Abstract
Microcatheters have enabled diverse minimally invasive endovascular operations and notable health benefits compared with open surgeries. However, with tortuous routes far from the arterial ...puncture site, the distal vascular regions remain challenging for safe catheter access. Therefore, we propose a wireless stent-shaped magnetic soft robot to be deployed, actively navigated, used for medical functions, and retrieved in the example M4 segment of the middle cerebral artery. We investigate shape-adaptively controlled locomotion in phantoms emulating the physiological conditions here, where the lumen diameter shrinks from 1.5 mm to 1 mm, the radius of curvature of the tortuous lumen gets as small as 3 mm, the lumen bifurcation angle goes up to 120
°
, and the pulsatile flow speed reaches up to 26 cm/s. The robot can also withstand the flow when the magnetic actuation is turned off. These locomotion capabilities are confirmed in porcine arteries ex vivo. Furthermore, variants of the robot could release the tissue plasminogen activator on-demand locally for thrombolysis and function as flow diverters, initiating promising therapies towards acute ischemic stroke, aneurysm, arteriovenous malformation, dural arteriovenous fistulas, and brain tumors. These functions should facilitate the robot’s usage in new distal endovascular operations.
Wireless magnetic microrobots are envisioned to revolutionize minimally invasive medicine. While many promising medical magnetic microrobots are proposed, the ones using hard magnetic materials are ...not mostly biocompatible, and the ones using biocompatible soft magnetic nanoparticles are magnetically very weak and, therefore, difficult to actuate. Thus, biocompatible hard magnetic micro/nanomaterials are essential toward easy‐to‐actuate and clinically viable 3D medical microrobots. To fill such crucial gap, this study proposes ferromagnetic and biocompatible iron platinum (FePt) nanoparticle‐based 3D microprinting of microrobots using the two‐photon polymerization technique. A modified one‐pot synthesis method is presented for producing FePt nanoparticles in large volumes and 3D printing of helical microswimmers made from biocompatible trimethylolpropane ethoxylate triacrylate (PETA) polymer with embedded FePt nanoparticles. The 30 μm long helical magnetic microswimmers are able to swim at speeds of over five body lengths per second at 200 Hz, making them the fastest helical swimmer in the tens of micrometer length scale at the corresponding low‐magnitude actuation fields of 5–10 mT. It is also experimentally in vitro verified that the synthesized FePt nanoparticles are biocompatible. Thus, such 3D‐printed microrobots are biocompatible and easy to actuate toward creating clinically viable future medical microrobots.
Wireless magnetic microrobots are envisioned to revolutionize minimally invasive medicine, whereas biocompatible magnetic materials for such robots are limited to weak actuation properties. Herein, batch‐synthesized iron‐platinum nanoparticles and two‐photon polymerization are used to 3D print biocompatible helical microswimmers. These microswimmers can swim at speeds over five body lengths per second, making them the fastest helical swimmer in the tens‐of‐micrometer length scale.
Abstract
Manipulating and separating single label-free cells without biomarker conjugation have attracted significant interest in the field of single-cell research, but digital circuitry control and ...multiplexed individual storage of single label-free cells remain a challenge. Herein, by analogy with the electrical circuitry elements and electronical holes, we develop a pseudo-diamagnetophoresis (PsD) mattertronic approach in the presence of biocompatible ferrofluids for programmable manipulation and local storage of single PsD holes and label-free cells. The PsD holes conduct along linear negative micro-magnetic patterns. Further, eclipse diode patterns similar to the electrical diode can implement directional and selective switching of different PsD holes and label-free cells based on the diode geometry. Different eclipse heights and junction gaps influence the switching efficiency of PsD holes for mattertronic circuitry manipulation and separation. Moreover, single PsD holes are stored at each potential well as in an electrical storage capacitor, preventing multiple occupancies of PsD holes in the array of individual compartments due to magnetic Coulomb-like interaction. This approach may enable the development of large programmable arrays of label-free matters with high throughput, efficiency, and reliability as multiplex cell research platforms.
