From Single‐Dimensional to Multidimensional Manipulation of Optical Waves with Metasurfaces

Metasurfaces, 2D artificial arrays of subwavelength elements, have attracted great interest from the optical scientific community in recent years because they provide versatile possibilities for the manipulation of optical waves and promise an effective way for miniaturization and integration of optical devices. In the past decade, the main efforts were focused on the realization of single‐dimensional (amplitude, frequency, polarization, or phase) manipulation of optical waves. Compared to the metasurfaces with single‐dimensional manipulation, metasurfaces with multidimensional manipulation of optical waves show significant advantages in many practical application areas, such as optical holograms, sub‐diffraction imaging, and the design of integrated multifunctional optical devices. Nowadays, with the rapid development of nanofabrication techniques, the research of metasurfaces has been inevitably developed from single‐dimensional manipulation toward multidimensional manipulation of optical waves, which greatly boosts the application of metasurfaces and further paves the way for arbitrary design of optical devices. Herein, the recent advances in metasurfaces are briefly reviewed and classified from the viewpoint of different dimensional manipulations of optical waves. Single‐dimensional manipulation and 2D manipulation of optical waves with metasurfaces are discussed systematically. In conclusion, an outlook and perspectives on the challenges and future prospects in these rapidly growing research areas are provided.     

Manipulation of live mouse embryonic stem cells using holographic optical tweezers

We report the ability to move and arrange patterns of live embryonic stem cells using holographic optical tweezers. Single cell suspensions of mouse embryonic stem cells were manipulated with holographic optical tweezers into a variety of patterns including lines, curves and circles. Individual cells were also lifted out of the sample plane highlighting the potential for 3D positional control. Trypan blue dye exclusion and Live/Dead? staining (CMFDA^?1, EthHD^?1) showed that the cells were still viable after manipulation with the optical tweezers. The ability to move individual stem cells into specific, pre-defined patterns provides a method to study how arrangement and associated small-scale interactions occur between neighbouring cells.     

Near‐Infrared Light‐Sensitive Polyvinyl Alcohol Hydrogel Photoresist for Spatiotemporal Control of Cell‐Instructive 3D Microenvironments

Advanced hydrogel systems that allow precise control of cells and their 3D microenvironments are needed in tissue engineering, disease modeling, and drug screening. Multiphoton lithography (MPL) allows true 3D microfabrication of complex objects, but its biological application requires a cell‐compatible hydrogel resist that is sufficiently photosensitive, cell‐degradable, and permissive to support 3D cell growth. Here, an extremely photosensitive cell‐responsive hydrogel composed of peptide‐crosslinked polyvinyl alcohol (PVA) is designed to expand the biological applications of MPL. PVA hydrogels are formed rapidly by ultraviolet light within 1 min in the presence of cells, providing fully synthetic matrices that are instructive for cell‐matrix remodeling, multicellular morphogenesis, and protease‐mediated cell invasion. By focusing a multiphoton laser into a cell‐laden PVA hydrogel, cell‐instructive extracellular cues are site‐specifically attached to the PVA matrix. Cell invasion is thus precisely guided in 3D with micrometer‐scale spatial resolution. This robust hydrogel enables, for the first time, ultrafast MPL of cell‐responsive synthetic matrices at writing speeds up to 50 mm s^?1. This approach should enable facile photochemical construction and manipulation of 3D cellular microenvironments with unprecedented flexibility and precision.     

Parallel Preparation of Densely Packed Arrays of 150‐nm Gold‐Nanocrescent Resonators in Three Dimensions

Metallic nanostructures show interesting optical properties due to their plasmonic resonances, and when arranged in three‐dimensional (3D) arrays hold promise for optical metamaterials with negative refractive index. Towards this goal a simple, cheap, and parallel method to fabricate large‐area, ordered arrays of 150‐nm gold nanocrescents supporting plasmonic resonances in the near‐infrared spectral range is demonstrated. In this process hexagonally ordered monolayers of monodisperse colloids are prepared by a simple floating technique, and subsequently the individual particles are size‐reduced in a plasma process and used as a shadow mask with the initial lattice spacing. The resulting two‐dimensional array of plasmonic resonators is coated with a transparent silica layer, which serves as a support for a second layer prepared by the identical process. The mutual orientation of the nanostructures between the individual layers can be freely adjusted, which determines the polarization‐dependent absorption of the array and opens the possibility to introduce chirality in this type of 3D metamaterial. The iteration of this simple and efficient methodology yields 3D arrays with optical features as sharp as those of the individual nanocrescents, and shows strong potential for large‐scale production of high‐quality optical metamaterials.     

