Search

Highlights: This review discusses the potential of degradable metallic micromotors for a variety of biomedical and environmental applications. The design principles, fabrication techniques and degradation mechanisms of degradable metallic micromotors are reviewed in detail. Challenges and future directions for the development of degradable metallic micromotors for real-life applications are presented. 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. [ABSTRACT FROM AUTHOR]

The past decade has seen an upsurge in the development of small‐scale magnetic robots for various biomedical applications. However, many of the reported designs comprise components with biocompatibility concerns. Strategies for fabricating biocompatible and degradable microrobots are required. In this study, polyvinyl alcohol (PVA)‐based magnetic hydrogel microrobots with different morphologies and tunable stability are developed by combining a 3D printed template‐assisted casting with a salting‐out process. 3D sacrificial micromolds are prepared via direct laser writing to shape PVA‐magnetic nanoparticle composite hydrogel microrobots with high architectural complexity. By adjusting the PVA composition and salting‐out parameters, the hydrogel dissolubility can be customized. Due to their high mobility, tunable stability, and high biocompatibility, these PVA‐based magnetic microrobots are suitable platforms for targeted drug and cell delivery. [ABSTRACT FROM AUTHOR]

Magnetoelectric (ME) oxide materials can convert magnetic input into electric output and vice versa, making them excellent candidates for advanced sensing, data storage, and communication. However, their application has been limited to rigid devices due to their brittle nature. Here, flexible ME oxide composite (BaTiO3/CoFe2O4) thin film nanostructures with distinct ME coupling coefficients are reported. In contrast to rigid bulk counterparts, these ceramic nanostructures display a flexible behavior after being released from the substrate, and can be transferred onto a stretchable substrate such as polydimethylsiloxane. These ceramic films possess high ME coefficients due to minimized clamping effect and preferred crystalline orientation, and exhibit reversibly tunable ME coupling via mechanical stretching thanks to their large elasticity (>4%). It is believed that the study can open up new avenues for integrating ceramic ME composites into micro‐/nanoelectromechanical system and soft robotic devices. [ABSTRACT FROM AUTHOR]

A vector hydrophone is an underwater acoustic sensor that can detect the direction of a sound source. Wide-band characteristics and high sensitivity enhance the performance of underwater surveillance systems in complex environments. A vector hydrophone comprising a triaxial piezoelectric accelerometer and spherical hydrophone was fabricated and tested in the air and underwater. The vector hydrophone was designed to exceed the quantitative figures of merit (i.e., receiving voltage sensitivity and bandwidth) of commercially available hydrophones. Accelerometer performance was enhanced by placing a pair of piezoelectric single crystals on each axis and modifying the seismic mass material. The receiving voltage sensitivity of the omnidirectional hydrophone was approximately −160 dB relative to 1   V / μ Pa with the amplifier in water; the sensitivity of the accelerometer exceeded 300 mV/g in air and −215 dB relative to 1   V / μ Pa underwater over the frequency range of interest. The receiving directivity of the vector hydrophone was validated underwater, which confirmed that it could detect the direction of a sound source. [ABSTRACT FROM AUTHOR]

This paper presents a novel Adaptive Genetic Algorithm for optimal path planning of multiple nanoparticles during the nanomanipulation process. The proposed approach determines the optimal manipulation path in the presence of surface roughness and environment obstacles by considering constraints imposed on the nanomanipulation process. In this research, first by discretizing the environment, an initial set of feasible paths were generated, and then, path optimization was continued in the original continuous environment (and not in the discrete environment). The presented novel approach for path planning in continuous environment (1) makes the algorithm independent of grid size, which is the main limitation in conventional path planning methods, and (2) creates a curve path, instead of piecewise linear one, which increases the accuracy and smoothness of the path considerably. Every path is evaluated based on three factors: the displacement effort (the area under critical force-time diagram during nanomanipulation), surface roughness along the path, and smoothness of the path. Using the weighted linear sum of the mentioned three factors as the objective function provides the opportunity to (1) find a path with optimal value for all factors, (2) increase/decrease the effect of a factor based on process considerations. While the former can be obtained by a simple weight tuning procedure introduced in this paper, the latter can be obtained by increasing/decreasing the weight value associated with a factor. In the case of multiple nanoparticles, a co-evolutionary adaptive algorithm is introduced to find the best destination for each nanoparticle, the best sequence of movement, and optimal path for each nanoparticle. By introducing two new operators, it was shown that the performance of the presented co-evolutionary mechanism outperforms the similar previous works. Finally, the proposed approach was also developed based on a modified Particle Swarm Optimization algorithm, and its performance was compared with the proposed Adaptive Genetic Algorithm. [ABSTRACT FROM AUTHOR]