Acoustically‐driven bubbles at the micron scale can generate strong microstreaming flows in its surrounding fluidic medium. The tunable acoustic streaming strength of oscillating microbubbles and the ...diversity of the generated flow patterns enable the design of fast‐moving microrobots with multimodal locomotion suitable for biomedical applications. The acoustic microrobots holding two coupled microbubbles inside a rigid body are presented; trapped bubbles inside the L‐shaped structure with different orifices generate various streaming flows, thus allowing multiple degrees of freedom in locomotion. The streaming pattern and mean streaming speed depend on the intensity and frequency of the acoustic wave, which can trigger four dominant locomotion modes in the microrobot, denoted as translational and rotational, spinning, rotational, and translational modes. Next, the effect of various geometrical and actuation parameters on the control and navigation of the microrobot is investigated. Furthermore, the surface‐slipping multimodal locomotion, flow mixing, particle manipulation capabilities, the effective interaction of high flow rates with cells, and subsequent cancerous cell lysing abilities of the proposed microrobot are demonstrated. Overall, these results introduce a design toolbox for the next generation of acoustic microrobots with higher degrees of freedom with multimodal locomotion in biomedical applications.
Addressing microrobots' limited maneuverability; the acoustically‐powered micron‐scale robots with microorganism‐inspired motions are developed. These robots house two coupled microbubbles that create complex acoustic‐streaming yielding various flow patterns and allowing the microrobots to move swiftly. These microrobots have proven to excel in multimodal locomotion, flow mixing, and cell lysing, making them ideal for diverse biomedical uses.
Microrobots offer transformative solutions for non‐invasive medical interventions due to their small size and untethered operation inside the human body. However, they must face the immune system as ...a natural protection mechanism against foreign threats. Here, non‐immunogenic stealth zwitterionic microrobots that avoid recognition from immune cells are introduced. Fully zwitterionic photoresists are developed for two‐photon polymerization 3D microprinting of hydrogel microrobots with ample functionalization: tunable mechanical properties, anti‐biofouling and non‐immunogenic properties, functionalization for magnetic actuation, encapsulation of biomolecules, and surface functionalization for drug delivery. Stealth microrobots avoid detection by macrophage cells of the innate immune system after exhaustive inspection (>90 hours), which has not been achieved in any microrobotic platform to date. These versatile zwitterionic materials eliminate a major roadblock in the development of biocompatible microrobots, and will serve as a toolbox of non‐immunogenic materials for medical microrobot and other device technologies for bioengineering and biomedical applications.
Zwitterionic stealth microrobots avoid detection and capture by immune cells. Zwitterionic microrobots with anti‐biofouling, stealth, and non‐immunogenic properties are 3D‐printed via two‐photon‐polymerization, and are functionalized for magnetic actuation, encapsulation of biomolecules, and drug delivery. The microrobots remain undetected by macrophages and other immune cells for at least 90 hours, overcoming a major roadblock in medical microrobotics.
In article number 2003013, Salvador Borros, Metin Sitti, and co‐workers report stealth microrobots that can operate covertly under the immune system's radar. These stealth microrobots, fabricated ...from custom zwitterionic polymers for 3D microprinting, remain undetected by immune cells after exhaustive inspection, thus avoiding phagocytosis
and immune clearance.
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 µm 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‐α, 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.
Live immune cell‐derived microrobots from macrophages, i.e., immunobots, combine robotic mobility control and immunomodulatory functions on immune cells: i) stimulating and sustaining macrophages toward the anti‐tumorigenic phenotypes and ii) controlling their direction of rolling motion precisely using an external magnetic field. The immunobot fabrication process is highly efficient (≈99.2%) and maintains durable anti‐tumorigenic phenotypes, where the immunobots exhibit significant anticancer activity in mouse urinary bladder cancer cells.
Magnetic Microrobots
In article number 2000204, Metin Sitti and co‐workers demonstrate a 3D microprinted helical structure with embedded iron platinum (FePt) nanoparticles. These biocompatible ...helical microswimmers can swim over five body lengths per second, making them the fastest helical swimmer in the tens of micrometer scale.
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