Surface‐Acoustic‐Wave‐Based Lab‐on‐Chip for Rapid Transport of Cryoprotectants across Cell Membrane for Cryopreservation with Significantly Improved Cell Viability

Cryopreservation is essential to effectively extend the shelf life of delicate biomaterials while maintaining proper levels of cell functions. Cryopreservation requires a cryoprotective agent (CPA) to suppress intracellular ice formation during freezing, but it must be removed prior to clinical use due to its toxicity. Conventional multistep CPA loading and unloading approaches are time consuming, often creating osmotic shocks and causing mechanical injuries for biological samples. An efficient surface‐acoustic‐wave‐ (SAW‐) based lab‐on‐a‐chip (LoC) for fast loading and removal of CPAs is presented here. With the SAW‐based multistep CPA loading/removal approach, high concentration (3 m ) CPA can be successfully loaded and removed in less than 1 min. Results show that the technique causes the least harm to umbilical cord matrix mesenchymal stem cells as compared to conventional method, and an average of 24% higher cell recovery rate is achieved, while preserving the integrity and morphology of the cells. This device is the first of its kind to combine high loading/unloading efficiency, high cell viability, and high throughput into one LoC device, offering not only a more efficient and safer route for CPA loading and removal from cells, but also paving the way for other cryopreservation‐dependent applications.     

Single‐Cell Biodetection by Upconverting Microspinners

Near‐infrared‐light‐mediated optical tweezing of individual upconverting particles has enabled all‐optical single‐cell studies, such as intracellular thermal sensing and minimally invasive cytoplasm investigations. Furthermore, the intrinsic optical birefringence of upconverting particles renders them light‐driven luminescent spinners with a yet unexplored potential in biomedicine. In this work, the use of upconverting spinners is showcased for the accurate and specific detection of single‐cell and single‐bacteria attachment events, through real‐time monitoring of the spinners rotation velocity of the spinner. The physical mechanisms linking single‐attachment to the angular deceleration of upconverting spinners are discussed in detail. Concomitantly, the upconversion emission generated by the spinner is harnessed for simultaneous thermal sensing and thermal control during the attachment event. Results here included demonstrate the potential of upconverting particles for the development of fast, high‐sensitivity, and cost‐effective systems for single‐cell biodetection.     

Cancer‐Cell‐Phenotype‐Dependent Differential Intracellular Trafficking of Unconjugated Quantum Dots

A diverse array of nanoparticles, including quantum dots (QDs), metals, polymers, liposomes, and dendrimers, are being investigated as therapeutics and imaging agents in cancer diseases. However, the role of the cancer‐cell phenotype on the uptake and intracellular fate of nanoparticles in cancer cells remains poorly understood. Reported here is that differences in cancer‐cell phenotypes can lead to significant differences in intracellular sorting, trafficking, and localization of nanoparticles. Unconjugated anionic QDs demonstrate dramatically different intracellular profiles in three closely related human‐prostate‐cancer cells used in the investigation: PC3, PC3‐flu, and PC3‐PSMA. QDs demonstrate punctated intracellular localization throughout the cytoplasm in PC3 cells. In contrast, the nanoparticles localize mainly at a single juxtanuclear location (“dot‐of‐dots”) inside the perinuclear recycling compartment in PC3‐PSMA cells, where they co‐localize with transferrin and the prostate‐specific membrane antigen. The results indicate that nanoparticle sorting and transport is influenced by changes in cancer‐cell phenotype and can have significant implications in the design and engineering of nanoscale drug delivery and imaging systems for advanced tumors.     

Preparation and Characterization of Dentin Phosphophoryn‐Derived Peptide‐Functionalized Lignin Nanoparticles for Enhanced Cellular Uptake

The surface modification of nanoparticles (NPs) using different ligands is a common strategy to increase NP?cell interactions. Here, dentin phosphophoryn‐derived peptide (DSS) lignin nanoparticles (LNPs) are prepared and characterized, the cellular internalization of the DSS‐functionalized LNPs (LNPs‐DSS) into three different cancer cell lines is evaluated, and their efficacy with the widely used iRGD peptide is compared. It is shown that controlled extent of carboxylation of lignin improves the stability at physiological conditions of LNPs formed upon solvent exchange. Functionalization with DSS and iRGD peptides maintains the spherical morphology and moderate polydispersity of LNPs. The LNPs exhibit good cytocompatibility when cultured with PC3‐MM2, MDA‐MB‐231, and A549 in the conventional 2D model and in the 3D cell spheroid morphology. Importantly, the 3D cell models reveal augmented internalization of peptide‐functionalized LNPs and improve antiproliferative effects when the LNPs are loaded with a cytotoxic compound. Overall, LNPs‐DSS show equal or even superior cellular internalization than the LNPs‐iRGD, suggesting that DSS can also be used to enhance the cellular uptake of NPs into different types of cells, and release different cargos intracellularly.     

