Three-dimensional (3D) molecular imaging enables the study of biological processes in both living and nonviable systems at the molecular level and has a high potential on early diagnosis. In conjunction with specific molecular probes, optical coherent tomography (OCT) is a promising imaging modality to provide 3D molecular features at the tissue level. In this study, we introduced (gold triangular nanoprism core)/(polyaniline shell) nanoparticles (GTNPs@PANI) as an OCT contrast agent and pH-responsive nanoprobe for 3D imaging of pH distribution. These core/shell nanoparticles possessed significantly different extinction and scattering properties in acidic and basic microenvironments. The switch of the optical features of the nanoparticles upon pH change was reversible, and the response time was less than 1.0 s. The nanoprobe successfully indicated the acid regions of a mimic tumor from the basic region in a gelatin-based phantom under OCT imaging. As a demonstration of practical applications, real-time 3D OCT imaging of pH and lactic acid in the anterior chamber of a fish eye was realized by GTNPs@PANI nanoparticles. Using GTNPs@PANI nanoparticles as the contrast probes for OCT imaging, noninvasive and real-time molecular imaging in both living and nonviable systems at the microscale can be achieved.

Ozone (O3) would be harmful to human skin for its strong oxidizing property, especially when stratum corneum or corneal epithelium is wounded. Imaging the penetration and distribution of ozone at depth is beneficial for studying the influence of ozone on skin or eyes. Here, we introduced a facile method for three-dimensional (3D) imaging of the penetration of O3 into the anterior chamber of an isolated crucian carp eye by using optical coherence tomography (OCT) combined with gold triangular nanoprisms (GTNPs) as the contrast agent and molecular probe. We illustrated the specific response of GTNPs to ozone and demonstrated that GTNPs can function as an efficient nanoprobe for sensing O3. The stabilities of GTNPs in different biologic solutions, as well as the signal intensity of GTNPs on an OCT imaging system, were investigated. Visualization of 3D penetration and distribution of O3 in the biologic tissue was proved for the first time. The quantitative analysis of O3 diffusion in the anterior chamber of the fish eye revealed a penetration depth of 311 μm within 172 min. Due to the strong scattering, near-infrared extinction band, and easy functionalization of GTNPs, they could further serve as nanoprobes for 3D OCT or multimodal imaging of other molecules or ions in the future.

•The Al nanopyramid arrays (NPAs) are applied for one-step detection of carbohydrate antigen 199.•The measurements are performed in air, which are convenient and sensitive.•Plasmons distributed across the whole UV–vis-IR region exhibited on one substrate were observed for the first time.•The refractive index (RI) sensitivity of the as-prepared Al NPA may be the highest RI sensitivity of aluminum LSPRs demonstrated so far.•The uniform quasi-3-dimensional NPA structure can be prepared in large-area with a simple, cost-effective manner.Aluminum-based localized surface plasmon resonance (LSPR) holds attractive properties include low cost, high natural abundance, and ease of processing by a wide variety of methods including complementary metal oxide semiconductor process, making itself having an edge over conventional ones induced by noble metal. However, the inherent drawbacks of plasmonic mode limited on UV–green wavelength, low refractive index sensitivity, as well as heavy-shape-dependence greatly prevent aluminum plasmonics from real-life biosensing. Here, we demonstrated a uniform quasi-3-dimensional Al nanopyramid array (NPA) structure with tunable ultraviolet–visible–infrared (UV–vis–NIR) plasmon resonances for biosensing. By changing the reflection measuring angle, we could easily obtain typical peaks simultaneously exhibited on the reflectance spectrum across UV–vis–NIR wave region. The Al NPAs carried out high refractive index sensitivities which even comparable with that of noble metal, and can be used as a biosensor for directly detecting cytochrome c and carbohydrate antigen 199 in air after the sensing surface was washed cleanly and dried; the limits of detection were determined to be 800 nM and 29 ng/mL, respectively. Our proposed work therefore initiates the low-cost, high-performance biosensing using aluminum plasmonics, which would find wide applications in rapid diagnosis, mobile-healthcare and environmental monitoring.

