Single-Step LRET Aptasensor for Rapid Mycotoxin Detection.

Contamination of foods by mycotoxins is a common yet serious problem. Owing to the increase in consumption of fresh produce, consumers have become aware of food safety issues caused by mycotoxins. Therefore, rapid and sensitive mycotoxin detection is in great demand in fields such as food safety and public health. Here we report a single-step luminescence resonance energy transfer (LRET) aptasensor for mycotoxin detection. To accomplish the single-step sensor, our sensor was constructed by linking a quencher-labeled aptamer through a linker to the surface of upconversion nanoparticles (UCNPs). Our LRET aptasensor is composed of Mn2+-doped NaYF4:Yb3+,Er3+ UCNPs as the LRET donor, and black hole quencher 3 (BHQ3) as the acceptor. The maximum quenching efficiency is obtained by modulating the linker length, which controls the distance between the quencher and the UCNPs. Our distinctive design of LRET aptasensor allows detection of mycotoxins selectively in colored food samples within 10 min without multiple bioassay steps. We believe our single-step aptasensor has a significant potential for on-site detection of food contaminants, environmental pollutants, and biological metabolites.

Asymmetric Nanocrescent Antenna on Upconversion Nanocrystal.

Frequency upconversion activated with lanthanide has attracted attention in various real-world applications, because it is far simpler and more efficient than traditional nonlinear susceptibility-based frequency upconversion, such as second harmonic generation. However, the quantum yield of frequency upconversion of lanthanide-based upconversion nanocrystals remains inefficient for practical applications, and spatial control of upconverted emission is not yet developed. Here, we developed an asymmetric nanocrescent antenna on upconversion nanocrystal (ANAU) to deliver excitation light effectively to the core of upconversion nanocrystal by nanofocusing light and generating asymmetric frequency upconverted emission concentrated toward the tip region. ANAUs were fabricated by high-angle deposition (60°) of gold (Au) on the isolated upconversion nanoparticles supported by nanopillars then moved to refractive-index matched substrate for orientation-dependent upconversion luminescence analysis in the single-nanoparticle scale. We studied shape-dependent nanofocusing efficiency of nanocrescent antennae as a function of the tip-to-tip distance by modulating the deposition angle. The generation of asymmetric frequency upconverted emission toward the tip region was simulated by the asymmetric far-field radiation pattern of dipoles in the nanocrescent antenna and experimentally demonstrated by the orientation-dependent photon intensity of frequency upconverted emission of an ANAU. This finding provides a new way to improve frequency upconversion using an antenna, which locally increases the excitation light and generates the radiation power to certain directions for various applications.

Wearable Localized Surface Plasmon Resonance-Based Biosensor with Highly Sensitive and Direct Detection of Cortisol in Human Sweat.

Wearable biosensors have the potential for developing individualized health evaluation and detection systems owing to their ability to provide continuous real-time physiological data. Among various wearable biosensors, localized surface plasmon resonance (LSPR)-based wearable sensors can be versatile in various practical applications owing to their sensitive interactions with specific analytes. Understanding and analyzing endocrine responses to stress is particularly crucial for evaluating human performance, diagnosing stress-related diseases, and monitoring mental health, as stress takes a serious toll on physiological health and psychological well-being. Cortisol is an essential biomarker of stress because of the close relationship between cortisol concentration in the human body and stress level. In this study, a flexible LSPR biosensor was manufactured to detect cortisol levels in the human body by depositing gold nanoparticle (AuNP) layers on a 3-aminopropyltriethoxysilane (APTES)-functionalized poly (dimethylsiloxane) (PDMS) substrate. Subsequently, an aptamer was immobilized on the surface of the LSPR substrate, enabling highly sensitive and selective cortisol capture owing to its specific cortisol recognition. The biosensor exhibited excellent detection ability in cortisol solutions of various concentrations ranging from 0.1 to 1000 nM with a detection limit of 0.1 nM. The flexible LSPR biosensor also demonstrated good stability under various mechanical deformations. Furthermore, the cortisol levels of the flexible LSPR biosensor were also measured in the human epidermis before and after exercise as well as in the morning and afternoon. Our biosensors, which combine easily manufactured flexible sensors with sensitive cortisol-detecting molecules to measure human stress levels, could be versatile candidates for human-friendly products.

Plasmonic Approach to Fluorescence Enhancement of Mesoporous Silica-Coated Gold Nanorods for Highly Sensitive Influenza A Virus Detection Using Lateral Flow Immunosensor.