A Monolithic Force‐Sensitive 3D Microgripper Fabricated on the Tip of an Optical Fiber Using 2‐Photon Polymerization

Microscale robotic devices have myriad potential applications including drug delivery, biosensing, cell manipulation, and microsurgery. In this work, a tethered, 3D, compliant grasper with an integrated force sensor is presented, the entirety of which is fabricated on the tip of an optical fiber in a single‐step process using 2‐photon polymerization. This gripper can prove useful for the interrogation of biological microstructures such as alveoli, villi, or even individual cells. The position of the passively actuated grasper is controlled via micromanipulation of the optical fiber, and the microrobotic device measures approximately 100 µm in length and breadth. The force estimation is achieved using optical interferometry: high‐dimensional spectral readings are used to train artificial neural networks to predict the axial force exerted on/by the gripper. The design, characterization, and testing of the grasper are described and its real‐time force‐sensing capability with an accuracy below 2.7% of the maximum calibrated force is demonstrated.     

In‐Plane Isotropic/Anisotropic 2D van der Waals Heterostructures for Future Devices

Mono‐ to few‐layers of 2D semiconducting materials have uniquely inherent optical, electronic, and magnetic properties that make them ideal for probing fundamental scientific phenomena up to the 2D quantum limit and exploring their emerging technological applications. This Review focuses on the fundamental optoelectronic studies and potential applications of in‐plane isotropic/anisotropic 2D semiconducting heterostructures. Strong light–matter interaction, reduced dimensionality, and dielectric screening in mono‐ to few‐layers of 2D semiconducting materials result in strong many‐body interactions, leading to the formation of robust quasiparticles such as excitons, trions, and biexcitons. An in‐plane isotropic nature leads to the quasi‐2D particles, whereas, an anisotropic nature leads to quasi‐1D particles. Hence, in‐plane isotropic/anisotropic 2D heterostructures lead to the formation of quasi‐1D/2D particle systems allowing for the manipulation of high binding energy quasi‐1D particle populations for use in a wide variety of applications. This Review emphasizes an exciting 1D–2D particles dynamic in such heterostructures and their potential for high‐performance photoemitters and exciton–polariton lasers. Moreover, their scopes are also broadened in thermoelectricity, piezoelectricity, photostriction, energy storage, hydrogen evolution reactions, and chemical sensor fields. The unique in‐plane isotropic/anisotropic 2D heterostructures may open the possibility of engineering smart devices in the nanodomain with complex opto‐electromechanical functions.     

Digital holographic microscopy with reduced spatial coherence for three-dimensional particle flow analysis

We investigate the use of a digital holographic microscope working in partially coherent illumination to study in three dimensions a micrometer-size particle flow. The phenomenon under investigation rapidly varies in such a way that it is necessary to record, for every camera frame, the complete holographic information for further processing. For this purpose, we implement the Fourier-transform method for optical amplitude extraction. The suspension of particles is flowing in a split-flow lateral-transport thin separation cell that is usually used to separate the species by their sizes. Details of the optical implementation are provided. Examples of reconstructed images of different particle sizes are shown, and a particle-velocity measurement technique that is based on the blurred holographic image is exploited.     

High‐Speed 3D Printing of Millimeter‐Size Customized Aspheric Imaging Lenses with Sub 7 nm Surface Roughness

Advancements in three‐dimensional (3D) printing technology have the potential to transform the manufacture of customized optical elements, which today relies heavily on time‐consuming and costly polishing and grinding processes. However the inherent speed‐accuracy trade‐off seriously constrains the practical applications of 3D‐printing technology in the optical realm. In addressing this issue, here, a new method featuring a significantly faster fabrication speed, at 24.54 mm³ h^?1, without compromising the fabrication accuracy required to 3D‐print customized optical components is reported. A high‐speed 3D‐printing process with subvoxel‐scale precision (sub 5 µm) and deep subwavelength (sub 7 nm) surface roughness by employing the projection micro‐stereolithography process and the synergistic effects from grayscale photopolymerization and the meniscus equilibrium post‐curing methods is demonstrated. Fabricating a customized aspheric lens 5 mm in height and 3 mm in diameter is accomplished in four hours. The 3D‐printed singlet aspheric lens demonstrates a maximal imaging resolution of 373.2 lp mm^?1 with low field distortion less than 0.13% across a 2 mm field of view. This lens is attached onto a cell phone camera and the colorful fine details of a sunset moth's wing and the spot on a weevil's elytra are captured. This work demonstrates the potential of this method to rapidly prototype optical components or systems based on 3D printing.     

