A hybrid actuated microrobot using an electromagnetic field and flagellated bacteria for tumor‐targeting therapy

Abstract

In this paper, we propose a new concept for a hybrid actuated microrobot for tumor-targeting therapy. For drug delivery in tumor therapy, various electromagnetic actuated microrobot systems have been studied. In addition, bacteria-based microrobot (so-called bacteriobot), which use tumor targeting and the therapeutic function of the bacteria, has also been proposed for solid tumor therapy. Compared with bacteriobot, electromagnetic actuated microrobot has larger driving force and locomotive controllability due to their position recognition and magnetic field control. However, because electromagnetic actuated microrobot does not have self-tumor targeting, they need to be controlled by an external magnetic field. In contrast, the bacteriobot uses tumor targeting and the bacteria's own motility, and can exhibit self-targeting performance at solid tumors. However, because the propulsion forces of the bacteria are too small, it is very difficult for bacteriobot to track a tumor in a vessel with a large bloodstream. Therefore, we propose a hybrid actuated microrobot combined with electromagnetic actuation in large blood vessels with a macro range and bacterial actuation in small vessels with a micro range. In addition, the proposed microrobot consists of biodegradable and biocompatible microbeads in which the drugs and magnetic particles can be encapsulated; the bacteria can be attached to the surface of the microbeads and propel the microrobot. We carried out macro-manipulation of the hybrid actuated microrobot along a desired path through electromagnetic field control and the micro-manipulation of the hybrid actuated microrobot toward a chemical attractant through the chemotaxis of the bacteria. For the validation of the hybrid actuation of the microrobot, we fabricated a hydrogel microfluidic channel that can generate a chemical gradient. Finally, we evaluated the motility performance of the hybrid actuated microrobot in the hydrogel microfluidic channel. We expect that the hybrid actuated microrobot will be utilized for tumor targeting and therapy in future.

Biohybrid and Bioinspired Magnetic Microswimmers

“…The biological uptake of magnetic material (e.g., artificial magnetotactic bacteria) is not available for all kinds of biohybrids; therefore, it might be necessary to attach them to the fabricated microstructures or, depending on the sizes, the other way round. The possibilities have ranged from mechanical trapping, controlled surface charge and chemistry for adhesion, to selective attachment of bacteria through plasma treatment . Synthetic microswimmers can take advantage of magnetic biocompatible coatings and biodegradable materials that were developed over the last decade, which are essential for the realization of in vivo applications.…”

“…Once the target is reached, for example, a tumor (microscale), the field can be switched off, letting the bacteria motility and chemotaxis take over. The system has been tested in a microfluidic channel, but the final purpose would be in vivo tumor targeting . For now, the systems move on a surface, thus 3D steering and steerability have not been achieved yet.…”

“…As a scale bar, the diameter of the beads is ≈10 µm. Adapted with permission . Copyright 2015, Wiley Periodicals, Inc.. c) A “tetrapod” (tube with four flexible arms for release of the cell) can be applied to sperm cells.…”

Perspectives in flow-based microfluidic gradient generators for characterizing bacterial chemotaxis

“…Recent development of non-flowing gradient generators include static gradients generated by diffusion of molecules through porous nitrocellulose 7 or polyester 38 membranes, agarose hydrogel, 15,39,40 collagen, 10,41 polyethylene glycol (PEG) hydrogels, 42,43 through micro-jet array perfusion channels with minimal flow, 44,45 or through in situ biofabricated biopolymer membranes. 46,47 By restricting convective flow with membranes or hydrogels while allowing diffusion of small molecules to generate chemical gradients, flow-free and diffusion-based static gradient generators are able to decouple cell motion of nonadherent cells from flow.…”

Biohybrid Microtube Swimmers Driven by Single Captured Bacteria

“…Bacteria flagellar motion has been utilized powering microrotors and for the delivery of nanoliposomes, but the largest portion of bacteria‐based biohybrid systems research has investigated bacteria‐driven particle microswimmers, where single or multiple bacteria adhere to a spherical particle and carry it while swimming. For these systems, selective patterning of the particle with metals or plasma etching facilitates bacteria adhesion and consequently improves directional swimming. However, bacteria attachment to a particle induces torque and rotational motion, decreasing the net translational motion .…”