A Naturally Inspired Extrusion-Based Microfluidic Approach for Manufacturing Tailorable Magnetic Soft Continuum Microrobotic Devices.

Soft materials play a crucial role in small-scale robotic applications by closely mimicking the complex motion and morphing behavior of organisms. However, conventional fabrication methods face challenges in creating highly integrated small-scale soft devices. In this study, microfluidics is leveraged to precisely control reaction-diffusion (RD) processes to generate multifunctional and compartmentalized calcium-cross-linkable alginate-based microfibers. Under RD conditions, sophisticated alginate-based fibers are produced for magnetic soft continuum robotics applications with customizable features, such as geometry (compact or hollow), degree of cross-linking, and the precise localization of magnetic nanoparticles (inside the core, surrounding the fiber, or on one side). This fine control allows for tuning the stiffness and magnetic responsiveness of the microfibers. Additionally, chemically cleavable regions within the fibers enable disassembly into smaller robotic units or roll-up structures under a rotating magnetic field. These findings demonstrate the versatility of microfluidics in processing highly integrated small-scale devices.

Research on the Vision-Based Dairy Cow Ear Tag Recognition Method.

With the increase in the scale of breeding at modern pastures, the management of dairy cows has become much more challenging, and individual recognition is the key to the implementation of precision farming. Based on the need for low-cost and accurate herd management and for non-stressful and non-invasive individual recognition, we propose a vision-based automatic recognition method for dairy cow ear tags. Firstly, for the detection of cow ear tags, the lightweight Small-YOLOV5s is proposed, and then a differentiable binarization network (DBNet) combined with a convolutional recurrent neural network (CRNN) is used to achieve the recognition of the numbers on ear tags. The experimental results demonstrated notable improvements: Compared to those of YOLOV5s, Small-YOLOV5s enhanced recall by 1.5%, increased the mean average precision by 0.9%, reduced the number of model parameters by 5,447,802, and enhanced the average prediction speed for a single image by 0.5 ms. The final accuracy of the ear tag number recognition was an impressive 92.1%. Moreover, this study introduces two standardized experimental datasets specifically designed for the ear tag detection and recognition of dairy cows. These datasets will be made freely available to researchers in the global dairy cattle community with the intention of fostering intelligent advancements in the breeding industry.

Multilevel design and construction in nanomembrane rolling for three-dimensional angle-sensitive photodetection.

Releasing pre-strained two-dimensional nanomembranes to assemble on-chip three-dimensional devices is crucial for upcoming advanced electronic and optoelectronic applications. However, the release process is affected by many unclear factors, hindering the transition from laboratory to industrial applications. Here, we propose a quasistatic multilevel finite element modeling to assemble three-dimensional structures from two-dimensional nanomembranes and offer verification results by various bilayer nanomembranes. Take Si/Cr nanomembrane as an example, we confirm that the three-dimensional structural formation is governed by both the minimum energy state and the geometric constraints imposed by the edges of the sacrificial layer. Large-scale, high-yield fabrication of three-dimensional structures is achieved, and two distinct three-dimensional structures are assembled from the same precursor. Six types of three-dimensional Si/Cr photodetectors are then prepared to resolve the incident angle of light with a deep neural network model, opening up possibilities for the design and manufacturing methods of More-than-Moore-era devices.

Clustering analysis for the evolutionary relationships of SARS-CoV-2 strains.