Tweezing of Magnetic and Non‐Magnetic Objects with Magnetic Fields

Although strong magnetic fields cannot be conveniently “focused” like light, modern microfabrication techniques enable preparation of microstructures with which the field gradients – and resulting magnetic forces – can be localized to very small dimensions. This ability provides the foundation for magnetic tweezers which in their classical variant can address magnetic targets. More recently, the so‐called negative magnetophoretic tweezers have also been developed which enable trapping and manipulations of completely nonmagnetic particles provided that they are suspended in a high‐magnetic‐susceptibility liquid. These two modes of magnetic tweezing are complimentary techniques tailorable for different types of applications. This Progress Report provides the theoretical basis for both modalities and illustrates their specific uses ranging from the manipulation of colloids in 2D and 3D, to trapping of living cells, control of cell function, experiments with single molecules, and more.     

Alkyl‐Capped Silicon Nanocrystals Lack Cytotoxicity and have Enhanced Intracellular Accumulation in Malignant Cells via Cholesterol‐Dependent Endocytosis

Nanocrystals of various inorganic materials are being considered for application in the life sciences as fluorescent labels and for such therapeutic applications as drug delivery or targeted cell destruction. The potential applications of the nanoparticles are critically compromised due to the well‐documented toxicity and lack of understanding about the mechanisms involved in the intracellular internalization. Here intracellular internalization and toxicity of alkyl‐capped silicon nanocrystals in human neoplastic and normal primary cells is reported. The capped nanocrystals lack cytotoxicity, and there is a marked difference in the rate and extent of intracellular accumulation of the nanoparticles between human cancerous and non‐cancerous primary cells, the rate and extent being higher in the malignant cells compared to normal human primary cells. The exposure of the cells to the alkyl‐capped nanocrystals demonstrates no evidence of in vitro cytotoxicity when assessed by cell morphology, apoptosis, and cell viability assays. The internalization of the nanocrystals by Hela and SW1353 cells is almost completely blocked by the pinocytosis inhibitors filipin, cytochalasin B, and actinomycin D. The internalization process is not associated with any surface change in the nanoparticles, as their luminescence spectrum is unaltered upon transport into the cytosol. The observed dramatic difference in the rate and extent of internalization of the nanocrystals between malignant and non‐malignant cells therefore offers potential application in the management of human neoplastic conditions.     

Hierarchical Hydrogen Bonds Directed Multi‐Functional Carbon Nanotube‐Based Supramolecular Hydrogels

Supramolecular hydrogels (SMHs) are three‐dimensional networks filled with a large amount of water. The crosslinking force in the 3D network is always constructed by relatively weak and dynamic non‐covalent interactions, and thus SMHs usually possess extremely high susceptibility to external environment and can show extraordinary stimuli‐responsive, self‐healing or other attractive properties. However, the overall crosslinking force in hydrogel networks is difficult to flexibly modulate, and this leads to limited functions of the SMHs. In this regard, hierarchical hydrogen bonds, that is, the mixture of relatively strong and relatively weak hydrogen bonds, are used herein as crosslinking force for the hydrogel preparation. The ratio of strong and weak hydrogen bonds can be finely tuned to tailor the properties of resultant gels. Thus, by delicate manipulation of the overall crosslinking force in the system, a hydrogel with multiple (thermal, pH and NIR light) responsiveness, autonomous self‐healing property and interesting temperature dependent, reversible adhesion behavior is obtained. This kind of hierarchical hydrogen bond manipulation is proved to be a general method for multiple‐functionality hydrogel preparation, and the resultant material shows potential for a range of applications.     

Multifarious Transit Gates for Programmable Delivery of Bio‐functionalized Matters

Programmable delivery of biological matter is indispensable for the massive arrays of individual objects in biochemical and biomedical applications. Although a digital manipulation of single cells has been implemented by the integrated circuits of micromagnetophoretic patterns with current wires, the complex fabrication process and multiple current operation steps restrict its practical application for biomolecule arrays. Here, a convenient approach using multifarious transit gates is proposed, for digital manipulation of biofunctionalized microrobotic particles that can pass through the local energy barriers by a time‐dependent pulsed magnetic field instead of multiple current wires. The multifarious transit gates including return, delay, and resistance linear gates, as well as dividing, reversed, and rectifying T‐junction gates, are investigated theoretically and experimentally for the programmable manipulation of microrobotic particles. The results demonstrate that, a suitable angle of the gating field at a suitable time zone is crucial to implement digital operations at integrated multifarious transit gates along bifurcation paths to trap microrobotic particles in specific apartments, paving the way for flexible on‐chip arrays of biomolecules and cells.     

