Macrophage-Based Microrobots for Anticancer Therapy: Recent Progress and Future Perspectives

Macrophages, which are part of the mononuclear phagocytic system, possess sensory receptors that enable them to target cancer cells. In addition, they are able to engulf large amounts of particles through phagocytosis, suggesting a potential “Trojan horse” drug delivery approach to tumors by facilitating the engulfment of drug-hidden particles by macrophages. Recent research has focused on the development of macrophage-based microrobots for anticancer therapy, showing promising results and potential for clinical applications. In this review, we summarize the recent development of macrophage-based microrobot research for anticancer therapy. First, we discuss the types of macrophage cells used in the development of these microrobots, the common payloads they carry, and various targeting strategies utilized to guide the microrobots to cancer sites, such as biological, chemical, acoustic, and magnetic actuations. Subsequently, we analyze the applications of these microrobots in different cancer treatment modalities, including photothermal therapy, chemotherapy, immunotherapy, and various synergistic combination therapies. Finally, we present future outlooks for the development of macrophage-based microrobots

Four-Dimensional-Printed Microrobots and Their Applications: A Review

Owing to their small size, microrobots have many potential applications. In addition, four-dimensional (4D) printing facilitates reversible shape transformation over time or upon the application of stimuli. By combining the concept of microrobots and 4D printing, it may be possible to realize more sophisticated next-generation microrobot designs that can be actuated by applying various stimuli, and also demonstrates profound implications for various applications, including drug delivery, cells delivery, soft robotics, object release and others. Herein, recent advances in 4D-printed microrobots are reviewed, including strategies for facilitating shape transformations, diverse types of external stimuli, and medical and nonmedical applications of microrobots. Finally, to conclude the paper, the challenges and the prospects of 4D-printed microrobots are highlighted

Stable generation of multiple chemical gradients using in-situ formed nanoporous membranes

We developed a gradient generator of multiple chemicals using self-assembled particles in microchannels. The porous membranes based on the assembled particles allow the stable gradient generation without any convection flow disturbance and leakage. Moreover, they are more robust in dry environment and have long-term storage potential compared to hydrogel based membranes. Dynamic spatial control and the parallel preferential chemotaxis assay of salmonella typhimurium were successfully demonstrated. Our proposed devices are expected to be utilized for mimicking the real microenvironment for cells and various drug screening

Two distinct actin waves correlated with turns-and-runs of crawling microglia

© 2019 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Freely crawling cells are often viewed as randomly moving Brownian particles but they generally exhibit some directional persistence. This property is often related to their zigzag motile behaviors that can be described as a noisy but temporally structured sequence of “runs” and “turns.” However, its underlying biophysical mechanism is largely unexplored. Here, we carefully investigate the collective actin wave dynamics associated with the zigzag-crawling movements of microglia (as primary brain immune cells) employing a number of different quantitative imaging modalities including synthetic aperture microscopy and optical diffraction tomography, as well as conventional fluorescence imaging and scanning electron microscopy. Interestingly, we find that microglia exhibit two distinct types of actin waves working at two quite different time scales and locations, and they seem to serve different purposes. One type of actin waves is fast “peripheral ruffles” arising spontaneously with an oscillating period of about 6 seconds at some portion of the leading edge of crawling microglia, where the vigorously biased peripheral ruffles seem to set the direction of a new turn (in 2-D free space). When the cell turning events are inhibited with a physical confinement (in 1-D track), the peripheral ruffles still exist at the leading edge with no bias but showing phase coherence in the cell crawling direction. The other type is “dorsal actin waves” which also exhibits an oscillatory behavior but with a much longer period of around 2 minutes compared to the fast “peripheral ruffles”. Dorsal actin waves (whether the cell turning events are inhibited or not) initiate in the lamellipodium just behind the leading edge, travelling down toward the core region of the cell and disappear. Such dorsal wave propagations seem to be correlated with migration of the cell. Thus, we may view the dorsal actin waves are connected with the “run” stage of cell body, whereas the fast ruffles at the leading front are involved in the “turn” stag

Optimization of Field-Free Point Position, Gradient Field and Ferromagnetic Polymer Ratio for Enhanced Navigation of Magnetically Controlled Polymer-Based Microrobots in Blood Vessel