To explore the differences and relationships between the available SARS-CoV-2 strains and predict the potential evolutionary direction of these strains, we employ the hierarchical clustering analysis to investigate the evolutionary relationships between the SARS-CoV-2 strains utilizing the genomic sequences collected in China till January 7, 2023. We encode the sequences of the existing SARS-CoV-2 strains into numerical data through k-mer algorithm, then propose four methods to select the representative sample from each type of strains to comprise the dataset for clustering analysis. Three hierarchical clustering algorithms named Ward-Euclidean, Ward-Jaccard, and Average-Euclidean are introduced through combing the Euclidean and Jaccard distance with the Ward and Average linkage clustering algorithms embedded in the OriginPro software. Experimental results reveal that BF.28, BE.1.1.1, BA.5.3, and BA.5.6.4 strains exhibit distinct characteristics which are not observed in other types of SARS-CoV-2 strains, suggesting their being the majority potential sources which the future SARS-CoV-2 strains' evolution from. Moreover, BA.2.75, CH.1.1, BA.2, BA.5.1.3, BF.7, and B.1.1.214 strains demonstrate enhanced abilities in terms of immune evasion, transmissibility, and pathogenicity. Hence, closely monitoring the evolutionary trends of these strains is crucial to mitigate their impact on public health and society as far as possible.

3D Motion Manipulation for Micro- and Nanomachines: Progress and Future Directions.

In the past decade, micro- and nanomachines (MNMs) have made outstanding achievements in the fields of targeted drug delivery, tumor therapy, microsurgery, biological detection, and environmental monitoring and remediation. Researchers have made significant efforts to accelerate the rapid development of MNMs capable of moving through fluids by means of different energy sources (chemical reactions, ultrasound, light, electricity, magnetism, heat, or their combinations). However, the motion of MNMs is primarily investigated in confined two-dimensional (2D) horizontal setups. Furthermore, three-dimensional (3D) motion control remains challenging, especially for vertical movement and control, significantly limiting its potential applications in cargo transportation, environmental remediation, and biotherapy. Hence, an urgent need is to develop MNMs that can overcome self-gravity and controllably move in 3D spaces. This review delves into the latest progress made in MNMs with 3D motion capabilities under different manipulation approaches, discusses the underlying motion mechanisms, explores potential design concepts inspired by nature for controllable 3D motion in MNMs, and presents the available 3D observation and tracking systems.

"On-The-Fly" Synthesis of Self-Supported LDH Hollow Structures Through Controlled Microfluidic Reaction-Diffusion Conditions.

Layered double hydroxides (LDHs) are a class of functional materials that exhibit exceptional properties for diverse applications in areas such as heterogeneous catalysis, energy storage and conversion, and bio-medical applications, among others. Efforts have been devoted to produce millimeter-scale LDH structures for direct integration into functional devices. However, the controlled synthesis of self-supported continuous LDH materials with hierarchical structuring up to the millimeter scale through a straightforward one-pot reaction method remains unaddressed. Herein, it is shown that millimeter-scale self-supported LDH structures can be produced by means of a continuous flow microfluidic device in a rapid and reproducible one-pot process. Additionally, the microfluidic approach not only allows for an "on-the-fly" formation of unprecedented LDH composite structures, but also for the seamless integration of millimeter-scale LDH structures into functional devices. This method holds the potential to unlock the integrability of these materials, maintaining their performance and functionality, while diverging from conventional techniques like pelletization and densification that often compromise these aspects. This strategy will enable exciting advancements in LDH performance and functionality.

On-Command Disassembly of Microrobotic Superstructures for Transport and Delivery of Magnetic Micromachines.

Magnetic microrobots have been developed for navigating microscale environments by means of remote magnetic fields. However, limited propulsion speeds at small scales remain an issue in the maneuverability of these devices as magnetic force and torque are proportional to their magnetic volume. Here, a microrobotic superstructure is proposed, which, as analogous to a supramolecular system, consists of two or more microrobotic units that are interconnected and organized through a physical (transient) component (a polymeric frame or a thread). The superstructures consist of microfabricated magnetic helical micromachines interlocked by a magnetic gelatin nanocomposite containing iron oxide nanoparticles (IONPs). While the microhelices enable the motion of the superstructure, the IONPs serve as heating transducers for dissolving the gelatin chassis via magnetic hyperthermia. In a practical demonstration, the superstructure's motion with a gradient magnetic field in a large channel, the disassembly of the superstructure and release of the helical micromachines by a high-frequency alternating magnetic field, and the corkscrew locomotion of the released helices through a small channel via a rotating magnetic field, is showcased. This adaptable microrobotic superstructure reacts to different magnetic inputs, which can be used to perform complex delivery procedures within intricate regions of the human body.