We report that ultra-thin tellurium (Te) nanoflakes were successfully grown on a sample of a gold-coated textile, which then was used as an active piezoelectric material. An output voltage of 4 V and a current of 300 nA were obtained from the bending test under a driving frequency of 10 Hz. To test the practical applications, Te nanoflake nanogenerator (TFNG) device was attached to the subject’s arm, and mechanical energy was converted to electrical energy by means of periodic arm-bending motions. The optimized open-circuit voltage and short-circuit current density of approximately 125 V and 17 μA/cm 2 , respectively, were observed when a TFNG device underwent a compression test with a compressive force of 8 N and driving frequency of 10 Hz. This high-power generation enabled the instantaneous powering of 10 green light-emitting diodes that shone without any assistance from an external power source. [ABSTRACT FROM AUTHOR]

Piezoelectric micromachined ultrasonic transducers (pMUTs) are of great interest for numerous applications, including fingerprint imaging, precise acoustic sensing, and ultrasonic medical imaging, due to their properties of high design freedom and low power consumption when miniaturized for a transducer array. However, micromachined transducers tend to have relatively low acoustic intensity compared with conventional ceramic-based transducers. Therefore, it is preferable and recommended to achieve high acoustic intensity and enhanced displacement of the pMUTs. This paper presents circular pMUTs with various clamped membranes and explores the displacement and mode shape of membranes at resonance frequencies that are critical for enhanced acoustic intensity. Each circular clamped membrane had four etched holes at the edge of the membrane to control the boundary condition, which affected the resonance frequencies and membrane displacement by controlling the effective stiffness. The displacement and effective area as a function of etching hole size were simulated using COMSOL software and verified experimentally. The maximum displacement of a membrane 60 µm in diameter exhibited a 25% improvement when the etching hole angle was 20° compared with the fully clamped membrane. The effective area for acoustic intensity increased from 54.2% to 61.7% at 60° when the mode shape changed from circular to square. The experimental and simulation results were in reasonable agreement, and the results helped clarify how the geometric design of the suspended membrane of the pMUT affects its vibrational characteristics. [Display omitted] • Piezoelectric micromachined ultrasonic transducers (pMUTs) with various etching holes were fabricated using surface micromachining. • The circular and fin-shaped etching holes were used to modify the boundary conditions of the pMUT membrane. • The experimental results for the effect of etching holes on vibrational characteristics agree with the COMSOL simulation results. • The various design of the etching hole provides a method to increase the output pressure of pMUT for ultrasonic application. [ABSTRACT FROM AUTHOR]

Most polymer-based biomedical implantable microscale devices have a smooth surface, so that cell seeding is suppressed in the absence of an adhesive material coating on the surface. SU-8 is a negative photoresist, and is widely used for the fabrication of micro-/nanoscale biomedical devices. A physical surface modification technique was introduced in this study to enhance cell viability and mobility on a SU-8 substrate. To characterize cell viability and mobility, four types of SU-8 substrate were prepared: flat bare substrate, poly- l -lysine (PLL)-coated flat bare substrate, nanoporous substrate, and PLL-coated nanoporous substrate. R at pheochromocytoma (PC12) cells were cultured on these substrates, and nerve growth factor (NGF) was added to induce differentiation of the PC12 cells. On the seventh day of cell culture, PC12 cells on the nanoporous SU-8 substrate showed 24.3% cell differentiation (neurite outgrowth) versus 1.1% cell differentiation on the flat bare substrate. It was also found that cells had a tendency to move from a flat surface to a nanoporous region. These cellular activities on the nanoporous SU-8 substrate suggest that nanopores can be used to regulate cellular activities and can be applied to SU-8-based microscale biomedical devices. [ABSTRACT FROM AUTHOR]

