Spiky Magnetic Microparticles Synthesized from Microrod-Stabilized Pickering Emulsion.

Tailoring the microstructure of magnetic microparticles is of vital importance for their applications. Spiky magnetic particles, such as those made from sunflower pollens, have shown promise in single cell treatment and biofilm removal. Synthetic methods that can replicate or extend the functionality of such spiky particles would be advantageous for their widespread utilization. In this work, a wet-chemical method is introduced for spiky magnetic particles that are templated from microrod-stabilized Pickering emulsions. The spiky morphology is generated by the upright attachment of silica microrods at the oil-water interface of oil droplets. Spiky magnetic microparticles with control over the length of the spikes are obtained by dispersing hydrophobic magnetic nanoparticles in the oil phase and photopolymerizing the monomer. The spiky morphology dramatically enhances colloidal stability of these particles in high ionic strength solutions and physiologic media such as human saliva and saline-based biofilm suspension. To demonstrate their utility, the spiky magnetic particles are applied for magnetically controlled removal of oral biofilms and retrieval of bacteria for diagnostic sampling. This method expands the toolbox for engineering microparticle morphology and could promote the fabrication of functional magnetic microrobots.

Targeting biofilm infections in humans using small scale robotics.

The eradication of drug-resistant microbial biofilms remains an unresolved global health challenge. Small-scale robotics are providing innovative therapeutic and diagnostic approaches with high precision and efficacy. These approaches are rapidly moving from proof-of-concept studies to translational biomedical applications using ex vivo, animal, and clinical models. Here, we discuss the fundamental and translational aspects of how microrobots target the infection sites to disrupt the structural and functional traits of biofilms and their antimicrobial resistance mechanisms. We emphasize current approaches of mechanochemical disruption and on-site drug delivery that are supported by in vivo models and preclinical testing, while also highlighting diagnostics potential. We also discuss clinical translation challenges and provide perspectives for development of microrobotics approaches to combat biofilm infections and biofouling in humans.

Nanozyme-Based Robotics Approach for Targeting Fungal Infection.

Fungal pathogens have been designated by the World Health Organization as microbial threats of the highest priority for global health. It remains a major challenge to improve antifungal efficacy at the site of infection while avoiding off-target effects, fungal spreading, and drug tolerance. Here, a nanozyme-based microrobotic platform is developed that directs localized catalysis to the infection site with microscale precision to achieve targeted and rapid fungal killing. Using electromagnetic field frequency modulation and fine-scale spatiotemporal control, structured iron oxide nanozyme assemblies are formed that display tunable dynamic shape transformation and catalysis activation. The catalytic activity varies depending on the motion, velocity, and shape providing controllable reactive oxygen species (ROS) generation. Unexpectedly, nanozyme assemblies bind avidly to fungal (Candida albicans) surfaces to enable concentrated accumulation and targeted ROS-mediated killing in situ. By exploiting these tunable properties and selective binding to fungi, localized antifungal activity is achieved using in vivo-like cell spheroid and animal tissue infection models. Structured nanozyme assemblies are directed to Candida-infected sites using programmable algorithms to perform precisely guided spatial targeting and on-site catalysis resulting in fungal eradication within 10 min. This nanozyme-based microrobotics approach provides a uniquely effective and targeted therapeutic modality for pathogen elimination at the infection site.

Surface Topography-Adaptive Robotic Superstructures for Biofilm Removal and Pathogen Detection on Human Teeth.

