Design and Development of a Lorentz Force-Based MRI-Driven Neuroendoscope

The introduction of neuroendoscopy, microneurosurgery, neuronavigation, and intraoperative imaging for surgical operations has made significant improvements over other traditionally invasive surgical techniques. The integration of magnetic resonance imaging (MRI)-driven surgical devices with intraoperative imaging and endoscopy can enable further advancements in surgical treatments and outcomes. This work proposes the design and development of an MRI-driven endoscope leveraging the high (3-7 T), external magnetic field of an MR scanner for heat-mitigated steering within the ventricular system of the brain. It also demonstrates the effectiveness of a Lorentz force-based grasper for diseased tissue manipulation and ablation. Feasibility studies show the neuroendoscope can be steered precisely within the lateral ventricle to locate a tumor using both MRI and endoscopic guidance. Results also indicate grasping forces as high as 31 mN are possible and power inputs as low as 0.69 mW can cause cancerous tissue ablation. These findings enable further developments of steerable devices using MR imaging integrated with endoscopic guidance for improved outcomes

Pangolin-inspired untethered magnetic robot for on-demand biomedical heating applications

Abstract Untethered magnetic miniature soft robots capable of accessing hard-to-reach regions can enable safe, disruptive, and minimally invasive medical procedures. However, the soft body limits the integration of non-magnetic external stimuli sources on the robot, thereby restricting the functionalities of such robots. One such functionality is localised heat generation, which requires solid metallic materials for increased efficiency. Yet, using these materials compromises the compliance and safety of using soft robots. To overcome these competing requirements, we propose a pangolin-inspired bi-layered soft robot design. We show that the reported design achieves heating > 70 °C at large distances > 5 cm within a short period of time <30 s, allowing users to realise on-demand localised heating in tandem with shape-morphing capabilities. We demonstrate advanced robotic functionalities, such as selective cargo release, in situ demagnetisation, hyperthermia and mitigation of bleeding, on tissue phantoms and ex vivo tissues

Broad-Wavelength Light-Driven High-Speed Hybrid Crystal Actuators Actuated Inside Tissue-Like Phantoms

Research on molecular crystals exhibiting light-driven actuation has made remarkable progress through the development of various molecules and the identification of driving mechanisms. However, crystals developed to date have been driven mainly by ultraviolet (UV) or blue light irradiation, and driving by red or near-infrared (NIR) light has not been attempted yet. Herein, a broad-wavelength light-driven molecular crystals that exhibit high-speed bending by photothermal effect is developed. Titanium carbide (Ti₃C₂Tₓ) MXene nanosheets are integrated into salicylideneaniline crystals to extend the wavelength range that causes photothermally driven bending to UV, visible, and NIR light. In addition, unlike the thin pristine molecular crystals that show slow photoisomerization-induced bending only under UV light, the MXene layer enables the molecular crystals to be actuated rapidly regardless of their thickness over a wide range of wavelengths. The hybridization of molecular crystals with MXene, which exhibits strong biocompatibility as well as NIR light-driven photothermal effect, allows for the bending of the hybrid crystals inside agar phantoms mimicking biological tissue. Last, it is confirmed that MXene hybridization can be extended to common molecular crystals including various salicylideneaniline and anisole derivatives.ISSN:1616-3028ISSN:1616-301

Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery

Bacterial biohybrids, composed of self-propelling bacteria carrying micro/nanoscale materials, can deliver their payload to specific regions under magnetic control, enabling additional frontiers in minimally invasive medicine. However, current bacterial biohybrid designs lack high-throughput and facile construction with favorable cargoes, thus underperforming in terms of propulsion, payload efficiency, tissue penetration, and spatiotemporal operation. Here, we report magnetically controlled bacterial biohybrids for targeted localization and multistimuliresponsive drug release in three-dimensional (3D) biological matrices. Magnetic nanoparticles and nanoliposomes loaded with photothermal agents and chemotherapeutic molecules were integrated onto Escherichia coli with ~90% efficiency. Bacterial biohybrids, outperforming previously reported E. coli–based microrobots, retained their original motility and were able to navigate through biological matrices and colonize tumor spheroids under magnetic fields for on-demand release of the drug molecules by near-infrared stimulus. Our work thus provides a multifunctional microrobotic platform for guided locomotion in 3D biological networks and stimuli-responsive delivery of therapeutics for diverse medical applications.ISSN:2375-254

Remotely Guided Immunobots Engaged in Anti-Tumorigenic Phenotypes for Targeted Cancer Immunotherapy

