Enzymatic Micromotors as a Mobile Photosensitizer Platform for Highly Efficient On‐Chip Targeted Antibacteria Photodynamic Therapy

Photodynamic therapy (PDT) functions when the light‐excited photosensitizers transfer energy to oxygen molecules (³O₂) to produce cytotoxic singlet oxygen (¹O₂) that can effectively kill cells or bacteria. However, the PDT efficacy is often reduced by the limited availability of ³O₂ surrounding the photosensitizer and extremely short diffusion range of the photoactivated ¹O₂. Herein, an enzymatic micromotor based on hollow mesoporous SiO₂ (mSiO₂) microspheres is constructed as a mobile and highly efficient photosensitizer platform. Carboxylated magnetic nanoparticles are connected with both hollow spheres and 5,10,15,20‐tetrakis(4‐aminophenyl)porphyrin molecules through covalent linkage between amino and carboxylic groups within a one‐step reaction. Due to the intrinsic asymmetry of the mSiO₂ spheres, the micromotors can be propelled by ionic diffusiophoresis induced by the enzymatic decomposition of urea. Via numerical simulation, the self‐propulsion mechanism is clarified and the movement direction is identified. By virtue of active self‐propulsion, the current system can overcome the long‐standing shortcomings of PDT and significantly enhance the PDT efficacy by improving the accessibility of the photosensitizer to ³O₂ and enlarging the diffusing range of ¹O₂. Therefore, by proposing a new solution to the bottleneck problems of PDT, this work provides insightful perspectives to the biomedical application of multifunctional micro/nanomotors.     

Magnetically Modulated Pot‐Like MnFe2O4 Micromotors: Nanoparticle Assembly Fabrication and their Capability for Direct Oil Removal

This work demonstrates a simple‐structured, low‐cost magnetically modulated micromotor of MnFe₂O₄ pot‐like hollow microparticles as well as its facile, versatile, and large‐scale growing‐bubble‐templated nanoparticle (NP) assembly fabrication approach. In this approach, the hydrophobic MnFe₂O₄@oleic acid NPs in an oil droplet of chloroform and hexane assembled into a dense NP shell layer due to the hydrophobic interactions between the NP surfaces. With the encapsulated oil continuously vaporizing into high‐pressured gas bubbles, the dense MnFe₂O₄ NP shell layer then bursts, forming an asymmetric pot‐like MnFe₂O₄ micromotor by creating a single hole in it. For the as‐developed simple pot‐like MnFe₂O₄ micromotor, the catalytically generated O₂ molecules nucleate and grow into bubbles preferentially on the inner concave surface rather than on the outer convex surface, resulting in continuous ejection of O₂ bubbles from the open hole to propel it. Dexterously integrating the high catalytic activity for H₂O₂ decomposition to produce O₂ bubbles, excellent magnetic property with the instinctive surface hydrophobicity, the MnFe₂O₄ pot‐like micromotor not only can autonomously move in water media with both velocity and direction modulated by external magnetic field but also can directly serve for environmental oil removal without any further surface modification. The results here may inspire novel practical micromotors.     

Fine‐Motion Estimation Using Ego/Exo‐Cameras

Robust motion estimation for human–computer interactions played an important role in a novel method of interaction with electronic devices. Existing pose estimation using a monocular camera employs either ego‐motion or exo‐motion, both of which are not sufficiently accurate for estimating fine motion due to the motion ambiguity of rotation and translation. This paper presents a hybrid vision‐based pose estimation method for fine‐motion estimation that is specifically capable of extracting human body motion accurately. The method uses an ego‐camera attached to a point of interest and exo‐cameras located in the immediate surroundings of the point of interest. The exo‐cameras can easily track the exact position of the point of interest by triangulation. Once the position is given, the ego‐camera can accurately obtain the point of interest's orientation. In this way, any ambiguity between rotation and translation is eliminated and the exact motion of a target point (that is, ego‐camera) can then be obtained. The proposed method is expected to provide a practical solution for robustly estimating fine motion in a non‐contact manner, such as in interactive games that are designed for special purposes (for example, remote rehabilitation care systems).     