The eradication of biofilms remains an unresolved challenge across disciplines. Furthermore, in biomedicine, the sampling of spatially heterogeneous biofilms is crucial for accurate pathogen detection and precise treatment of infection. However, current approaches are incapable of removing highly adhesive biostructures from topographically complex surfaces. To meet these needs, we demonstrate magnetic field-directed assembly of nanoparticles into surface topography-adaptive robotic superstructures (STARS) for precision-guided biofilm removal and diagnostic sampling. These structures extend or retract at multilength scales (micro-to-centimeter) to operate on opposing surfaces and rapidly adjust their shape, length, and stiffness to adapt and apply high-shear stress. STARS conform to complex surface topographies by entering angled grooves or extending into narrow crevices and "scrub" adherent biofilm with multiaxis motion while producing antibacterial reagents on-site. Furthermore, as the superstructure disrupts the biofilm, it captures bacterial, fungal, viral, and matrix components, allowing sample retrieval for multiplexed diagnostic analysis. We apply STARS using automated motion patterns to target complex three-dimensional geometries of ex vivo human teeth to retrieve biofilm samples with microscale precision, while providing "toothbrushing-like" and "flossing-like" action with antibacterial activity in real-time to achieve mechanochemical removal and multikingdom pathogen detection. This approach could lead to autonomous, multifunctional antibiofilm platforms to advance current oral care modalities and other fields contending with harmful biofilms on hard-to-reach surfaces.

Topological defect-propelled swimming of nematic colloids.

Topological defects on colloids rotating in nematic liquid crystals form far-from-equilibrium structures that perform complex swim strokes in which the defects periodically extend, depin, and contract. These defect dynamics propel the colloid, generating translation from rotation. The swimmer's speed and direction are determined by the topological defect's polarity and extent of elongation. Defect elongation is controlled by a rotating external magnetic field, allowing control over particle trajectories. The swimmers' translational motion relies on broken symmetries associated with lubrication forces between the colloid and the bounding surfaces, line tensions associated with the elongated defect, and anisotropic viscosities associated with the defect elongation adjacent to the colloid. The scattering or effective pair interaction of these swimmers is highly anisotropic, with polarization-dependent dimer stability and motion that depend strongly on entanglement and sharing of their extended defect structures. This research introduces transient, far-from-equilibrium topological defects as a class of virtual functional structures that generate modalities of motion and interaction.

Catalytic antimicrobial robots for biofilm eradication.

Magnetically driven robots can perform complex functions in biological settings with minimal destruction. However, robots designed to damage deleterious biostructures could also have important impact. In particular, there is an urgent need for new strategies to eradicate bacterial biofilms as we approach a post-antibiotic era. Biofilms are intractable and firmly attached structures ubiquitously associated with drug-resistant infections and destruction of surfaces. Existing treatments are inadequate to both kill and remove bacteria leading to reinfection. Here we design catalytic antimicrobial robots (CARs) that precisely and controllably kill, degrade and remove biofilms with remarkable efficiency. CARs exploit iron oxide nanoparticles (NPs) with dual catalytic-magnetic functionality that (i) generate bactericidal free radicals, (ii) breakdown the biofilm exopolysaccharide (EPS) matrix, and (iii) remove the fragmented biofilm debris via magnetic field driven robotic assemblies. We develop two distinct CAR platforms. The first platform, the biohybrid CAR, is formed from NPs and biofilm degradation products. After catalytic bacterial killing and EPS disruption, magnetic field gradients assemble NPs and the biodegraded products into a plow-like superstructure. When driven with an external magnetic field, the biohybrid CAR completely removes biomass in a controlled manner, preventing biofilm regrowth. Biohybrid CARs can be swept over broad swathes of surface or can be moved over well-defined paths for localized removal with microscale precision. The second platform, the 3D molded CAR, is a polymeric soft robot with embedded catalytic-magnetic NPs, formed in a customized 3D printed mold to perform specific tasks in enclosed domains. Vane-shaped CARs remove biofilms from curved walls of cylindrical tubes, and helicoid-shaped CARs drill through biofilm clogs, while simultaneously killing bacteria. In addition, we demonstrate applications of CARs to target highly confined anatomical surfaces in the interior of human teeth. These 'kill-degrade-and-remove' CARs systems could have significant impact in fighting persistent biofilm-infections and in mitigating biofouling of medical devices and diverse surfaces.