Building medical microrobots from the body's own cells may circumvent the biocompatibility concern and hence presents more potential in clinical applications to improve the possibility of escaping from the host defense mechanism. More importantly, live cells can enable therapeutically relevant functions with significantly higher efficiency than synthetic systems. Here, live immune cell-derived microrobots from macrophages, i.e., immunobots, which can be remotely steered with externally applied magnetic fields and directed toward anti-tumorigenic (M1) phenotypes, are presented. Macrophages engulf the engineered magnetic decoy bacteria, composed of 0.5 mu m diameter silica Janus particles with one side coated with anisotropic FePt magnetic nanofilm and the other side coated with bacterial lipopolysaccharide (LPS). This study demonstrates the torque-based surface rolling locomotion of the immunobots along assigned trajectories inside blood plasma, over a layer of endothelial cells, and under physiologically relevant flow rates. The immunobots secrete signature M1 cytokines, IL-12 p40, TNF-alpha, and IL-6, and M1 cell markers, CD80 and iNOS, via toll-like receptor 4 (TLR4)-mediated stimulation with bacterial LPS. The immunobots exhibit anticancer activity against urinary bladder cancer cells. This study further demonstrates such immunobots from freshly isolated primary bone marrow-derived macrophages since patient-derivable macrophages may have a strong clinical potential for future cell therapies in cancer.ISSN:1613-6810ISSN:1613-682

Multifunctional 3D-Printed Pollen Grain-Inspired Hydrogel Microrobots for On-Demand Anchoring and Cargo Delivery

While a majority of wireless microrobots have shown multi-responsiveness to implement complex biomedical functions, their functional executions are strongly dependent on the range of stimulus inputs, which curtails their functional diversity. Furthermore, their responsive functions are coupled to each other, which results in the overlap of the task operations. Here, a 3D-printed multifunctional microrobot inspired by pollen grains with three hydrogel components is demonstrated: iron platinum (FePt) nanoparticle-embedded pentaerythritol triacrylate (PETA), poly N-isopropylacrylamide (pNIPAM), and poly N-isopropylacrylamide acrylic acid (pNIPAM-AAc) structures. Each of these structures exhibits their respective targeted functions: responding to magnetic fields for torque-driven surface rolling and steering, exhibiting temperature responsiveness for on-demand surface attachment (anchoring), and pH-responsive cargo release. The versatile multifunctional pollen grain-inspired robots conceptualized here pave the way for various future medical microrobots to improve their projected performance and functional diversity.ISSN:0935-9648ISSN:1521-409

Parameters Influencing Gene Delivery Efficiency of PEGylated Chitosan Nanoparticles: Experimental and Modeling Approach

Experimentation of nanomedicine is labor-intensive, time-consuming, and requires costly laboratory consumables. Constructing a reliable mathematical model for such systems is also challenging due to the difficulties in gathering a sufficient number of data points. Artificial neural networks (ANNs) are indicated as an efficient approach in nanomedicine to investigate the cause-effect relationships and predict output variables. Herein, an ANN is adapted into plasmid DNA (pDNA) encapsulated and PEGylated chitosan nanoparticles cross-linked with sodium tripolyphosphate (TPP) to investigate the effects of critical parameters on the transfection efficiencies of nanoparticles. The ANN model is developed based on experimental results with three independent input variables: 1) polyethylene glycol (PEG) molecular weight, 2) PEG concentration, and 3) nanoparticle concentration, along with one output variable as a percentage of green fluorescent protein (GFP) expression, which refers to transfection efficiency. The constructed model is further validated with the leave-p-out cross-validation method. The results indicate that the developed model has good prediction capability and is influential in capturing the transfection efficiencies of different nanoparticle groups. Overall, this study reveals that the ANN could be an efficient tool for nanoparticle-mediated gene delivery systems to investigate the impacts of critical parameters in detail with reduced experimental effort and cost.ISSN:2699-930

High-Performance Magnetic FePt (L1(0)) Surface Microrollers Towards Medical Imaging-Guided Endovascular Delivery Applications

Controlled microrobotic navigation in the vascular system can revolutionize minimally invasive medical applications, such as targeted drug and gene delivery. Magnetically controlled surface microrollers have emerged as a promising microrobotic platform for controlled navigation in the circulatory system. Locomotion of micrororollers in strong flow velocities is a highly challenging task, which requires magnetic materials having strong magnetic actuation properties while being biocompatible. The L1(0)-FePt magnetic coating can achieve such requirements. Therefore, such coating has been integrated into 8 mu m-diameter surface microrollers and investigated the medical potential of the system from magnetic locomotion performance, biocompatibility, and medical imaging perspectives. The FePt coating significantly advanced the magnetic performance and biocompatibility of the microrollers compared to a previously used magnetic material, nickel. The FePt coating also allowed multimodal imaging of microrollers in magnetic resonance and photoacoustic imaging in ex vivo settings without additional contrast agents. Finally, FePt-coated microrollers showed upstream locomotion ability against 4.5 cm s(-1) average flow velocity with real-time photoacoustic imaging, demonstrating the navigation control potential of microrollers in the circulatory system for future in vivo applications. Overall, L1(0)-FePt is conceived as the key material for image-guided propulsion in the vascular system to perform future targeted medical interventions.ISSN:1616-3028ISSN:1616-301