In this paper, we fabricated uniform polydimethylsiloxane (PDMS) magnetic microcapsules with eccentric internal structures and employed them as a novel delivery system for orientation-specific and dual stimuli-responsive controlled drug release. These eccentric microcapsules contained Fe3O4 nanoparticles in their inner cores. Because of the paramagnetic Fe3O4 nanoparticles, the eccentric microcapsules could be accurately moved by a magnetic field, leading to the precise control of the microcapsule locations. Also, due to the eccentric structures of the magnetic microcapsules, the capsules exhibited a non-uniform magnetic property; the capsules could be aligned by magnetic fields with their thin walls facing the magnet, resulting in a precise orientation-specific control of the microcapsules. More interestingly, the eccentric magnetic microcapsules demonstrated a dual stimuli-responsive controlled release of inclusions involving a sustained release under ultrasound and an intense release under laser stimulation. Furthermore, we studied the efficacy of doxorubicin (DOX) release from the microcapsules regulated by laser stimulation by performing in vitro cell tests with and without an applied magnetic field. The cell tests showed that the orientation-specific control of the microcapsules under a magnetic field (when the thin walls of the eccentric microcapsules were oriented towards the cell) improved the efficacy of the drug released from the microcapsules. The results suggested that our eccentric magnetic microcapsules hold all the properties needed for a site-specific, orientation-specific and dual stimuli-responsive delivery system, demonstrating a great potential application for multifunctional controlled drug release.

Localized surface plasmon resonance (LSPR) can concentrate light into nanometer-scale spatial regions, which increases the sensitivity to local refractive index changes in response to the presence of analytes on or near metal surfaces. LSPR-based nanostructured materials have great potential for being developed into large-scale arrays composed of highly miniaturized and uniform signal transducer elements, thus initiating high throughput screening platforms for refractometric biosensing. In this review, we present an overview of nanostructured materials with LSPRs and their applications in biosensing. First, we give a fundamental and practical introduction of the study of localized surface plasmon excitations in metal materials, and then focus on some well-designed nanostructures, in particular on thin perforated films and some quasi-three-dimensional structures. Each nanostructure is detailed and their plasmonic properties are briefly described. Subsequently, a brief summary of the fabrication methods for plasmonic nanostructures are presented. Finally, the future research trends of plasmonic biosensing are highlighted and a conclusion with perspectives is given.

Tuning the localized surface plasmon modes of gold nanostructures to be in resonance with near-infrared incident light is desirable in various applications such as biosensing, biomedicine/therapy and opto-electronic devices. Unfortunately, current methods for regulating the plasmon modes of gold nanoparticles still suffer from poor controllability and reproducibility. Here, we developed a facile and effective method to precisely tailor the plasmon mode of gold triangular nanoprisms (GTNPs) by simply exposing them to O3 atmosphere. The resonant wavelength of the plasmon mode sustained by the GTNPs can be steadily tuned over a broad spectral range varying from 1010 nm to 780 nm (within the bio-window region), along with their shapes gradually changing from triangular nanoprism into circular nanoplate. By controlling the concentrations of O3, exposure duration, the concentrations of surfactant in suspension and the reaction temperature, GTNPs with various plasmon modes could be efficiently obtained from one original GTNPs sample. To demonstrate the potential applications of these GTNPs, we applied this method to obtain gold nanoplates as-needed for enhanced optical coherence tomography (OCT) and photothermal therapy. The plasmon mode of GTNPs was tuned to match the excitation wavelength of the OCT laser source, and was applied to enhance the signal of OCT imaging. The plasmon mode of GTNPs was also precisely tuned to 808 nm which was well resonant with the wavelength of a near-infrared excitation laser (λex = 808 nm); when the as-obtained GTNPs were used as a photothermal agent, they displayed an enhanced effect of photothermal therapy on Hela cancer cells compared to those without the tuning of the plasmon mode. Considering the simplicity and high controllability of the method for fine-tuning the plasmonic mode of GTNPs, this work has great potential in a wide range of applications such as biomedical imaging and thermotherapy, chemical/biological sensing, surface-enhanced spectroscopy and solar energy harvesting, etc.

