The clinical efficacy of many conventional passive drug delivery systems is frequently constrained by their low targeting efficiency, important off-target toxicity, and inadequate capacity for traversing biological barriers. Autonomous microrobots, as miniature intelligent platforms capable of active navigation and on-demand responsiveness, offer an active delivery strategy for achieving spatiotemporally precise targeted therapy. This review aims to systematically consolidate and critique the theoretical foundations, key technologies, cutting-edge applications, and future challenges of this emergent interdisciplinary field. We first provide an in-depth analysis of the technological frameworks underpinning the 2 core functionalities: targeted delivery and on-demand release. This encompasses a diverse array of propulsion and navigation strategies—from chemical and physical fields to biohybrid systems—as well as programmed drug release mechanisms responsive to endogenous and exogenous stimuli. Building on this, we introduce a hierarchical paradigm organized by biological-barrier traversal capability to review the preclinical progress of microrobots, from localized delivery in accessible body cavities to deep-tissue and trans-barrier applications. This function-oriented framework more directly links microrobot design to the progressive physiological constraints encountered in vivo, thereby providing a more integrated and translationally relevant perspective on biomedical applications and clinical potential. Concurrently, this paper examines the bottlenecks impeding their clinical translation, including biosafety, systemic controllability, and regulatory science. Looking forward, the deep integration of microrobotics with smart materials, artificial intelligence, and theranostic systems is poised to cultivate a new generation of intelligent medical robots capable of personalized treatment via closed-loop manners.

Magnetic miniature robots have shown great potential in biomedical applications in recent years. However, a challenge remains in which it is difficult for magnetic miniature robots to achieve balanced capabilities for multimodal locomotion and fluidic manipulation in various environments. Here, we report a magnetic shaftless propeller-like millirobot (MSPM) that possesses the capabilities of rotating-based multimodal 3-dimensional motion and cargo transportation with untethered manipulation. The MSPM utilizes the propulsion and pumping capabilities of the propeller structure to achieve fluidic manipulation. The shaftless propeller structures are designed to achieve omnidirectional locomotion through rolling, propelling, and tumbling. Additionally, the shaftless 3-blade propeller is used to perform a pumping function to achieve controllable transportation of fluids and particles. We anticipate that the MSPM holds great potential as a minimally invasive device for thrombosis treatment and targeted medicine delivery.

Digital microfluidic chips (DMCs) have shown huge potential for biochemical analysis applications due to their excellent droplet manipulation capabilities. The driving force is a critical factor for characterizing and optimizing the performance of droplet manipulation. Conducting numerical analysis of the driving force is essential for DMC design, as it helps optimize the structural parameters. Despite advances in numerical analysis, evaluating driving forces in partially filled electrodes remains challenging. Here, we propose a versatile electrodynamics simulation model designed to analyze the driving forces of partially filled electrodes to optimize the structural parameters of DMCs. This model utilizes finite element analysis to determine the voltage distribution within the DMC and calculates the driving force acting on the droplets using the principles of virtual work. Using this electrodynamics simulation model, we evaluated the effects of various structural parameters, including the dielectric constant and thickness of the dielectric layer, the dielectric constant and conductivity of the droplet, and substrate spacing, on the droplet driving force. This evaluation helps to optimize the structural parameters and enhances the droplet manipulation of DMCs. Measurements of droplet acceleration demonstrated that the droplet acceleration on the partially filled electrode aligns with the simulated driving force trend, which verified the effectiveness of the proposed electrodynamics simulation model. We anticipate that the electrodynamics simulation model is capable of evaluating the driving force in partially filled electrodes within complex DMCs, offering unprecedented possibilities for future structural designs of DMCs.

Microfluidic chips offer high customizability and excellent biocompatibility, holding important promise for the precise control of biological growth at the microscale. However, the microfluidic chips employed in the studies of regulating cell growth are typically fabricated through 2D photolithography. This approach partially restricts the diversity of cell growth platform designs and manufacturing efficiency. This paper presents a method for designing and manufacturing neural cell culture microfluidic chips (NCMC) using two-photon polymerization (TPP), where the discrete and directional cell growth is optimized through studying the associated geometric parameters of on-chip microchannels. This study involves simulations and discussions regarding the effects of different hatching distances on the mold surface topography and printing time in the Describe print preview module, which determines the appropriate printing accuracy corresponding to the desired mold structure. With the assistance of the 3D maskless lithography system, micron-level rapid printing of target molds with different dimensions were achieved. For NCMC with different geometric parameters, COMSOL software was used to simulate the local flow velocity and shear stress characteristics within the microchannels. SH-SY5Y cells were selected for directional differentiation experiments on NCMC with different geometric parameters. The results demonstrate that the TPP-based manufacturing method efficiently constructs neural microfluidic chips with high precision, optimizing the discrete and directional cell growth. We anticipate that our method for designing and manufacturing NCMC will hold great promise in construction and application of microscale 3D drug models.

Flexible miniature robots are expected to enter difficult-to-reach areas in vivo to carry out targeted operations, attracting widespread attention. However, it is challenging for the existing soft miniature robots to substantially alter their stable shape once the structure is designed. This limitation leads to a fixed motion mode, which subsequently restricts their operating environment. In this study, we designed a biocompatible flexible miniature robot with a variable stable form that is capable of adapting to complex terrain environments through multiple movement modes. Inspired by the reversible stretching reaction of alginate saline gel stimulated by changes in environmental ion concentration, we manufactured a morphologically changeable super-soft hydrogel miniature robot body. According to the stretch and contraction shapes of the flexible hydrogel miniature robot, we designed magnetic fields for swing and rolling motion modes to realize multi-shape movement. The experimental results demonstrate that the deflection angle of the designed flexible miniature robot is reversible and can reach a maximum of 180°. The flexible miniature robot can complete forward swinging in the bar stretch state and tumbling motion in the spherical state. We anticipate that flexible hydrogel miniature robots with multiple morphologies and multimodal motion have great potential for biomedical applications in complex, unstructured, and enclosed living environments.