Two types of microfabricated acoustic transducers-the resonator array of isolated beams (RAIB) and the resonator array of coupled beams (RACB)-were built using MEMS technology. The frequency selectivity of the two types of transducers was qualitatively compared using the transfer functions measured with a scanning laser Doppler vibrometer (SLDV). Each RAIB beam operated as a band-pass filter in the proximity to the corresponding resonance frequency, thereby showing the frequency-selective feature of the basilar membrane (BM). However, the frequency selectivity of RACB was poor because the SiO membrane, which mechanically coupled the neighboring beams, suppressed the independent response of each beam. The influence of the mechanical coupling of the SiO membrane was simulated using lumped parametric models. Simulation results showed that the coupling stiffness of the SiO membrane may significantly undermine the frequency selectivity of the resonator array. The comparison of the frequency-selective performance revealed that RAIB is a better option than RACB for mimicking the tonotopy of BM. [ABSTRACT FROM AUTHOR]

Microelectromechanical system (MEMS) test sockets with attached tips were developed for a ball-grid-array integrated circuit (BGA IC) package, using MEMS fabrication technology in conjunction with Ni-Co electroplating and XeF isotropic silicon etching. The electroplating process was used to create metal tips and thick metal cantilevers, which increased the contact reliability and conductivity. XeF isotropic silicon etching was used to release the cantilever array, which reduced the process cost and increased the mechanical stability. A finite element analysis (FEA) simulation was conducted to verify the force-deflection relationships of five types of cantilevers with attached tips. With an input deflection of 40 μm, the measured forces ranged from 12.55 to 26.14 mN, and matched the FEA results. The path resistance between a tip and the appropriate electrode pad was less than 3.49 Ω for all cantilevers when the tips were connected to the corresponding positions with more than 5 mN of contact force. The cantilever design with a length of 430 um and a tip height of 60 um (L430D60) showed the best performance in terms of the force-deflection relationship, a well as resistance. Therefore, the fabricated MEMS test sockets with tips are potentially applicable to actual BGA IC package tests. [ABSTRACT FROM AUTHOR]

Animals detect and discriminate countless environmental chemicals for their well-being and survival. Although a single chemical can trigger opposing behavioral responses depending on its concentration, the mechanisms underlying such a concentration-dependent switching remain poorly understood. Here, we show that C. elegans exhibits either attraction or avoidance of the bacteria-derived volatile chemical dimethyl trisulfide (DMTS) depending on its concentration. This behavioral switching is mediated by two different types of chemosensory neurons, both of which express the DMTS-sensitive seven-transmembrane G protein-coupled receptor (GPCR) SRI-14. These two sensory neurons share downstream interneurons that process and translate DMTS signals via distinct glutamate receptors to generate the appropriate behavioral outcome. Thus, our results present one mechanism by which an animal connects two distinct types of chemosensory neurons detecting a common ligand to alternate downstream circuitry, thus efficiently switching between specific behavioral programs based on ligand concentration. [Display omitted] • C. elegans detects the bacteria-derived organic compound DMTS via a SRI-14 GPCR • This single GPCR mediates a DMTS concentration-dependent behavioral switching • SRI-14 is expressed in two different sensory neuron types • Glutamatergic signals mediate DMTS concentration-dependent behavioral switching Choi et al. show that C. elegans detects the volatile bacteria-derived organic compound DMTS via the SRI-14 GPCR, which is both necessary and sufficient to mediate a concentration-dependent behavioral switching in response to DMTS. [ABSTRACT FROM AUTHOR]