Tailoring Metal/TiO2 Interface to Influence Motion of Light‐Activated Janus Micromotors

Catalytic light‐powered micromotors have become a major focus in current autonomous self‐propelled micromotors research. The attractiveness of such machines stems from the fact that these motors are “fuel‐free,” with their motion modulated by light irradiation. In order to study how different metals affect the velocities of metal/TiO₂ micromachines in the presence of UV irradiation in pure water, Pt/TiO₂, Cu/TiO₂, Fe/TiO₂, Ag/TiO₂, and Au/TiO₂ Janus micromotors are prepared. The metals have different chemical potentials and catalytic effects toward water splitting reaction, with both the effects expected to alter the photoelectrochemically‐induced reaction and propulsion rates. Analysis of structures, elemental compositions, motion patterns, velocities, and overall performances of different metals (Pt, Au, Ag, Fe, Cu) on TiO₂ are observed by scanning electron microscopy, energy dispersive X‐ray spectroscopy, and optical microscopy. Electrochemical Tafel analysis is performed for the different metal/TiO₂ structures and it is concluded that the effective velocity is a result of the synergistic effect of chemical potential and catalysis. It is found that the Pt/TiO₂ Janus micromotors exhibit the fastest motion compared to the rest of the prepared materials. Furthermore, after exposure to UV light, every fabricated micromotor shows high possibility of forming assembled chains which influence their velocity.     

Superassembled Biocatalytic Porous Framework Micromotors with Reversible and Sensitive pH‐Speed Regulation at Ultralow Physiological H2O2 Concentration

Synthetic nano/micromotors are a burgeoning class of materials with vast promise for applications ranging from environmental remediation to nanomedicine. The motility of these motors is generally controlled by the concentration of accessible fuel, and therefore, engineering speed‐regulation mechanisms, particularly using biological triggers, remains a continuing challenge. Here, control over the movement of superassembled porous framework micromotors via a reversible, biological‐relevant pH‐responsive regulatory mechanism is demonstrated. Succinylated β‐lactoglobulin and catalase are superassembled in porous framework particles, where the β‐lactoglobulin is permeable at neutral pH. This permeability allows the fuel (H₂O₂) to access catalase, leading to autonomous movement of the micromotors. However, at mild acidic pH, succinylated β‐lactoglobulin undergoes a reversible gelation process, preventing the access of fuel into the micromotors where the catalase resides. To one's knowledge, this study represents the first example of chemically driven motors with rapid, reversible pH‐responsive motility. Furthermore, the porous framework significantly enhances the biocatalytic activity of catalase, allowing ultralow H₂O₂ concentrations to be exploited at physiological conditions. It is envisioned that the simultaneous exploitation of pH and chemical potential of such nanosystems could have potential applications as stimulus‐responsive drug delivery vehicles that benefit from the complex biological environment.     

Multifunctional Silver‐Exchanged Zeolite Micromotors for Catalytic Detoxification of Chemical and Biological Threats

Multifunctional reactive‐zeolite‐based micromotors have been developed and characterized toward effective and rapid elimination of chemical and biological threats. The incorporation of silver ions (Ag⁺) into aluminosilicate zeolite framework imparts several attractive functions, including strong binding to chemical warfare agents (CWA) followed by effective degradation, and enhanced antibacterial activity. The new zeolite‐micromotors protocol thus combines the remarkable adsorption capacity of zeolites and the efficient catalytic properties of the reactive Ag⁺ ions with the autonomous movement of the zeolite micromotors for an accelerated detoxification of CWA. Furthermore, the high antibacterial activity of Ag⁺ along with the rapid micromotor movement enhances the contact between bacteria and reactive Ag⁺, leading to a powerful “on‐the‐fly” bacteria killing capacity. These attractive adsorptive/catalytic features of the self‐propelled zeolite micromotors eliminate secondary environmental contamination compared to adsorptive micromotors. The distinct cubic geometry of the zeolite micromotors leads to enhanced bubble generation and faster movement, in unique movement trajectories, which increases the fluid convection and highly efficient detoxification of CWA and killing of bacteria. The attractive capabilities of these zeolite micromotors will pave the way for their diverse applications in defense, environmental and biomedical applications in more economical and sustainable manner.     