Rapid diagnostic tests based on the lateral flow immunoassay (LFI) enable early identification of viral infection, owing to simple interpretation, short turnaround time, and timely isolation of patients to minimize viral transmission among communities. However, the LFI system requires improvement in the detection sensitivity to match the accuracy of nucleic acid amplification tests. Fluorescence-based LFIs are more sensitive and specific than absorption-based LFIs, but their performance is significantly affected by fundamental issues related to the quantum yield and photobleaching of fluorophores. Metal-enhanced fluorescence (MEF), which is a plasmonic effect in the vicinity of metallic nanoparticles, can be an effective strategy to improve the detection sensitivity of fluorescence-based LFIs. The key factors for obtaining a strong plasmonic effect include the distance and spectral overlap of the metal and fluorophore in the MEF system. In this study, MEF probes were designed based on core-shell nanostructures employing a gold nanorod core, mesoporous silica shell, and cyanine 5 fluorophore. To optimize the efficiency of MEF probes incorporated on the LFI platform (MEF-LFI), we experimentally and theoretically investigated the distance dependence of plasmonic coupling between cyanine 5 and gold nanorods by adjusting the shell thickness, resulting in significant fluorescence enhancement. The proposed MEF-LFI enabled highly sensitive detection of influenza A virus (IAV) nucleocapsid protein with a detection limit of 0.52 pg mL-1 within 20 min and showed high specificity and accuracy for determining IAV clinical samples. Overall, our findings demonstrate the potential of this method as an effective tool for molecular diagnosis under emergency conditions.

Targetable gold nanorods for epithelial cancer therapy guided by near-IR absorption imaging.

Well-designed nanoparticle-mediated, image-guided cancer therapy has attracted interest for increasing the efficacy of cancer treatment. A new class of smart theragnostic nanoprobes employing cetuximab (CET)-conjugated polyethylene glycol (PEG)ylated gold nanorods (CET-PGNRs) is presented; these nanoprobes target epithelial cancer cells using near-infrared light. The cetyltrimethylammonium bromide bilayer on GNRs is replaced with heterobifunctional PEG (COOH-PEG-SH) to serve as a biocompatible stabilizer and to increase specificity. The carboxylated GNRs are further functionalized with CET using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC-NHS) chemistry. To assess the potential of such GNRs, their optical properties, biocompatibility, colloidal stability, in vitro/in vivo binding affinities for cancer cells, absorption imaging, and photothermal therapy effects are investigated. CET-PGNRs exhibit excellent tumor targeting ability and strong potential for simultaneous absorption imaging and photothermal ablation of epithelial cancer cells.

The work function of doped polyaniline nanoparticles observed by Kelvin probe force microscopy.

The work function of polyaniline nanoparticles in the emeraldine base state was determined by Kelvin probe force microscopy to be ~270 meV higher than that of similar nanoparticles in the emeraldine salt state. Normal tapping mode atomic force microscopy could not be used to distinguish between the particles due to their similar morphologies and sizes. Moreover, other potential measurement systems, such as using zeta potentials, were not suitable for the measurement of surface charges of doped nanoparticles due to their encapsulation by interfering chemical groups. Kelvin probe force microscopy can be used to overcome these limitations and unambiguously distinguish between the bare and doped polyaniline nanoparticles.

Programmed Shape-Morphing Material Using Single-Layer 4D Printing System.

The single-layer 4D printing technology that can be controllable in response to external stimuli is a tremendous challenge in many areas, including smart materials, robotics, and drug delivery systems. The single-layer 4D printing technique was enabled by light-focusing, which results in the difference of mechanical properties such as the coefficient of thermal expansion or Young's modulus between focused and unfocused regions. However, 4D printing to the desired shape using single-layered material is challenging. In this paper, we demonstrate the programmed shape morphing by patterning both the static and shape-morphing layers using a single-layer 4D printing system. A shape-morphing layer is formulated by short-time (<3 s) illumination in UV light. Then a static layer is formulated by longer-time (>3 s) illumination in UV light. We expect this technique to lead to the development of micro-scale soft robots.

Magnetically controlled reversible shape-morphing microrobots with real-time X-ray imaging for stomach cancer applications.