• A piezoelectric MEMS vector sensor with a cross-shaped beam and a mushroom-shaped mass was fabricated. • The crossed-shaped beam has well deposited piezoelectric thin film. • The directivity of the sensor was mechanically characterized from dipole patterns in x- and y -directions. • Finite element analysis was performed with air and underwater conditions to determine the dipole pattern. [Display omitted] Vector hydrophones based on a micro-electro-mechanical system (MEMS) hold great promise for underwater communications, due to their potential for miniaturization and mass production. Piezoelectric materials have recently been utilized in the fabrication of MEMS-based vector hydrophones, as less power is typically required for their operation. Here, we propose a millimeter-scale piezoelectric MEMS vector sensor with a suspended cross-shaped beam and a mushroom-shaped proof mass configuration. This design was inspired by the bio-transducer of the lateral line of fish. Sensor fabrication involved piezoelectric Pb(Zr 0.52 Ti 0.48)O 3 thin-film deposition by radio-frequency magnetron sputtering onto the beam structure, followed by a multi-etching process and assembly using a three-axis microassembly technique. The fabricated MEMS vector sensor showed a resonance frequency above the working frequency range, which was suitable for naval applications. The directivity of the proposed sensor was determined by dipole patterns in the x and y directions, with a maximum relative sensitivity difference of −42 dB at 1 kHz. Finite element analysis results for the resonance frequency and directivity were in good agreement with the experimental results, suggesting that the proposed vector sensor could be used in underwater communications as a vector hydrophone. [ABSTRACT FROM AUTHOR]

[Display omitted] • Preparation of PVDF-based polymers with quaternary ammonium or quaternary pyridinium groups. • The polymers show the antimicrobial rates of >99.99% against S. aureus , E. coli , and C. albicans. • Polymer blends of small amounts of the polymers (i.e. 1 wt%, 5 wt%) and pristine PVDF. • The blends exhibit enhanced film properties compared with pristine PVDF without phase separation. • The blend films have higher antimicrobial performances and excellent biocompatibility. Poly(vinylidene fluoride) (PVDF) and its copolymers have been extensively utilized owing to their fascinating properties such as thermal stability, chemical resistance, and mechanical robustness. However, their lack of microbial resistance is considered a drawback that limits their adoption as biomedical materials. In this study, to overcome this problem, PVDF-based antimicrobial polymers were prepared by grafting quaternary ammonium or quaternary pyridinium monomers. The polymers could effectively kill gram-positive S. aureus , gram-negative E. coli , and the pathogenic yeast C. albicans (antimicrobial rates > 99.99%). Using the polymer blending method, 1 wt% or 5 wt% of the polymers were added to the pristine PVDF film to provide antimicrobial properties. The blend films exhibited enhanced mechanical properties compared to those of pristine PVDF and notably higher antimicrobial performances (>99% for Blend-Q4VP-5); moreover, they were all biocompatible. [ABSTRACT FROM AUTHOR]

Peripheral vascular interventions (PVIs) offer several benefits to patients with lower extremity arterial diseases, including reduced pain, simpler anesthesia, and shorter recovery time, compared to open surgery. However, to monitor the endovascular tools inside the body, PVIs are conducted under X-ray fluoroscopy, which poses serious long-term health risks to physicians and patients. Shortwave infrared (SWIR) imaging of quantum dots (QDs) has shown great potential in bioimaging due to the non-ionizing penetration of SWIR light through tissues. In this paper, a QD-based magnetic guidewire and its system is introduced that allows X-ray-free detection under SWIR imaging and precise steering via magnetic manipulation. The QD magnetic guidewire contains a flexible silicone tube encapsulating a QD polydimethylsiloxane (PDMS) composite, where HgCdSe/HgS/CdS/CdZnS/ZnS/SiO 2 core/multi-shell QDs are dispersed in the PDMS matrix for SWIR imaging upon near-infrared excitation, as well as a permanent magnet for magnetic steering. The SWIR penetration of the QD magnetic guidewire is investigated within an artificial tissue model (1% Intralipid) and explore the potential for non-fluoroscopic PVIs within a vascular phantom model. The QD magnetic guidewire is biocompatible in its entirety, with excellent resistance to photobleaching and chemical alteration, which is a promising sign for its future clinical implementation., (© 2024 Wiley‐VCH GmbH.)