Tailored Design of a Water-Based Nanoreactor Technology for Producing Processable Sub-40 Nm 3D COF Nanoparticles at Atmospheric Conditions.

Covalent organic frameworks (COFs) are crystalline materials with intrinsic porosity that offer a wide range of potential applications spanning diverse fields. Yet, the main goal in the COF research area is to achieve the most stable thermodynamic product while simultaneously targeting the desired size and structure crucial for enabling specific functions. While significant progress is made in the synthesis and processing of 2D COFs, the development of processable 3D COF nanocrystals remains challenging. Here, a water-based nanoreactor technology for producing processable sub-40 nm 3D COF nanoparticles at ambient conditions is presented. Significantly, this technology not only improves the processability of the synthesized 3D COF, but also unveils exciting possibilities for their utilization in previously unexplored domains, such as nano/microrobotics and biomedicine, which are limited by larger crystallites.

Recent Developments in Metallic Degradable Micromotors for Biomedical and Environmental Remediation Applications.

Synthetic micromotor has gained substantial attention in biomedicine and environmental remediation. Metal-based degradable micromotor composed of magnesium (Mg), zinc (Zn), and iron (Fe) have promise due to their nontoxic fuel-free propulsion, favorable biocompatibility, and safe excretion of degradation products Recent advances in degradable metallic micromotor have shown their fast movement in complex biological media, efficient cargo delivery and favorable biocompatibility. A noteworthy number of degradable metal-based micromotors employ bubble propulsion, utilizing water as fuel to generate hydrogen bubbles. This novel feature has projected degradable metallic micromotors for active in vivo drug delivery applications. In addition, understanding the degradation mechanism of these micromotors is also a key parameter for their design and performance. Its propulsion efficiency and life span govern the overall performance of a degradable metallic micromotor. Here we review the design and recent advancements of metallic degradable micromotors. Furthermore, we describe the controlled degradation, efficient in vivo drug delivery, and built-in acid neutralization capabilities of degradable micromotors with versatile biomedical applications. Moreover, we discuss micromotors' efficacy in detecting and destroying environmental pollutants. Finally, we address the limitations and future research directions of degradable metallic micromotors.

Magnetic PiezoBOTs: a microrobotic approach for targeted amyloid protein dissociation.

Piezoelectric nanomaterials have become increasingly popular in the field of biomedical applications due to their high biocompatibility and ultrasound-mediated piezocatalytic properties. In addition, the ability of these nanomaterials to disaggregate amyloid proteins, which are responsible for a range of diseases resulting from the accumulation of these proteins in body tissues and organs, has recently gained considerable attention. However, the use of nanoparticles in biomedicine poses significant challenges, including targeting and uncontrolled aggregation. To address these limitations, our study proposes to load these functional nanomaterials on a multifunctional mobile microrobot (PiezoBOT). This microrobot is designed by coating magnetic and piezoelectric barium titanate nanoparticles on helical biotemplates, allowing for the combination of magnetic navigation and ultrasound-mediated piezoelectric effects to target amyloid disaggregation. Our findings demonstrate that acoustically actuated PiezoBOTs can effectively reduce the size of aggregated amyloid proteins by over 80% in less than 10 minutes by shortening and dissociating constituent amyloid fibrils. Moreover, the PiezoBOTs can be easily magnetically manipulated to actuate the piezocatalytic nanoparticles to specific amyloidosis-affected tissues or organs, minimizing side effects. These biocompatible PiezoBOTs offer a promising non-invasive therapeutic approach for amyloidosis diseases by targeting and breaking down protein aggregates at specific organ or tissue sites.

