Untethered robots miniaturized to the length scale of millimeter and below attract growing attention for the prospect of transforming many aspects of health care and bioengineering. As the robot size goes down to the order of a single cell, previously inaccessible body sites would become available for high-resolution in situ and in vivo manipulations. This unprecedented direct access would enable an extensive range of minimally invasive medical operations. Here, we provide a comprehensive review of the current advances in biomedical untethered mobile milli/microrobots. We put a special emphasis on the potential impacts of biomedical microrobots in the near future. Finally, we discuss the existing challenges and emerging concepts associated with designing such a miniaturized robot for operation inside a biological environment for biomedical applications.

Bacteria-propelled biohybrid microswimmers have recently shown to be able to actively transport and deliver cargos encapsulated into their synthetic constructs to specific regions locally. However, usage of synthetic materials as cargo carriers can result in inferior performance in load-carrying efficiency, biocompatibility, and biodegradability, impeding clinical translation of biohybrid microswimmers. Here, we report construction and external guidance of bacteria-driven microswimmers using red blood cells (RBCs; erythrocytes) as autologous cargo carriers for active and guided drug delivery. Multifunctional biohybrid microswimmers were fabricated by attachment of RBCs [loaded with anticancer doxorubicin drug molecules and superparamagnetic iron oxide nanoparticles (SPIONs)] to bioengineered motile bacteria, Escherichia coli MG1655, via biotin-avidin-biotin binding complex. Autonomous and on-board propulsion of biohybrid microswimmers was provided by bacteria, and their external magnetic guidance was enabled by SPIONs loaded into the RBCs. Furthermore, bacteria-driven RBC microswimmers displayed preserved deformability and attachment stability even after squeezing in microchannels smaller than their sizes, as in the case of bare RBCs. In addition, an on-demand light-activated hyperthermia termination switch was engineered for RBC microswimmers to control bacteria population after operations. RBCs, as biological and autologous cargo carriers in the biohybrid microswimmers, offer notable advantages in stability, deformability, biocompatibility, and biodegradability over synthetic cargo-carrier materials. The biohybrid microswimmer design presented here transforms RBCs from passive cargo carriers into active and guidable cargo carriers toward targeted drug and other cargo delivery applications in medicine.

Untethered micron-scale mobile robots can navigate and non-invasively perform specific tasks inside unprecedented and hard-to-reach inner human body sites and inside enclosed organ-on-a-chip microfluidic devices with live cells.

A major challenge for untethered microscale mobile robotics is the control of many agents in the same workspace for distributed operation. In this work, we present a new method to independently control multiple sub-mm microrobots in three dimensions (3D) using magnetic gradient pulling as the 3D motion generation method. Motion differentiation is accomplished through the use of geometrically or magnetically distinct microrobots which assume different magnetization directions in a rotating or oscillating magnetic field. This allows for different magnetic forces to be exerted on each, enabling independent motion control and path following of multiple microrobots along arbitrary 3D trajectories. Path following in 3D with less than 310 μ m mean error is shown for a set of two microrobots of size 350 μ m and 1500 μ m, and independent motions are shown with three microrobots. It is also shown that control of more microrobots could be possible using improved magnetic coil hardware. Microrobot diversity is analyzed with regards to the effect on independent control. The proposed addressability method could be used for the 3D control of a team of microrobots inside microfluidic channels or in the human body for localized therapy or diagnostics.

Existing remotely actuated magnetic microrobots exhibit a maximum of only five-degree-of-freedom (DOF) actuation, as creation of a driving torque about the microrobot magnetization axis is not achievable. This lack of full orientation control limits the effectiveness of existing microrobots for precision tasks of object manipulation and orientation for advanced medical, biological and micromanufacturing applications. This paper presents a magnetic actuation method that allows remotely powered microrobots to achieve full six-DOF actuation by considering the case of a non-uniform magnetization profile within the microrobot body. This non-uniform magnetization allows for additional rigid-body torques to be induced from magnetic forces via a moment arm. A general analytical model presents the working principle for continuous and discrete magnetization profiles, which is applied to permanent or non-permanent (soft) magnet bodies. Several discrete-magnetization designs are also presented which possess reduced coupling between magnetic forces and induced rigid-body torques. Design guidelines are introduced which can be followed to ensure that a magnetic microrobot design is capable of six-DOF actuation. A simple permanent-magnet prototype is fabricated and used to quantitatively demonstrate the accuracy of the analytical model in a constrained-DOF environment and qualitatively for free motion in a viscous liquid three-dimensional environment. Results show that desired forces and torques can be created with high precision and limited parasitic actuation, allowing for full six-DOF actuation using limited feedback control.

We built an out-of-equilibrium material system by designing competing interactions that are both dissipative and programmable.