A spiral-artificial basilar membrane (S-ABM) sensor is reported that mimics the basilar membrane (BM) of the human cochlea and can detect sound by separating it into 24 sensing channels based on the frequency band. For this, an analytical function is proposed to design the width of the BM so that the frequency bands are linearly located along the length of the BM. To fabricate the S-ABM sensor, a spiral-shaped polyimide film is used as a vibrating membrane, with maximum displacement at locations corresponding to specific frequency bands of sound, and attach piezoelectric sensor modules made of poly(vinylidene fluoride-trifluoroethylene) film on top of the polyimide film to measure the vibration amplitude at each channel location. As the result, the S-ABM sensor implements a characteristic frequency band of 96-12,821 Hz and 24-independent critical bands. Using real-time signals from discriminate channels, it is demonstrated that the sensor can rapidly identify the operational noises from equipment processes as well as vehicle sounds from environmental noises on the road. The sensor can be used in a variety of applications, including speech recognition, dangerous situation recognition, hearing aids, and cochlear implants, and more., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Although the number of patients with eye diseases is increasing, efficient drug delivery to the posterior segment of the eyeball remains challenging. The reasons include the unique anatomy of the eyeball, the blood-aqueous barrier, the blood-retina barrier, and drug elimination via the anterior chamber and uveoscleral routes. Solutions to these obstacles for therapeutic delivery to the posterior segment will increase the efficacy, efficiency, and safety of ophthalmic treatment. Micro/nanorobots are promising tools to deliver therapeutics to the retina under the direction of an external magnetic field. Although many groups have evaluated potential uses of micro/nanorobots in retinal treatment, most experiments have been performed under idealized in vitro laboratory conditions and thus do not fully demonstrate the clinical feasibility of this approach. This study examined the use of magnetic nanoparticles (MNPs) to deliver dexamethasone, a drug widely used in retinal disease treatment. The MNPs allowed sustainable drug release and successful magnetic manipulation inside bovine vitreous humor and the vitreous humor of living rabbits. Therefore, controlled drug distribution via magnetic manipulation of MNPs is a promising strategy for targeted drug delivery to the retina., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In individuals with hearing loss, protection of residual hearing is essential following cochlear implantation to facilitate acoustic and electric hearing. Hearing preservation requires slow insertion, atraumatic electrode and delivery of the optimal quantity of a pharmacological agent. Several studies have reported variable hearing outcomes with osmotic pump-mediated steroid delivery. New drugs, such as sialyllactose (SL) which have anti-inflammatory effect in many body parts, can prevent tissue overgrowth. In the present study, the positive effects of the pharmacological agent SL against insults were evaluated in vitro using HEI-OC1 cells. An animal model to simulate the damage due to electrode insertion during cochlear implantation was used. SL was delivered using osmotic pumps to prevent loss of the residual hearing in this animal model. Hearing deterioration, tissue fibrosis and ossification were confirmed in this animal model. Increased gene expressions of inflammatory cytokines were identified in the cochleae following dummy electrode insertion. Following the administration of SL, insertion led to a decrease in hearing threshold shifts, tissue reactions, and inflammatory markers. These results emphasize the possible role of SL in hearing preservation and improve our understanding of the mechanism underlying hearing loss after cochlear implantation., (© 2024. The Author(s).)