In Situ Sprayed Nanovaccine Suppressing Exosomal PD-L1 by Golgi Apparatus Disorganization for Postsurgical Melanoma Immunotherapy.

The anti-PD-L1 immunotherapy has shown promise in treating cancer. However, certain patients with metastatic cancer have low response and high relapse rates. A main reason is systemic immunosuppression caused by exosomal PD-L1, which can circulate in the body and inhibit T cell functions. Here, we show that Golgi apparatus-Pd-l1-/- exosome hybrid membrane coated nanoparticles (GENPs) can significantly reduce the secretion of PD-L1. The GENPs can accumulate in tumors through homotypic targeting and effectively deliver retinoic acid, inducing disorganization of the Golgi apparatus and a sequence of intracellular events including alteration of endoplasmic reticulum (ER)-to-Golgi trafficking and subsequent ER stress, which finally disrupts the PD-L1 production and the release of exosomes. Furthermore, GENPs could mimic exosomes to access draining lymph nodes. The membrane antigen of PD-l1-/- exosome on GENPs can activate T cells through a vaccine-like effect, strongly promoting systemic immune responses. By combining GENPs with anti-PD-L1 treatment in the sprayable in situ hydrogel, we have successfully realized a low recurrence rate and substantially extended survival periods in mice models with incomplete metastatic melanoma resection.

The magnetopyroelectric effect: heat-mediated magnetoelectricity in magnetic nanoparticle-ferroelectric polymer composites.

Magnetoelectricity enables a solid-state material to generate electricity under magnetic fields. Most magnetoelectric composites are developed through a strain-mediated route by coupling piezoelectric and magnetostrictive phases. However, the limited availability of high-performance magnetostrictive components has become a constraint for the development of novel magnetoelectric materials. Here, we demonstrate that nanostructured composites of magnetic and pyroelectric materials can generate electrical output, a phenomenon we refer to as the magnetopyroelectric (MPE) effect, which is analogous to the magnetoelectric effect in strain-mediated composite multiferroics. Our composite consists of magnetic iron oxide nanoparticles (IONPs) dispersed in a ferroelectric (and also pyroelectric) poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) matrix. Under a high-frequency low-magnitude alternating magnetic field, the IONPs generate heat through hysteresis loss, which stimulates the depolarization process of the pyroelectric polymer. This magnetopyroelectric approach creates a new opportunity to develop magnetoelectric materials for a wide range of applications.

Filler-Enhanced Piezoelectricity of Poly-L-Lactide and Its Use as a Functional Ultrasound-Activated Biomaterial.

Poly-L-lactide (PLLA) offers a unique possibility for processing into biocompatible, biodegradable, and implantable piezoelectric structures. With such properties, PLLA has potential to be used as an advanced tool for mimicking biophysical processes that naturally occur during the self-repair of wounds and damaged tissues, including electrostimulated regeneration. The piezoelectricity of PLLA strongly depends on the possibility of controlling its crystallinity and molecular orientation. Here, it is shown that modifying PLLA with a small amount (1 wt%) of crystalline filler particles with a high aspect ratio, which act as nucleating agents during drawing-induced crystallization, promotes the formation of highly crystalline and oriented PLLA structures. This increases their piezoelectricity, and the filler-modified PLLA films provide a 20-fold larger voltage output than nonmodified PLLA during ultrasound (US)-assisted activation. With 99% PLLA content, the ability of the films to produce reactive oxygen species (ROS) and increase the local temperature during interactions with US is shown to be very low. US-assisted piezostimulation of adherent cells directly attach to their surface (such as skin keratinocytes), stimulate cytoskeleton formation, and as a result cells elongate and orient themselves in a specific direction that align with the direction of PLLA film drawing and PLLA dipole orientation.

Shape-memory effect in twisted ferroic nanocomposites.