Multichannel‐Independent Information Encoding with Optical Metasurfaces

Optical metasurfaces, as an emerging platform, have been shown to be capable of effectively manipulating the local properties (amplitude, phase, and polarization) of the reflected or transmitted light and have unique strengths in high‐density optical storage, holography, display, etc. The reliability and flexibility of wavefront manipulation makes optical metasurfaces suitable for information encryption by increasing the possibility of encoding combinations of independent channels and the capacity of encryption, and thus the security level. Here, recent progress in metasurface‐based information encoding is reviewed, in which the independent channels for information encoding are built with wavelength and/or polarization in one‐dimensional/two‐dimensional (1D/2D) modes. The way to increase information encoding capacity and security level is proposed, and the opportunities and challenges of information encoding with independent channels based on metasurfaces are discussed.     

Synthesis of Colloidal SU‐8 Polymer Rods Using Sonication

The bulk synthesis of fluorescent colloidal SU‐8 polymer rods with tunable dimensions is described. The colloidal SU‐8 rods are prepared by shearing an emulsion of SU‐8 polymer droplets and then exposing the resulting non‐Brownian rods to ultrasonic waves, which breaks them into colloidal rods with typical lengths of 3.5–10 µm and diameters of 0.4–1 µm. The rods are stable in both aqueous and apolar solvents, and by varying the composition of apolar solvent mixtures both the difference in refractive index and mass density between particles and solvent can be independently controlled. Consequently, these colloidal SU‐8 rods can be used in both 3D confocal microscopy and optical trapping experiments while carefully tuning the effect of gravity. This is demonstrated by using confocal microscopy to image the liquid crystalline phases and the isotropic–nematic interface formed by the colloidal SU‐8 rods and by optically trapping single rods in water. Finally, the simultaneous confocal imaging and optical manipulation of multiple SU‐8 rods in the isotropic phase is shown.     

Rapid,High‐Throughput,and Direct Molecular Beacon Delivery to Human Cancer Cells Using a Nanowire‐Incorporated and Pneumatic Pressure‐Driven Microdevice

Tracking and monitoring the intracellular behavior of mRNA is of paramount importance for understanding real‐time gene expression in cell biology. To detect specific mRNA sequences, molecular beacons (MBs) have been widely employed as sensing probes. Although numerous strategies for MB delivery into the target cells have been reported, many issues such as the cytotoxicity of the carriers, dependence on the random probability of MB transfer, and critical cellular damage still need to be overcome. Herein, we have developed a nanowire‐incorporated and pneumatic pressure‐driven microdevice for rapid, high‐throughput, and direct MB delivery to human breast cancer MCF‐7 cells to monitor survivin mRNA expression. The proposed microdevice is composed of three layers: a pump‐associated glass manifold layer, a monolithic polydimethylsiloxane (PDMS) membrane, and a ZnO nanowire‐patterned microchannel layer. The MB is immobilized on the ZnO nanowires by disulfide bonding, and the glass manifold and PDMS membrane serve as a microvalve, so that the cellular attachment and detachment on the MB‐coated nanowire array can be manipulated. The combination of the nanowire‐mediated MB delivery and the microvalve function enable the transfer of MB into the cells in a controllable way with high cell viability and to detect survivin mRNA expression quantitatively after docetaxel treatment.     

Three‐dimensional Displacement and Shape Measurement with a Diffraction‐assisted Grid Method

The grid method is a full‐field optical technique for computing surface displacements and strains of a material by analyzing the phase of grid lines patterned on the specimen. To date, most experiments using the grid method have measured only two‐dimensional in‐plane deformations. Here, the grid method is extended to three dimensions by using a crossed grid pattern and a diffraction grating which enables acquiring images from multiple viewing angles on a single camera. In‐plane displacements and strains are computed using the conventional grid method, and the corresponding three‐dimensional (3D) displacements—including out‐of‐plane displacements or shapes—are computed by analyzing the images collected at different viewing angles. The technique is demonstrated by measuring 3D rigid body motion, the 3D displacements of a membrane in a pressure‐bulge experiment, and the out‐of‐plane curvature of a cylindrical specimen.