Real‐Time IR Tracking of Single Reflective Micromotors through Scattering Tissues

Medical micromotors have the potential to lead to a paradigm shift in future biomedicine, as they may perform active drug delivery, microsurgery, tissue engineering, or assisted fertilization in a minimally invasive manner. However, the translation to clinical treatment is challenging, as many applications of single or few micromotors require real‐time tracking and control at high spatiotemporal resolution in deep tissue. Although optical techniques are a popular choice for this task, absorption and strong light scattering lead to a pronounced decrease of the signal‐to‐noise ratio with increasing penetration depth. Here, a highly reflective micromotor is introduced which reflects more than tenfold the light intensity of simple gold particles and can be precisely navigated by external magnetic fields. A customized optical IR imaging setup and an image correlation technique are implemented to track single micromotors in real‐time and label‐free underneath phantom and ex vivo mouse skull tissues. As a potential application, the micromotors speed is recorded when moving through different viscous fluids to determine the viscosity of diverse physiological fluids toward remote cardiovascular disease diagnosis. Moreover, the micromotors are loaded with a model drug to demonstrate their cargo‐transport capability. The proposed reflective micromotor is suitable as theranostic tool for sub‐skin or organ‐on‐a‐chip applications.     

Catalytic and Light‐Driven ZnO/Pt Janus Nano/Micromotors: Switching of Motion Mechanism via Interface Roughness and Defect Tailoring at the Nanoscale

The first models of mesoporous ZnO/Pt Janus micromotors that show fuel‐free and light‐powered propulsion depending on the interface roughness are shown. Two models of ZnO semiconducting particles with distinct surface morphologies and pore structures are synthesized by self‐aggregation of primary nanoparticles and nanosheets into nanoscale rough and smooth microparticles, respectively. The self‐assembled nanosheet model (smooth) provides a large surface for the formation of a continuous Pt layer with strong adherence, whereas the discontinuous Pt species take place inside the inter‐nanoparticles pores in the self‐assembled nanoparticle model (rough). The effects of the interface, surface porosity, defect, and charge transfer on the light‐powered motion for both well‐designed mesoporous ZnO/Pt Janus micromotors are investigated and compared to find the underlying propulsion mechanisms. The degradation of two model pollutants is demonstrated as a proof‐of‐concept application of these carefully engineered Janus micromotors. In this work, it is shown that by discreet material fabrication together with semiconductor/metal interface charge transport interpretation, it would be possible to develop new light‐driven Janus micromotors based on other photocatalysts containing active surfaces such as TiO₂.     

Aqueous Two‐Phase System Patterning of Microbubbles: Localized Induction of Apoptosis in Sonoporated Cells

Ultrasound‐driven microbubbles produce mechanical forces that can disrupt cell membranes (sonoporation). However, it is difficult to control microbubble location with respect to cells. This lack of control leads to low sonoporation efficiencies and variable outcomes. In this study, aqueous two‐phase system (ATPS) droplets are used to localize microbubbles in select micro‐regions at the surface of living cells. This is achieved by stably partitioning microbubbles in dextran (DEX) droplets, deposited on living adherent cells in medium containing polyethylene glycol (PEG). The interfacial energy at the PEG‐DEX interface overcomes microbubble buoyancy and prevents microbubbles from floating away from the cells. Spreading of the small DEX droplets retains microbubbles at the cell surface in defined lateral positions without the need for antibody or cell‐binding ligand conjugation. The patterned microbubbles are activated on a cell monolayer exposed to a broadly applied ultrasound field (center frequency 1.25 MHz, active element diameter 0.6 cm, pulse duration 8 μs or 30 s). This system enables efficient testing of different ultrasound conditions for their effects on sonoporation‐mediated membrane disruption and cell viability. Regions of cells without patterned microbubbles show no injury or membrane disruption. In microbubble patterned regions, 8 μs ultrasound pulses (0.2‐0.6 MPa) produce cell death that is primarily apoptotic. Ultrasound‐induced apoptosis increases with higher extracellular calcium concentrations, with cells displaying all of the hallmarks of apoptosis including annexinV labeling, loss of mitochondrial membrane potential, caspase activation and changes in nuclear morphology.     

