Targeted drug delivery technology using untethered microrobots: a review

Abstract

Targeted drug delivery is a promising application of microrobots owing to the capability of the microrobots to access nearly every region of the human body through the circulatory system. Research on microrobots over the past few decades has enabled substantial advances in the design of both the untethered microrobots swimming in a biofluid and the related mechanisms to carry and release therapeutic agents in a controlled manner. This paper presents a comprehensive review of the technological state of the art in untethered microrobots for targeted drug delivery applications. First, the in vivo microrobot locomotion techniques are discussed with respect of the different types of actuation energy sources such as magnetic fields, motile microorganisms, acoustic waves, and chemical reaction, outlining the respective advantages and major limitations. Subsequently, recent progress in various technologies of microrobot-driven targeted drug delivery is surveyed deliberating on the corresponding drug manipulation mechanisms: magnetically driven, motile microorganisms-driven, acoustic-aided, and stimuli-responsive hydrogels-aided. Although most studies on microrobot-driven targeted drug delivery were carried out in vitro, few among them successfully demonstrated in vivo operations in living animals. In the concluding section, current challenges and future perspectives of the microrobot-driven targeted drug delivery technology are discussed.

Perspective: Ferromagnetic Liquids

“…In this sense, ferromagnetic liquids open up an entirely new world of magnetic materials benefiting from mechanical and magnetic reconfigurability; for instance, 3D printed water-in-oil magnetic liquid tubules offer arbitrary shape (fluidity) and self-adaptive permanent magnetization (solidity), which benefit magnetic liquid actuators, non-contact liquid capsule delivery and other magnetically controlled devices in all-liquid environment. Magnetically driven autonomous technology often relates to the parallelized and sequential operations with respect to actuators in medical diagnostics, non-contact delivery and chemicals synthesis [56][57][58][59][60][61][62][63]. Reconfigurable ferromagnetic liquids representing magnetic liquid actuators and sensors, interact with the external magnetic field to exert translation and precession movement that can be facilitated in analogy to solid-state magnets.…”

“…The overarching questions regarding magnetic sensing with ferromagnetic liquids is the detection of physical changes that is conveniently done by magneto-resistance measurements in exchange-coupled metallic materials. For these applications, electro-chemical plating using a porous alumina template and strain-engineering rolled-up nanotech facilitating intrinsic strain gradients have been employed [60,61] and refined to synthesize nano-rods, nano-tubes and multi-segmented specimens [64][65][66][67][68][69][70] with variable diameter (<50 nm), and microtubules with tailored magnetization configuration [71,72] that achieve unprecedented sensitivity based on the giant magneto-impedance effect [73].…”

Magnetic Micromachine Using Nickel Nanoparticles for Propelling and Releasing in Indirect Assembly of Cell-Laden Micromodules

“…As shown in Figure 1a, a multi-layer mold was designed to improve precision and repeatability. The stainless steel template had high stiffness and ccould be reused without wear, compared with conventional PDMS or SU-8 soft-lithography [29,30]. Chemical etching is a common method to pattern stainless steel with high-resolution, which determines the shape and height of micromachines [31].…”

Sperm Cell Driven Microrobots—Emerging Opportunities and Challenges for Biologically Inspired Robotic Design

“…(iv) Drug carrying capability-Ultimately, the spermbot should be able to do what it is intended for-carry and deliver the drug to the targeted site. Various applications of sperm driven micro-bio-robots in the field of biomedical research areas are emerging that aim at achieving locomotion on the microscale such as drug delivery and single cell manipulation [31,[52][53][54][55] (Figure 2). Taking cue from this impressive structure, there has been considerable interest in developing artificial structures mimicking the motion of these flagella using external magnetic fields [20,25,56].…”