Biohybrid bacteria–based microrobots are increasingly recognized as promising externally controllable vehicles for targeted cancer therapy. Magnetic fields in particular have been used as a safe means to transfer energy and direct their motion. Thus far, the magnetic control strategies used in this context rely on poorly scalable magnetic field gradients, require active position feedback, or are ill-suited to diffuse distributions within the body. Here, we present a magnetic torque–driven control scheme for enhanced transport through biological barriers that complements the innate taxis toward tumor cores exhibited by a range of bacteria, shown for Magnetospirillum magneticum as a magnetically responsive model organism. This hybrid control strategy is readily scalable, independent of position feedback, and applicable to bacterial microrobots dispersed by the circulatory system. We observed a fourfold increase in translocation of magnetically responsive bacteria across a model of the vascular endothelium and found that the primary mechanism driving increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a three-dimensional tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated that our control scheme offers further advantages, including the possibility for closed-loop optimization based on inductive detection, as well as spatially selective actuation to reduce off-target effects. Last, after systemic intravenous injection in mice, we showed significantly increased bacterial tumor accumulation, supporting the feasibility of deploying this control scheme clinically for magnetically responsive biohybrid microrobots.

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Published In

Science Robotics
Volume 7 | Issue 71
October 2022

Submission history

Received: 11 January 2022
Accepted: 3 October 2022


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We thank the EPIC RCHCI staff and management and the ETHZ animal welfare officers for their great support with animal experiments. We also thank the Scientific Center for Optical and Electron Microscopy (ScopeM) and the Flow Cytometry Core Facility at ETH-Zürich for access to facilities. We thank D. C. Bono for useful input for the magnetometer design, L. Amoudruz for helpful discussions on computational modeling of MTB, L. Stöcklin for assistance with the inductive detection experiments, and D. Dubey for providing helpful feedback on the manuscript.
Funding: This work is supported by the Branco Weiss Fellowship—Society in Science (title: “Cancer-fighting magnetic biobots: Harnessing the power of synthetic biology and magnetism”) and funding from Takeda Pharmaceuticals (title: “Feasibility study: Penetration ability of magnetotactic bacteria”). T.G. was supported by a Swiss Government Excellence Scholarship.
Author contributions: Conceptualization: S.S., T.G., N.M., M.G.C., and V.L. Methodology: S.S., T.G., N.M., and M.G.C. Investigation: T.G., N.M., M.G.C., T.T.N., and S.S. Visualization: T.G. Supervision: S.S. Writing—original draft: T.G. Writing—review and editing: S.S., T.G., M.G.C., N.M., T.T.N., and V.L.
Competing interests: S.S. is co-founder, technical advisor, and member of the board of MagnebotiX AG and member of the board of Quercis Pharma. AG. V.L. is an employee of Takeda Pharmaceuticals. The authors declare that they have no other competing interests.
Data and materials availability: All data needed to support the conclusions of this manuscript are included in the main text or Supplementary Materials. Additional data related to this paper may be requested from the authors.



Department of Health Sciences and Technology, Institute for Translational Medicine, ETH Zürich, 8092 Zürich, Switzerland.
Roles: Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, and Writing - review & editing.
N. Mirkhani
Department of Health Sciences and Technology, Institute for Translational Medicine, ETH Zürich, 8092 Zürich, Switzerland.
Roles: Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, and Writing - review & editing.
Department of Health Sciences and Technology, Institute for Translational Medicine, ETH Zürich, 8092 Zürich, Switzerland.
Roles: Conceptualization, Formal analysis, Investigation, Methodology, Software, Visualization, and Writing - review & editing.
Department of Health Sciences and Technology, Institute for Translational Medicine, ETH Zürich, 8092 Zürich, Switzerland.
Roles: Formal analysis, Investigation, Methodology, Validation, and Writing - review & editing.
Present address: Roche Pharma Research and Early Development, Wagistrasse 10, 8952 Schlieren, Switzerland.
V. Ling
Takeda Pharmaceuticals, 40 Landsdowne St., Cambridge, MA 02139, USA.
Roles: Conceptualization, Funding acquisition, and Visualization.
Department of Health Sciences and Technology, Institute for Translational Medicine, ETH Zürich, 8092 Zürich, Switzerland.
Roles: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, and Writing - review & editing.

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Corresponding author. Email: [email protected]

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