A plasmonic gold nanomushroom array (GNMA), whose figure of merit (FOM) is close to the theoretically predicted upper limit for standard propagating surface plasmon resonance (PSPR) sensors, made the biosensing performance of this type of LSPR sensor comparable to that of commercial PSPR sensors. However, for commercial implementation of GNMA sensors, a low-cost fabrication method and a simple optical measurement scheme are both urgently required. Herein, we introduce elastic soft lithography to replicate GNMAs with uniform shapes and sizes. This approach is low-cost, facile and reproducible, and might be suitable for industrial production of a mushroom nanopillar array whose tops are larger than their middles. The as-obtained GNMAs consisting of a transparent substrate were applied to convenient normal transmission measurements, and showed excellent refractive index sensitivity and FOM value. Notably, four medical analytes were simultaneously detected on a microarray chip integrated with a GNMA sensing component, suggesting that the GNMA sensing substrate is a promising candidate for high-throughput monitoring of multiple analytes.

•A novel method of laser carving under ice layer without laser energy attenuation is proposed.•The accuracy of machined channel width would not be affected at the condition of laser carving under ice.•A thermal effect model of laser beam on ice layer and workpiece is developed.•The recast layer and dross is well removed.•High temperature influence area, heat effect zone and surface oxidation are decreased.A novel method of fiber laser carving machining under ice layer without laser energy attenuation was proposed to reduce workpiece defects such as recast layer, dross, high temperature influence area, surface oxidation and heat effect zone that were typically found in machining in air. The mechanism of laser carving process under ice was analyzed to understand the thermal effect of laser pulse on the ice layer and workpiece. A cooling module based on Peltier cooler was designed to form an ice layer on the surface of workpiece. To investigate the effect of ice layer, the laser carving under ice and in air on titanium, red copper and aluminum workpiece were conducted. The results showed that the ice layer attenuated the laser energy barely resulting that the accuracy of machined channel width would not be affected at the condition of laser carving under ice. The recast layer and dross along the machined channel could be well removed. The high temperature influence area, heat effect and surface oxidation could also be decreased. It is due to that the ice isolated the ejective molten material and oxygen from the surface of workpiece and provided a rapid cooling rate.

•The gold nano-mushroom arrays (GNMA) functionalized with antibody were well characterized.•The GNMAs enabled label-free and one-step detection of alpha-fetoprotein in human serum.•The measurements are performed in air, which are convenient and sensitive.•The GNMAs with lifted-up gold nanocaps showed great potential for quantitative detection.•The GNMAs initiated rapid detection and high-throughput screening on microfluidic chips.Localized surface plasmon resonance (LSPR) combined with immunoassay shows greatly potential in fast detection of tumor markers. In this paper, a highly sensitive LSPR substrate has been fabricated and modified for direct detection of alpha-fetoprotein (AFP). The biosensor was prepared by interference lithography, and modified by covalently immobilizing anti-AFP on the surface of gold nano-mushroom arrays (GNMA). The modification process was investigated by Vis–NIR reflectance spectra and cyclic voltammogram measurements. We revealed the optical properties of the modified GNMA by measuring the Vis–NIR reflectance spectra and simulating its electric intensity field distribution under light illumination. The GNMA substrate was highly sensitive, with a refractive index sensitivity of ~465 nm/RIU. The substrate can be applied to label-free detection of AFP, with the linear range and the limit of detection determined to be 20–200 ng/mL and 24 ng/mL (S/N=3), respectively. We also demonstrated its clinical application by directly detecting AFP in human serum samples. It is expected that our biosensor could be integrated on microfluidic chips for high-throughput detection in portable early diagnosis, post-operative and point-of-care (POC) in clinical applications.

In this paper, a strategy was developed for fabricating uniform polydimethylsiloxane (PDMS) microcapsules with eccentric and core-centered internal hollow structures, which can be employed as a novel controlled-release system for site-specific drug delivery under ultrasound regulation. This strategy involves the use of a microfluidic device, through which three phases (i.e., an inner water phase containing drug molecules, a middle oil phase of PDMS solution, and an outer water phase) were delivered at independently adjustable flow rates, allowing the formation of water-in-oil-in-water (W/O/W) emulsion droplets in a microfluidic device. After baking the as-prepared microcapsules, microcapsules with different inner hollow cores were obtained. The sizes of the inner hollow structures could be tuned, leading to a series of microcapsules with different densities. The densities of these microcapsules were all lower than that of water, which showed a long gastric residence time. Most interestingly, eccentric hollow microcapsules with well-controlled sizes and shapes were also prepared using this method. The eccentric and core-centered hollow microcapsules demonstrated triggered and controlled the release of encapsulation under ultrasound, for which the release profiles were consistent with the theoretical simulation. The results showed that the microcapsules had all the properties of a floating drug delivery system and controlled release system, and demonstrated great potential to be used for controlled release, in particular, for the delivery of drugs that are absorbed primarily in the upper segments of the gastrointestinal tract.