Rapid Self‐Assembly of Macroscale Tissue Constructs at Biphasic Aqueous Interfaces

An entirely new approach to tissue engineering is presented that uses the interfacial forces between aqueous solutions of phase‐separating polymers to confine cells and promote their assembly into interconnected, macroscopic tissue constructs. This simple and inexpensive general procedure creates free‐standing, centimeter‐scale constructs from cell suspensions at the interface between poly(ethylene glycol) and dextran aqueous two‐phase systems in as little as 2 h. Using this method, skin constructs are produced that integrate with decellularized dermal matrices, on which they differentiate and stratify into skin equivalents. It is demonstrated that the constructs produced by this method have appropriate integrity and mechanical properties for use as in vitro tissue models.     

Programmable Functionalization of Surfactant‐Stabilized Microfluidic Droplets via DNA‐Tags

Droplet‐based microfluidics has emerged as a powerful tool in synthetic biology. For many applications, chemical functionalization of the droplets is a key process. Therefore, a straightforward and broadly applicable approach is developed to functionalize the inner periphery of microfluidic droplets with diverse reactive groups and components. Instead of covalent modification of the droplet‐stabilizing surfactants, this method relies on cholesterol‐tagged DNA that self‐assembles at the droplet periphery. The cholesterol‐tagged DNA serves as an attachment handle for the recruitment of complementary DNA. The complementary DNA can carry diverse functional groups. We exemplify our method by demonstrating the attachment of amine groups, DNA nanostructures, microspheres, a minimal actin cortex, and leukemia cells to the droplet periphery. It is further shown that the DNA‐mediated attachment to the droplet periphery is temperature‐responsive and reversible. It is envisioned that droplet functionalization via DNA handles will help to tailor droplet interfaces for diverse applications—featuring programmable assembly, unique addressability, and stimuli‐responsiveness.     

An Autonomous Soft Actuator with Light‐Driven Self‐Sustained Wavelike Oscillation for Phototactic Self‐Locomotion and Power Generation

Mimicking the intelligence of biological organisms in artificial systems to design smart actuators that act autonomously in response to constant environmental stimuli is crucial to the construction of intelligent biomimetic robots and devices, but remains a great challenge. Here, a light‐driven autonomous carbon‐nanotube‐based bimorph actuator is developed through an elaborate structural design. This curled droplet‐shaped actuator can be simply driven by constant white light irradiation, self‐propelled by a light‐mechanical negative feedback loop created by light‐driven actuation, time delay in the photothermal response along the actuator, and good elasticity from the curled structure, performing a continuously self‐oscillating motion in a wavelike fashion, which mimics the human sit‐up motion. Moreover, this autonomous self‐oscillating motion can be further tuned by controlling the intensity and direction of the incident light. The autonomous actuator with continuous wavelike oscillating motion shows immense potential in light‐driven biomimetic soft robots and optical‐energy‐harvesting devices. Furthermore, a self‐locomotive artificial snake with phototaxis is constructed, which autonomously and continuously crawls toward the light source in a wave‐propagating manner under constant light irradiation. This snake can be placed on a substrate made of triboelectric materials to realize continuous electric output when exposed to constant light illumination.     

