detect exosomes. Anti-CD63 antibodies were introduced on the surface of the M-QD-SNs, and a lateral flow immunoassay with the M-QD-SNs was conducted to detect human foreskin fibroblast (HFF) exosomes. Exosome samples included a wide range of concentrations from 100 to 1000 exosomes/µL, and the detection limit of our newly designed system was 117.94 exosome/µL, which was 11 times lower than the previously reported limits. Additionally, exosomes were selectively detected relative to the negative controls, liposomes, and newborn calf serum, confirming that this method prevented non-specific binding. Thus, our study demonstrates that highly sensitive and quantitative exosome detection can be conducted quickly and accurately by using lateral immunochromatographic analysis with M-QD-SNs.