Cd x Hg 1- x Se/HgS/Cd y Zn 1- y S core/multi-shell quantum dots (QDs) exhibiting bright tissue-penetrating shortwave infrared (SWIR; 1000-1700 nm) photoluminescence (PL) are engineered. The new structure consists of a quasi-type-II Cd x Hg 1- x Se/HgS core/inner shell domain creating luminescent bandgap tunable across SWIR window and a wide-bandgap Cd y Zn 1- y S outer shell boosting the PL quantum yield (QY). This compositional sequence also facilitates uniform and coherent shell growth by minimizing interfacial lattice mismatches, resulting in high QYs in both organic (40-80%) and aqueous (20-70%) solvents with maximum QYs of 87 and 73%, respectively, which are comparable to those of brightest visible-to-near infrared QDs. Moreover, they maintain bright PL in a photocurable resin (QY 40%, peak wavelength ≈ 1300 nm), enabling the fabrication of SWIR-luminescent composites of diverse morphology and concentration. These composites are used to localize controlled amounts of SWIR QDs inside artificial (Intralipid) and porcine tissues and quantitatively evaluate the applicability as luminescent probes for deep-tissue imaging., (© 2023 Wiley-VCH GmbH.)

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely employed in biomedical fields, including targeted delivery of antitumor therapy. Conventional magnetic tumor targeting has used simple static magnetic fields (SMFs), which cause SPIONs to linearly aggregate into a long chain-like shape. Such agglomeration greatly hinders the intracellular targeting of SPIONs into tumors, thus reducing the therapeutic efficacy. In this study, we investigated the enhancement of the intracellular uptake of SPIONs through the application of rotating magnetic fields (RMFs). Based on the physical principles of SPION chain disassembly, we investigated physical parameters to predict the chain length favorable for intracellular uptake. Our prediction was validated by clear visualization of the intracellular distributions of SPIONs in tumor cells at both cellular and three-dimensional microtissue levels. To identify the potential therapeutic effects of enhanced intracellular uptake, magnetic hyperthermia as antitumor therapy was investigated under varying conditions of magnetic hyperthermia and RMFs. The results showed that enhanced intracellular uptake reduced magnetic hyperthermia time and strength as well as particle concentration. The proposed method will be useful in the development of techniques to determine the optimized physical conditions for the enhanced intracellular uptake of SPIONs in antitumor therapy.

Functional restoration by the re-establishment of cellular or neural connections remains a major challenge in targeted cell therapy and regenerative medicine. Recent advances in magnetically powered microrobots have shown potential for use in controlled and targeted cell therapy. In this study, a magnetic neurospheroid (Mag-Neurobot) that can form both structural and functional connections with an organotypic hippocampal slice (OHS) is assessed using an ex vivo model as a bridge toward in vivo application. The Mag-Neurobot consists of hippocampal neurons and superparamagnetic nanoparticles (SPIONs); it is precisely and skillfully manipulated by an external magnetic field. Furthermore, the results of patch-clamp recordings of hippocampal neurons indicate that neither the neuronal excitabilities nor the synaptic functions of SPION-loaded cells are significantly affected. Analysis of neural activity propagation using high-density multi-electrode arrays shows that the delivered Mag-Neurobot is functionally connected with the OHS. The applications of this study include functional verification for targeted cell delivery through the characterization of novel synaptic connections and the functionalities of transported and transplanted cells. The success of the Mag-Neurobot opens up new avenues of research and application; it offers a test platform for functional neural connections and neural regenerative processes through cell transplantation., (© 2023 Wiley-VCH GmbH.)