High Throughput,Polymeric Aqueous Two‐Phase Printing of Tumor Spheroids

This paper presents a new 3D culture microtechnology for high throughput production of tumor spheroids and validates its utility for screening anti‐cancer drugs. Two immiscible polymeric aqueous solutions are used and a submicroliter drop of the “patterning” phase containing cells is microprinted into a bath of the “immersion” phase. Selecting proper formulations of biphasic systems using a panel of biocompatible polymers results in the formation of a round drop that confines cells to facilitate spontaneous formation of a spheroid without any external stimuli. Adapting this approach to robotic tools enables straightforward generation and maintenance of spheroids of well‐defined size in standard microwell plates and biochemical analysis of spheroids in situ, which is not possible with existing techniques for spheroid culture. To enable high throughput screening, a phase diagram is established to identify minimum cell densities within specific volumes of the patterning drop to result in a single spheroid. Spheroids show normal growth over long‐term incubation and dose‐dependent decrease in cellular viability when treated with drug compounds, but present significant resistance compared to monolayer cultures. The unprecedented ease of implementing this microtechnology and its robust performance will benefit high throughput studies of drug screening against cancer cells with physiologically relevant 3D tumor models.     

Microfluidic Fabrication of Capsule Sensor Platform with Double‐Shell Structure

Metal nanoparticles are frequently employed for the colorimetric detection of specific target molecules using an aggregation‐induced shift of the localized surface plasmon resonance. However, metal nanoparticles dispersed in bulk solutions are prone to be contaminated by adhesive molecules and the dispersions tend to be diluted by sample fluids, restricting direct application to unpurified pristine samples. Here, a versatile capsule sensor platform is proposed that can encompass a variety of different types of nanoparticle‐based sensors. The capsule sensors are microfluidically prepared to obtain close control over their dimensions and composition. Their aqueous cores that are loaded with sensing materials are surrounded by an ultrathin inner oil shell and an outer hydrogel shell. The hydrogel shell prevents the diffusion of large adhesive molecules into the core, thereby preventing contamination of the sensing materials. The oil shell is selectively permeable such that it further improves the sensor selectivity. Importantly, these shells confine the sensing materials and prevent them from being diluted, securing a consistent optical property. Moreover, the capsule‐based sensors display a higher sensitivity than bulk dispersions because a smaller amount of sensing materials is used. The power of nanoparticle‐loaded capsule sensors is demonstrated using lysine‐coated gold nanoparticles to detect mercury ions.     

Fine‐Tuning of Yellow or Red Photo‐ and Electroluminescence of Functional Difluoro‐boradiazaindacene Films

The present work describes the synthesis of difluoro‐boradiazaindacenes (Bodipy) functionalized at the central 8‐position by phenylamino moieties easily transformable into phenyl amide scaffoldings. Molecules carrying three linear or branched chains were prepared and characterized. An X‐ray crystal structure for the pivotal trimethoxyphenyl‐Bodipy derivative was determined, and the packing is discussed in terms of molecular interactions; a key feature for the formation of thin films. All of the dyes are thermally stable up to 170 °C but no liquid‐crystalline phases are observed. Reversible reduction and oxidation processes occur around +0.97 and −1.34 V, respectively, versus saturated calomel electrode in solution and the electroactivity and photoluminescence are maintained in thin films produced by vacuum evaporation. Interestingly, two distinct emissions are observed at 550 and 635 nm by electroluminescence of the trimethoxyphenyl‐Bodipy derivative, corresponding to the luminescence of isolated molecules and dimers, respectively. Doping Alq₃ films with this Bodipy molecule by vacuum evaporation produces organic light‐emitting diodes (OLEDs) in which very efficient energy transfer from the Alq₃ matrix to the Bodipy occurs by a resonance mechanism involving the first Bodipy excited state. Yellow light (550 nm, 344 cd m⁻² at 15 V) is emitted at low doping concentration (7 mol %), whereas red light (635 nm, 125 cd m⁻² at 15 V) is emitted at higher concentration (19 mol %). Dispersion of the Bodipy into a fluorescent poly(N‐vinylcarbazole) polymer (PVK) (≈3 mol % per repeating unit of PVK) by solution processing exclusively produces yellow emission owing to the isolated Bodipyfluorophore (550 nm, 213 cd m⁻² at 15 V). The second excited state of the Bodipy dye is likely involved during energy transfer from the PVK matrix.