Stomach cancer is a global health concern as millions of cases are reported each year. In the present study, we developed a pH-responsive microrobot with good biocompatibility, magnetic-field controlled movements, and the ability to be visualized via X-ray imaging. The microrobot consisted of composite resin and a pH-responsive layer. This microrobot was found to fold itself in high pH environments and unfold itself in low pH environments. In addition, the neodymium (NdFeB) magnetic nanoparticles present inside the composite resin provided the microrobot with an ability to be controlled by a magnetic field through an electromagnetic actuation system, and the monomeric triiodobenzoate-based particles were found to act as contrast agents for real-time X-ray imaging. The doxorubicin coating on the microrobot's surface resulted in a high cancer-cell killing effect. Finally, we demonstrated the proposed microrobot under an ex vivo environment using a pig's stomach. Thus, this approach can be a potential alternative to targeted drug carriers, especially for stomach cancer applications.

Microrobot with Gyroid Surface and Gold Nanostar for High Drug Loading and Near-Infrared-Triggered Chemo-Photothermal Therapy.

The use of untethered microrobots for precise synergistic anticancer drug delivery and controlled release has attracted attention over the past decade. A high surface area of the microrobot is desirable to achieve greater therapeutic effect by increasing the drug load. Therefore, various nano- or microporous microrobot structures have been developed to load more drugs. However, as most porous structures are not interconnected deep inside, the drug-loading efficiency may be reduced. Here, we propose a magnetically guided helical microrobot with a Gyroid surface for high drug-loading efficiency and precise drug delivery. All spaces inside the proposed microrobot are interconnected, thereby enabling drug loading deep inside the structure. Moreover, we introduce gold nanostars on the microrobot structure for near-infrared-induced photothermal therapy and triggering drug release. The results of this study encourage further exploration of a high loading efficiency in cell-based therapeutics, such as stem cells or immune cells, for microrobot-based drug-delivery systems.

Multifunctional microrobot with real-time visualization and magnetic resonance imaging for chemoembolization therapy of liver cancer.

Microrobots that can be precisely guided to target lesions have been studied for in vivo medical applications. However, existing microrobots have challenges in vivo such as biocompatibility, biodegradability, actuation module, and intra- and postoperative imaging. This study reports microrobots visualized with real-time x-ray and magnetic resonance imaging (MRI) that can be magnetically guided to tumor feeding vessels for transcatheter liver chemoembolization in vivo. The microrobots, composed of a hydrogel-enveloped porous structure and magnetic nanoparticles, enable targeted delivery of therapeutic and imaging agents via magnetic guidance from the actuation module under real-time x-ray imaging. In addition, the microrobots can be tracked using MRI as postoperative imaging and then slowly degrade over time. The in vivo validation of microrobot system-mediated chemoembolization was demonstrated in a rat liver with a tumor model. The proposed microrobot provides an advanced medical robotic platform that can overcome the limitations of existing microrobots and current liver chemoembolization.

Optimization of Field-Free Point Position, Gradient Field and Ferromagnetic Polymer Ratio for Enhanced Navigation of Magnetically Controlled Polymer-Based Microrobots in Blood Vessel.

Microscale and nanoscale robots, frequently referred to as future cargo systems for targeted drug delivery, can effectively convert magnetic energy into locomotion. However, navigating and imaging them within a complex colloidal vascular system at a clinical scale is exigent. Hence, a more precise and enhanced hybrid control navigation and imaging system is necessary. Magnetic particle imaging (MPI) has been successfully applied to visualize the ensemble of superparamagnetic nanoparticles (MNPs) with high temporal sensitivity. MPI uses the concept of field-free point (FFP) mechanism in the principal magnetic field. The gradient magnetic field (|∇B|) of MPI scanners can generate sufficient magnetic force in MNPs; hence, it has been recently used to navigate nanosized particles and micron-sized swimmers. In this article, we present a simulation analysis of the optimized navigation of an ensemble of microsized polymer MNP-based drug carriers in blood vessels. Initially, an ideal two-dimensional FFP case is employed for the basic optimization of the FFP position to achieve efficient navigation. Thereafter, a nine-coil electromagnetic actuation simulation system is developed to generate and manipulate the FFP position and |∇B|. Under certain vessel and fluid conditions, the particle trajectories of different ferromagnetic polymer ratios and |∇B| were compared to optimize the FFP position.

Bio-inspired Ag nanovilli-based sandwich-type SERS aptasensor for ultrasensitive and selective detection of 25-hydroxy vitamin D3.