Dopamine (DA) homeostasis influences emotions, neural circuit development, cognition, and the reward system. Dysfunctions in DA regulation can lead to neurological disorders, including depression, developmental disorders, and addiction. DA homeostasis disruption is a primary cause of Parkinson's Disease (PD). Therefore, understanding the relationship between DA homeostasis and PD progression may clarify the mechanisms for pharmacologically treating PD. This study developed a novel in vitro DA homeostasis platform which consists of three main parts: (1) a microfluidic device for culturing DAergic neurons, (2) an optical detection system for reading DA levels, and (3) an automatic closed-loop control system that establishes when and how much medication to infuse; this uses a microfluidic device that can cultivate DAergic neurons, perfuse solutions, perform in vitro PD modeling, and continuously monitor DA concentrations. The automatically controlled closed-loop control system simultaneously monitors pharmacological PD treatment to support long-term monitoring of DA homeostasis. SH-SY5Y neuroblastoma cells were chosen as DAergic neurons. They were cultivated in the microfluidic device, and real-time cellular DA level measurements successfully achieved long-term monitoring and modulation of DA homeostasis. When applied in combination with multiday cell culture, this advanced system can be used for drug screening and fundamental biological studies.

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., (© 2023. The Author(s).)

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.

Robotic magnetic manipulation systems offer a wide range of potential benefits in medical fields, such as precise and selective manipulation of magnetically responsive instruments in difficult-to-reach vessels and tissues. However, more preclinical/clinical studies are necessary before robotic magnetic interventional systems can be widely adopted. In this study, a clinically translatable, electromagnetically controllable microrobotic interventional system (ECMIS) that assists a physician in remotely manipulating and controlling microdiameter guidewires in real time, is reported. The ECMIS comprises a microrobotic guidewire capable of active magnetic steering under low-strength magnetic fields, a human-scale electromagnetic actuation (EMA) system, a biplane X-ray imaging system, and a remote guidewire/catheter advancer unit. The proposed ECMIS demonstrates targeted real-time cardiovascular interventions in vascular phantoms through precise and rapid control of the microrobotic guidewire under EMA. Further, the potential clinical effectiveness of the ECMIS for real-time cardiovascular interventions is investigated through preclinical studies in coronary, iliac, and renal arteries of swine models in vivo, where the magnetic steering of the microrobotic guidewire and control of other ECMIS modules are teleoperated by operators in a separate control booth with X-ray shielding. The proposed ECMIS can help medical physicians optimally manipulate interventional devices such as guidewires under minimal radiation exposure., (© 2022 Wiley-VCH GmbH.)

A great deal of research has focused on small-scale robots for biomedical applications and minimally invasive delivery of therapeutics (e.g., cells, drugs, and genes) to a target area. Conventional fabrication methods, such as two-photon polymerization, can be used to build sophisticated micro- and nanorobots, but the long fabrication cycle for a single microrobot has limited its practical use. This study proposes a biodegradable spherical gelatin methacrylate (GelMA) microrobot for mass production in a microfluidic channel. The proposed microrobot is fabricated in a flow-focusing droplet generator by shearing a mixture of GelMA, photoinitiator, and superparamagnetic iron oxide nanoparticles (SPIONs) with a mixture of oil and surfactant. Human nasal turbinate stem cells (hNTSCs) are loaded on the GelMA microrobot, and the hNTSC-loaded microrobot shows precise rolling motion in response to an external rotating magnetic field. The microrobot is enzymatically degraded by collagenase, and released hNTSCs are proliferated and differentiated into neuronal cells. In addition, the feasibility of the GelMA microrobot as a cell therapeutic delivery system is investigated by measuring electrophysiological activity on a multielectrode array. Such a versatile and fully biodegradable microrobot has the potential for targeted stem cell delivery, proliferation, and differentiation for stem cell-based therapy., (© 2022 Wiley-VCH GmbH.)