The shape recovery ability of shape-memory alloys vanishes below a critical size (~50 nm), which prevents their practical applications at the nanoscale. In contrast, ferroic materials, even when scaled down to dimensions of a few nanometers, exhibit actuation strain through domain switching, though the generated strain is modest (~1%). Here, we develop freestanding twisted architectures of nanoscale ferroic oxides showing shape-memory effect with a giant recoverable strain (>8%). The twisted geometrical design amplifies the strain generated during ferroelectric domain switching, which cannot be achieved in bulk ceramics or substrate-bonded thin films. The twisted ferroic nanocomposites allow us to overcome the size limitations in traditional shape-memory alloys and open new avenues in engineering large-stroke shape-memory materials for small-scale actuating devices such as nanorobots and artificial muscle fibrils.

Multi-target cell therapy using a magnetoelectric microscale biorobot for targeted delivery and selective differentiation of SH-SY5Y cells via magnetically driven cell stamping.

Cell therapy refers to a treatment that involves the delivery of cells or cellular material by means of injection, grafting, or implantation in order to replace damaged tissue and restore its function, or to aid the body in fighting disease. However, limitations include poor targeting delivery and low therapeutic efficacy due to low cell survival. Hence, novel approaches are required to increase cell delivery efficiency and enhance therapeutic efficacy via selective cell differentiation at target areas. Here, we present a stamping magnetoelectric microscale biorobot (SMMB) consisting of neuron-like cell spheroids loaded with magnetoelectric nanoparticles. The SMMB enables not only effective targeted delivery of cells to multiple target areas (via minimally invasive stamping employing magnetic actuation) but also facilitates selective neuronal differentiation via magnetoelectric (ME) stimulation. This ensures rapid colonization and enhances efficacy. SMMBs were fabricated using SH-SY5Y cells. Magnetoelectric nanoparticles for ME stimulation responded to an alternating magnetic field that ensured targeted cell differentiation. Multi-target cell therapy facilitated the targeted delivery and selective differentiation of SH-SY5Y cells to multiple regions using a single SMMB with rotating and alternating magnetic fields for delivery and ME stimulation. This promising tool may overcome the limitations of existing cell therapy for neurodegenerative diseases.

MoSBOTs: Magnetically Driven Biotemplated MoS2 -Based Microrobots for Biomedical Applications.

2D layered molybdenum disulfide (MoS2 ) nanomaterials are a promising platform for biomedical applications, particularly due to its high biocompatibility characteristics, mechanical and electrical properties, and flexible functionalization. Additionally, the bandgap of MoS2 can be engineered to absorb light over a wide range of wavelengths, which can then be transformed into local heat for applications in photothermal tissue ablation and regeneration. However, limitations such as poor stability of aqueous dispersions and low accumulation in affected tissues impair the full realization of MoS2 for biomedical applications. To overcome such challenges, herein, multifunctional MoS2 -based magnetic helical microrobots (MoSBOTs) using cyanobacterium Spirulina platensis are proposed as biotemplate for therapeutic and biorecognition applications. The cytocompatible microrobots combine remote magnetic navigation with MoS2 photothermal activity under near-infrared irradiation. The resulting photoabsorbent features of the MoSBOTs are exploited for targeted photothermal ablation of cancer cells and on-the-fly biorecognition in minimally invasive oncotherapy applications. The proposed multi-therapeutic MoSBOTs hold considerable potential for a myriad of cancer treatment and diagnostic-related applications, circumventing current challenges of ablative procedures.

Magnetoelectric Effect in Hydrogen Harvesting: Magnetic Field as a Trigger of Catalytic Reactions.