Vitamin D has been identified as an essential biomarker for various diseases such as rheumatoid arthritis, cancer, and cardiovascular diseases. Recently, many reports have demonstrated a potential link between vitamin D and systemic infections, including coronavirus disease 2019. The villi of the small intestine increase the surface area of the intestinal walls, demonstrating exceptionally efficient absorption of nutrients in the lumen and adding digestive secretions. In this study, based on the villi structure, we developed a bio-inspired silver nanovilli-based sandwich-type surface enhanced Raman scattering aptasensor for the ultrasensitive and selective detection of 25-hydroxy vitamin D3. The densely packed nanovilli structure enhanced the Raman signal, forming hotspots owing to its large surface area. Using experiments and electromagnetic simulations, we optimized the nanovilli structure as a SERS sensor. The sandwich-type aptasensor was designed using an aptamer and 4-Phenyl-1,2,4-triazoline-3,5-dione-methylene blue complex. The nanovilli-based aptasensor could sensitively detect various concentrations of 25-hydroxy vitamin D3, ranging from those found in deficient to excess conditions. The detection limit of the nanovilli-based sandwich-type aptasensor for 25-hydroxy vitamin D3 was 0.001 ng/mL, which is much lower than the deficiency concentration, and was detectable even in the human serum. In addition, our proposed sensor exhibited good repeatability (17.76%) and reproducibility (7.47%). Moreover, the nanovilli-based sandwich-type SERS aptasensor could selectively distinguish 25-hydroxy vitamin D3 from other vitamins. The silver nanovilli-based sandwich-type surface enhanced Raman scattering aptasensor opens a new avenue for the development of a bio-inspired vitamin-sensing platform.

A Magnetically Guided Self-Rolled Microrobot for Targeted Drug Delivery, Real-Time X-Ray Imaging, and Microrobot Retrieval.

Targeted drug delivery using a microrobot is a promising technique capable of overcoming the limitations of conventional chemotherapy that relies on body circulation. However, most studies of microrobots used for drug delivery have only demonstrated simple mobility rather than precise targeting methods and prove the possibility of biodegradation of implanted microrobots after drug delivery. In this study, magnetically guided self-rolled microrobot that enables autonomous navigation-based targeted drug delivery, real-time X-ray imaging, and microrobot retrieval is proposed. The microrobot, composed of a self-rolled body that is printed using focused light and a surface with magnetic nanoparticles attached, demonstrates the loading of doxorubicin and an X-ray contrast agent for cancer therapy and X-ray imaging. The microrobot is precisely mobilized to the lesion site through automated targeting using magnetic field control of an electromagnetic actuation system under real-time X-ray imaging. The photothermal effect using near-infrared light reveals rapid drug release of the microrobot located at the lesion site. After drug delivery, the microrobot is recovered without potential toxicity by implantation or degradation using a magnetic-field-switchable coiled catheter. This microrobotic approach using automated control method of the therapeutic agents-loaded microrobot has potential use in precise localized drug delivery systems.

Bioinspired Micro Glue Threads Fabricated by Liquid Bridge-to-Solidification as an Effective Sensing Platform.

Spiders synthesize their web using a liquid bridge-to-solidification mechanism at the end of their glands. Inspired by this process, in this work, we fabricated micro-glue threads (µGTs, polymer microwires) by a simple "pinch and spread" process using just two fingertips. The µGTs exhibited excellent tensile strength (∼50 GPa), comparable to those of spider silk and biological fibers. The chemical, physical, and mechanical properties of the µGTs were investigated, and it was confirmed that the thickness of the µGTs could be controlled by ethanol treatment in varying concentrations. Moreover, electrically conductive µGTs were easily fabricated by simply mixing them with various nanomaterials such as gold nanoparticles, zinc oxide nanowires, and reduced graphene oxide (rGO). Interestingly, the conductive µGTs, fabricated using rGO, exhibited remarkable electrical conductivity (0.45 µS) compared to those fabricated using other materials. The conductive µGTs are applicable not only to NO2 gas sensing but also as electrical fuselike materials that melt when the humidity increases. Collectively, the results present µGTs as cost-effective, simple, and versatile materials, which enables their application in a variety of sensors.

Nanophotonic Cell Lysis and Polymerase Chain Reaction with Gravity-Driven Cell Enrichment for Rapid Detection of Pathogens.

