Magnetic Microrobots for In Vivo Cargo Delivery: A Review

Abstract

Magnetic microrobots, with their small size and agile maneuverability, are well-suited for navigating the intricate and confined spaces within the human body. In vivo cargo delivery within the context of microrobotics involves the use of microrobots to transport and administer drugs and cells directly to the targeted regions within a living organism. The principal aim is to enhance the precision, efficiency, and safety of therapeutic interventions. Despite their potential, there is a shortage of comprehensive reviews on the use of magnetic microrobots for in vivo cargo delivery from both research and engineering perspectives, particularly those published after 2019. This review addresses this gap by disentangling recent advancements in magnetic microrobots for in vivo cargo delivery. It summarizes their actuation platforms, structural designs, cargo loading and release methods, tracking methods, navigation algorithms, and degradation and retrieval methods. Finally, it highlights potential research directions. This review aims to provide a comprehensive summary of the current landscape of magnetic microrobot technologies for in vivo cargo delivery. It highlights their present implementation methods, capabilities, and prospective research directions. The review also examines significant innovations and inherent challenges in biomedical applications.

Keywords: biomedicine; in vivo cargo delivery; magnetic microrobot.

Figure 2

Typical magnetic actuation platforms for MMRs. (a,b) Electromagnet array platform offers 5 degrees of freedom (5-DoF) for precise control of MMRs, enabling complex manipulation. (c,d) The coil system for MMR actuation features a rotatable mechanism, simplifying the 2D coil actuation system. Without the rotatable mechanism, an additional set of Maxwell and Helmholtz coils is needed. (e,f) Permanent magnet array actuation system: since permanent magnets cannot vary the magnitude of their magnetic fields, these systems typically require an additional robot to move the permanent magnet array. This movement generates a magnetic field gradient, which is crucial for driving MMRs. Figures adapted with permissions from ref. [48], ACS, (a); ref. [49], Wiley, (b); ref. [41], Elsevier, (c,d); ref. [17], MDPI, (e,f).

Figure 3

Typical structural design of MMRs. (a) The porous helical design of MMRs significantly enhances their magnetism, and thus their controllability in viscous fluids by increasing the surface area. This feature greatly improves cargo loading and release capabilities and magnetic interaction efficiency. (b) Needle and helical design, it can fix to the target organ or tissue. (c) Spherical MMRs possess the unique ability to reconfigure in response to specific magnetic fields, showcasing versatile operational modes. (d,e) Spherical scaffolds MMRs for cell transportation. (f) MMRs made from PH-sensitive gel, enabling them to deform and adapt to different environmental conditions effectively. (g,h) The design of self-folding MMRs incorporates a folding mechanism that significantly accelerates their fabrication process. Figures adapted with permissions from ref. [60], Wiley, (a); ref. [40], Wiley, (b); ref. [42], ACS, (c); ref. [63], Wiley, (d); ref. [64], Wiley, (e); ref. [65], ACS, (f); ref. [66], Elsevier, (g); ref. [67] Wiley, (h).

Figure 4

Active drug release by external stimuli. (a) Stable cavitation induced by ultrasound facilitates the release of drugs, leveraging acoustic energy to enhance delivery efficiency. (b) The first drug GEM is released through near-infrared (NIR) induced disulfide bond cleavage, then the second drug DOX is released by MMR degradation, enabling controlled sequential delivery. (c) NIR promotes the hydrolysis of MMRs, thereby triggering drug release. (d) Changing magnetic fields unscrew the embolus of MMRs to facilitate targeted release. (e) The application of alternating magnetic fields (AMFs) heats the MNPs layer of bilayer robots, subsequently melting the temperature-sensitive, drug-loaded gel layer to release the drug. Figures adapted with permissions from ref. [60], Wiley, (a); ref. [56], ACS, (b); ref. [101], ACS, (c); ref. [39], Wiley, (d); ref. [49], Wiley, (e).

Figure 5

The design for degradation and retrieval of MMRs with biocompatibility consideration. (a–c) MMRs fabricated through biological templates and the adsorption and mixing method with MNPs, are, respectively, based on Chlamydomonas reinhardtii (Ch.), diatoms (TWF), and stem cells. These biological templates offer excellent biocompatibility and in vivo degradability. (d) NIR facilitates the degradation of MMRs, allowing for the retrieval of MNPs through a magnetic field. (e) NIR stimulation actively triggers the dissociation of MNPs from the robot’s surface through disulfide bond cleavage. Then MNPs can be retrieved by magnetic field. (f,g) Given the potential harm of MNPs to the human body, new MOF materials have been proposed. These materials boast superior biocompatibility and degradability in acidic solutions. Figures adapted with permissions from ref. [42], ACS, (a); ref. [104], Elsevier, (b); ref. [149], Wiley, (c); ref. [145], Elsevier, (d); ref. [48], ACS, (e); ref. [150], Wiley, (f); ref. [151], Wiley, (g).

Figure 1

The concept figure of this review. We systematically decouple recent works on MMRs for in vivo cargo delivery into a structured framework. The framework includes magnetic field actuation, structural design, cargo loading and release mechanisms, tracking, navigation, as well as the degradation and retrieval of MMRs.