Magnetic fields have been regarded as an additional stimulus for electro- and photocatalytic reactions, but not as a direct trigger for catalytic processes. Multiferroic/magnetoelectric materials, whose electrical polarization and surface charges can be magnetically altered, are especially suitable for triggering and control of catalytic reactions solely with magnetic fields. Here, it is demonstrated that magnetic fields can be employed as an independent input energy source for hydrogen harvesting by means of the magnetoelectric effect. Composite multiferroic CoFe2 O4 -BiFeO3 core-shell nanoparticles act as catalysts for the hydrogen evolution reaction (HER), which is triggered when an alternating magnetic field is applied to an aqueous dispersion of the magnetoelectric nanocatalysts. Based on density functional calculations, it is proposed that the hydrogen evolution is driven by changes in the ferroelectric polarization direction of BiFeO3 caused by the magnetoelectric coupling. It is believed that the findings will open new avenues toward magnetically induced renewable energy harvesting.

Inhibition of tumor recurrence and metastasis via a surgical tumor-derived personalized hydrogel vaccine.

Tumor recurrence and metastasis have become thorny problems in clinical tumor therapy. Vaccine-mediated antitumor immune response has emerged as a significant postoperative inhibition for tumor recurrence and metastasis. However, limited tumor antigens are not conducive to trigger complete antigen-specific T cell-mediated immune responses. Herein, the design of a hydrogel vaccine system containing a granulocyte-macrophage colony stimulating factor (GM-CSF), based on surgically removed tumor cell lysates, was reported. The hydrogel was formed by crosslinking tumor cell lysates and alginate at low temperatures. The GM-CSF was released from the hydrogel to recruit dendritic cells (DCs), which provided a completely personalized tumor antigen pool. They were combined to foster the production of powerful antigen-specific T cells. The personalized hydrogel was implanted at the surgical site and it stimulated the antitumor immune response for the inhibition of residual tumor cells. Delightfully, the personalized hydrogel inhibited the tumor recurrence and metastasis well in a post-surgical mice tumor model, in combination with a programmed death-ligand 1 antibody (αPD-L1). The results demonstrated that the development of a personalized hydrogel and a combination of αPD-L1 provided a new strategy to prevent tumor recurrence and metastasis.

Thermoset Shape Memory Polymer Variable Stiffness 4D Robotic Catheters.

Variable stiffness catheters are typically composed of an encapsulated core. The core is usually composed of a low melting point alloy (LMPA) or a thermoplastic polymer (TP). In both cases, there is a need to encapsulate the core with an elastic material. This imposes a limit to the volume of variable stiffness (VS) material and limits miniaturization. This paper proposes a new approach that relies on the use of thermosetting materials. The variable stiffness catheter (VSC) proposed in this work eliminates the necessity for an encapsulation layer and is made of a unique biocompatible thermoset polymer with an embedded heating system. This significantly reduces the final diameter, improves manufacturability, and increases safety in the event of complications. The device can be scaled to sub-millimeter dimensions, while maintaining a high stiffness change. In addition, integration into a magnetic actuation system allows for precise actuation of one or multiple tools.

Biodegradable Small-Scale Swimmers for Biomedical Applications.

Most forms of biomatter are ephemeral, which means they transform or deteriorate after a certain time. From this perspective, implantable healthcare devices designed for temporary treatments should exhibit the ability to degrade and either blend in with healthy tissues, or be cleared from the body with minimal disruption after accomplishing their designated tasks. This topic is currently being investigated in the field of biomedical micro- and nanoswimmers. These tiny devices have the ability to move through fluids by converting physical or chemical energy into motion. Several architectures of these devices have been designed to mimic the motion strategies of nature's motile microorganisms and cells. Due to their motion abilities, these devices have been proposed as minimally invasive tools for precision healthcare applications. Hence, a natural progression in this field is to produce motile structures that can adopt, or even surpass, similar transient features as biological systems. The fate of small-scale swimmers after accomplishing their therapeutic mission is critical for the successful translation of small-scale swimmers' technologies into clinical applications. In this review, recent research efforts are summarized on the topic of biodegradable micro- and nanoswimmers for biomedical applications, with a focus on targeted therapeutic delivery.