In this paper, a strategy was developed for fabricating uniform polydimethylsiloxane (PDMS) microcapsules with eccentric and core-centered internal hollow structures, which can be employed as a novel controlled-release system for site-specific drug delivery under ultrasound regulation. This strategy involves the use of a microfluidic device, through which three phases (i.e., an inner water phase containing drug molecules, a middle oil phase of PDMS solution, and an outer water phase) were delivered at independently adjustable flow rates, allowing the formation of water-in-oil-in-water (W/O/W) emulsion droplets in a microfluidic device. After baking the as-prepared microcapsules, microcapsules with different inner hollow cores were obtained. The sizes of the inner hollow structures could be tuned, leading to a series of microcapsules with different densities. The densities of these microcapsules were all lower than that of water, which showed a long gastric residence time. Most interestingly, eccentric hollow microcapsules with well-controlled sizes and shapes were also prepared using this method. The eccentric and core-centered hollow microcapsules demonstrated triggered and controlled the release of encapsulation under ultrasound, for which the release profiles were consistent with the theoretical simulation. The results showed that the microcapsules had all the properties of a floating drug delivery system and controlled release system, and demonstrated great potential to be used for controlled release, in particular, for the delivery of drugs that are absorbed primarily in the upper segments of the gastrointestinal tract.

Localized surface plasmon resonance (LSPR) can concentrate light into nanometer-scale spatial regions, which increases the sensitivity to local refractive index changes in response to the presence of analytes on or near metal surfaces. LSPR-based nanostructured materials have great potential for being developed into large-scale arrays composed of highly miniaturized and uniform signal transducer elements, thus initiating high throughput screening platforms for refractometric biosensing. In this review, we present an overview of nanostructured materials with LSPRs and their applications in biosensing. First, we give a fundamental and practical introduction of the study of localized surface plasmon excitations in metal materials, and then focus on some well-designed nanostructures, in particular on thin perforated films and some quasi-three-dimensional structures. Each nanostructure is detailed and their plasmonic properties are briefly described. Subsequently, a brief summary of the fabrication methods for plasmonic nanostructures are presented. Finally, the future research trends of plasmonic biosensing are highlighted and a conclusion with perspectives is given.

In this paper, we fabricated uniform polydimethylsiloxane (PDMS) magnetic microcapsules with eccentric internal structures and employed them as a novel delivery system for orientation-specific and dual stimuli-responsive controlled drug release. These eccentric microcapsules contained Fe3O4 nanoparticles in their inner cores. Because of the paramagnetic Fe3O4 nanoparticles, the eccentric microcapsules could be accurately moved by a magnetic field, leading to the precise control of the microcapsule locations. Also, due to the eccentric structures of the magnetic microcapsules, the capsules exhibited a non-uniform magnetic property; the capsules could be aligned by magnetic fields with their thin walls facing the magnet, resulting in a precise orientation-specific control of the microcapsules. More interestingly, the eccentric magnetic microcapsules demonstrated a dual stimuli-responsive controlled release of inclusions involving a sustained release under ultrasound and an intense release under laser stimulation. Furthermore, we studied the efficacy of doxorubicin (DOX) release from the microcapsules regulated by laser stimulation by performing in vitro cell tests with and without an applied magnetic field. The cell tests showed that the orientation-specific control of the microcapsules under a magnetic field (when the thin walls of the eccentric microcapsules were oriented towards the cell) improved the efficacy of the drug released from the microcapsules. The results suggested that our eccentric magnetic microcapsules hold all the properties needed for a site-specific, orientation-specific and dual stimuli-responsive delivery system, demonstrating a great potential application for multifunctional controlled drug release.