Rapid and precise detection of pathogens is a critical step in the prevention and identification of emergencies related to health and biosafety as well as the clinical management of community-acquired urinary tract infections or sexually transmitted diseases. However, a conventional culture-based pathogen diagnostic method is time-consuming, permitting physicians to use antibiotics without ample clinical data. Here, we present a nanophotonic Light-driven Integrated cell lysis and polymerase chain reaction (PCR) on a chip with Gravity-driven cell enrichment Health Technology (LIGHT) for rapid precision detection of pathogens (<20 min). We created the LIGHT, which has the three functions of (1) selective enrichment of pathogens, (2) photothermal cell lysis, and (3) photonic PCR on a chip. We designed the gravity-driven cell enrichment via a nanoporous membrane on a chip that allows an effective bacterial enrichment of 40 000-fold from a 1 mL sample in 2 min. We established a light-driven photothermal lysis of preconcentrated bacteria within 1 min by designing the network of nanoplasmonic optical antenna on a chip for ultrafast light-to-heat conversion, created the nanoplasmonic optical antenna network-based ultrafast photonic PCR on a chip, and identified Escherichia coli. Finally, we demonstrated the end-point detection of up to 103 CFU/mL of E. coli in 10 min. We believe that our nanophotonic LIGHT will provide rapid and precise identification of pathogens in both developing and developed countries.

Integrated Microalgae Analysis Photobioreactor for Rapid Strain Selection.

Algal photosynthesis is considered to be a sustainable, alternative, and renewable solution to generating green energy. For high-productivity algaculture in diverse local environments, a high-throughput screening method is needed to select algal strains from naturally available or genetically engineered strains. Herein, we present an integrated plasmonic photobioreactor for rapid, high-throughput screening of microalgae. Our 3D nanoplasmonic optical cavity-based photobioreactor permits the amplification of a selective wavelength favorable to photosynthesis in the cavity. The hemispheric plasmonic cavity allows intercellular interaction to be promoted in the optically favorable milieu and also permits effective visual examination of algal growth. Using Chlamydomonas reinhardtii, we demonstrated a 2-fold enhanced growth rate and a 1.5-fold lipid production rate with no distinctive lag phase. By facilitating growth and biomass conversion rates, the integrated microalgae analysis platform will serve as rapid microalgae screening platforms for biofuel applications.

A multistep photothermic-driven drug release system using wire-framed Au nanobundles.

Here, wire-framed Au nanobundles (WNBs), which consist of randomly oriented and mutually connected Au wires to form a bundle shape, are synthesized. In contrast to conventional nanoparticles (spheres, rods, cubes, and stars), which exhibit nanostructure only on the surface, cross-sectional view image shows that WNBs have nanostructures in a whole volume. By using this specific property of WNBs, an externally controllable multistep photothermic-driven drug release (PDR) system is demonstrated for in vivo cancer treatment. In contrast to conventional nanoparticles that encapsulate a drug on their surface, WNBs preserve the drug payload in the overall inner volume, providing a drug loading capacity sufficient for cancer therapy. An improved in vivo therapeutic efficacy of PDR therapy is also demonstrated by delivering sufficient amount of drugs to the target tumor region.

Label-free detection of zinc oxide nanowire using a graphene wrapping method.

Zinc oxide nanowires (ZnO NWs) have been attempted to various applications, such as piezoelectric devices, energy harvesting devices, self-powered nanosensors, and biomedical devices. However, recent reports have shown the toxic effect of ZnO NWs. In this report, we described the detection of ZnO NWs, for the first time using reduced graphene oxide (RGO) wrapping method. By wrapping RGO to ZnO NW (RGO-ZnO NW), we are able to aggregate ZnO NWs and increase the sensing performance. The detection measurement is based on the resonance frequency shift derived from mass variation of RGO-ZnO NW adsorption on the DNA immobilized resonator. The resonator is able to detect ZnO NWs with detection limit of 100 ng mL(-1) which is 2 order below the fatal toxic concentration of ZnO NWs in Human Monocyte Macrophages (HMMs). Furthermore, the resonator is able to detect ZnO NWs in real tap water, showing the potential as ZnO NWs screening platform in real environmental aqua system.

Multimodal label-free detection and discrimination for small molecules using a nanoporous resonator.

To detect chemical or biological threats, it is crucial that sensor devices can differentiate various target molecules. In general, each different sensing method has its own strengths and weaknesses due to their respective limitations. For example, although resonant sensors have high sensitivity, they are not able to discriminate target molecules. At the same time, although surface-enhanced Raman spectroscopy is a representative label-free detection method that can discriminate target molecules, its fabrication is often complex and expensive. Here we present a label-free multimodal nanoporous resonator-based system for small molecule detection and discrimination that combines the strengths of each of these sensing methods. Our approach is not only able to improve the sensitivity of the resonant sensor but it can also discriminate the target molecules. Furthermore, the fabrication process is swift (lasting <3 min) and convenient.