Targeted stem cell delivery with microrobots has emerged as a potential alternative therapeutic strategy in regenerative medicine, and intranasal administration is an effective approach for minimally invasive delivery of therapeutic agents into the brain. In this study, a magnetically powered stem cell-based microrobot ("Cellbot") is used for minimally invasive targeted stem cell delivery to the brain through the intranasal passage. The Cellbot is developed by internalizing superparamagnetic iron oxide nanoparticles (SPIONs) into human nasal turbinate stem cells. The SPIONs have no influence on hNTSC characteristics, including morphology, cell viability, and neuronal differentiation. The Cellbots are capable of proliferation and differentiation into neurons, neural precursor cells, and neurogliocytes. The Cellbots in the microfluidic channel can be reliably manipulated by an external magnetic field for orientation and position control. Using an ex vivo model based on brain organoids, it is determined that the Cellbots can be transplanted into brain tissue. Using a murine model, it is demonstrated that the Cellbots can be intranasally administered and magnetically guided to the target tissue in vivo. This approach has the potential to effectively treat central nervous system disorders in a minimally invasive manner., (© 2021 Wiley-VCH GmbH.)

Biocompatibility and high responsiveness to magnetic fields are fundamental requisites to translate magnetic small-scale robots into clinical applications. The magnetic element iron exhibits the highest saturation magnetization and magnetic susceptibility while exhibiting excellent biocompatibility characteristics. Here, a process to reliably fabricate iron microrobots by means of template-assisted electrodeposition in 3D-printed micromolds is presented. The 3D molds are fabricated using a modified two-photon absorption configuration, which overcomes previous limitations such as the use of transparent substrates, low writing speeds, and limited depth of field. By optimizing the geometrical parameters of the 3D molds, metallic structures with complex features can be fabricated. Fe microrollers and microswimmers are realized that demonstrate motion at ≈20 body lengths per second, perform 3D motion in viscous environments, and overcome higher flow velocities than those of "conventional 3D printed helical microswimmers." The cytotoxicity of these microrobots is assessed by culturing them with human colorectal cancer (HCT116) cells for four days, demonstrating their good biocompatibility characteristics. Finally, preliminary results regarding the degradation of iron structures in simulated gastric acid liquid are provided., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel cell-stimulation system was fabricated using 10 × 29 piezoelectric micromachined ultrasonic transducer (pMUT) arrays for targeted ultrasonic cell stimulation. Both the diameter of a single pMUT element and the edge-to-edge gap were 120 μm, and the size of a pMUT array was 2.27 × 6.84 mm, to be placed at the bottom of a Transwell. The measured resonance frequency of a single pMUT element was 1.48 ± 0.13 MHz and the measured acoustic intensity of the pMUT array was 0.15 ± 0.03 MPa at 1 mm away from the transducer. A pMUT array was mounted on a print circuit board (PCB), which was designed in accordance with the size of a 12-well Transwell. The Transwell was placed on the PCB and wire bonding was performed to electrically connect the PCB and pMUT arrays. After wiring, the PCB and pMUT arrays were coated with 2.6-μm thick parylene-C to ensure biocompatibility and waterproofing. PC12 cells were used for ultrasonic cell stimulation tests to examine the proposed all-in-one low-intensity pulsed ultrasound stimulation system. Various stimulation times and duty cycles were used simultaneously for cell proliferation in a confined cell culture environment. All stimulation groups showed increased cell proliferation rates, in the range 138-166%, versus the proliferation rate of the control group.

Biodegradable polymer droplet containing magnetosome demonstrates active propulsion by magnetic field. Magnetosome is extracted from magnetotactic bacteria, AMB-1. Mixture of magnetosome and sodium alginate composes into droplet using the microfluidic device applied Plateau-Rayleigh instability principle. The magnetosome-contained droplet selects its route at the bifurcate microchannels by magnetic field. This shows tissue targeting potential of the proposed drug delivery system.

Magnetically manipulated microrobots are demonstrated for targeted cell transportation. Full three-dimensional (3D) porous structures are fabricated with an SU-8 photoresist using a 3D laser lithography system. Nickel and titanium are deposited as a magnetic material and biocompatible material, respectively. The fabricated microrobots are controlled in the fluid by external magnetic fields. Human embryonic kidney 239 (HEK 239) cells are cultivated in the microrobot to show the possibility for targeted cell transportation., (© 2013 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)