Microscale and nanoscale robots, frequently referred to as future cargo systems for targeted drug delivery, can effectively convert magnetic energy into locomotion. However, navigating and imaging them within a complex colloidal vascular system at a clinical scale is exigent. Hence, a more precise and enhanced hybrid control navigation and imaging system is necessary. Magnetic particle imaging (MPI) has been successfully applied to visualize the ensemble of superparamagnetic nanoparticles (MNPs) with high temporal sensitivity. MPI uses the concept of field-free point (FFP) mechanism in the principal magnetic field. The gradient magnetic field (|∇B|) of MPI scanners can generate sufficient magnetic force in MNPs; hence, it has been recently used to navigate nanosized particles and micron-sized swimmers. In this article, we present a simulation analysis of the optimized navigation of an ensemble of microsized polymer MNP-based drug carriers in blood vessels. Initially, an ideal two-dimensional FFP case is employed for the basic optimization of the FFP position to achieve efficient navigation. Thereafter, a nine-coil electromagnetic actuation simulation system is developed to generate and manipulate the FFP position and |∇B|. Under certain vessel and fluid conditions, the particle trajectories of different ferromagnetic polymer ratios and |∇B| were compared to optimize the FFP position

Concentration gradient generation of multiple chemicals using spatially controlled self-assembly of particles in microchannels

We present a robust microfluidic platform for the stable generation of multiple chemical gradients simultaneously using in situ self-assembly of particles in microchannels. This proposed device enables us to generate stable and reproducible diffusion-based gradients rapidly without convection flow: gradients are stabilized within 5 min and are maintained steady for several hours. Using this device, we demonstrate the dynamic position control of bacteria by introducing the sequential directional change of chemical gradients. Green Fluorescent Protein (GFP)-expressing bacterial cells, allowing quantitative monitoring, show not only tracking motion according to the directional control of chemical gradients, but also the gradual loss of sensitivity when exposed to the sequential attractants because of receptor saturation. In addition, the proposed system can be used to study the preferential chemotaxis assay of bacteria toward multiple chemical sources, since it is possible to produce multiple chemical gradients in the main chamber; aspartate induces the most preferential chemotaxis over galactose and ribose. The microfluidic device can be easily fabricated with a simple and cost effective process based on capillary pressure and evaporation for particle assembly. The assembled particles create uniform porous membranes in microchannels and its porosity can be easily controlled with different size particles. Moreover, the membrane is biocompatible and more robust than hydrogel-based porous membranes. The proposed system is expected to be a useful tool for the characterization of bacterial responses to various chemical sources, screening of bacterial cells, synthetic biology and understanding many cellular activities.close10

Acoustic Actuators for the Manipulation of Micro/Nanorobots: State-of-the-Art and Future Outlooks

Compared to other actuating methods, acoustic actuators offer the distinctive capability of the contactless manipulation of small objects, such as microscale and nanoscale robots. Furthermore, they have the ability to penetrate the skin, allowing for the trapping and manipulation of micro/nanorobots that carry therapeutic agents in diverse media. In this review, we summarize the current progress in using acoustic actuators for the manipulation of micro/nanorobots used in various biomedical applications. First, we introduce the actuating method of using acoustic waves to manipulate objects, including the principle of operation and different types of acoustic actuators that are usually employed. Then, applications involving manipulating different types of devices are reviewed, including bubble-based microrobots, bubble-free robots, biohybrid microrobots, and nanorobots. Finally, we discuss the challenges and future perspectives for the development of the field

Robotic Localization Based on Planar Cable Robot and Hall Sensor Array Applied to Magnetic Capsule Endoscope

Recently an active locomotive capsule endoscope (CE) for diagnosis and treatment in the digestive system has been widely studied. However, real-time localization to achieve precise feedback control and record suspicious positioning in the intestine is still challenging owing to the limitation of capsule size, relatively large diagnostic volume, and compatibility of other devices in clinical site. To address this issue, we present a novel robotic localization sensing methodology based on the kinematics of a planar cable driven parallel robot (CDPR) and measurements of the quasistatic magnetic field of a Hall effect sensor (HES) array. The arrangement of HES and the Levenberg-Marquardt (LM) algorithm are applied to estimate the position of the permanent magnet (PM) in the CE, and the planar CDPR is incorporated to follow the PM in the CE. By tracking control of the planar CDPR, the position of PM in any arbitrary position can be obtained through robot forward kinematics with respect to the global coordinates at the bedside. The experimental results show that the root mean square error (RMSE) for the estimated position value of PM was less than 1.13 mm in the X, Y, and Z directions and less than 1.14° in the θ and φ orientation, where the sensing space could be extended to ±70 mm for the given 34 × 34 mm2 HES array and the average moving distance in the Z-direction is 40 ± 2.42 mm. The proposed method of the robotic sensing with HES and CDPR may advance the sensing space expansion technology by utilizing the provided single sensor module of limited sensible volume

Polarity Control and Weak Fermi-Level Pinning in PdSe2 Transistors

Two-dimensional (2D) materials have been considered key materials for the future logic devices due to the excellent electrostatic integrity originating from their ultrathin nature. However, the carrier polarity control of 2D material field-effect transistors (FETs) still remains a challenging issue, hindering the realization of complementary logic function in the 2D material platform. Here, we report a comprehensive study on the electrical characteristics of PdSe2 FETs with different metal contacts. It is found that the carrier polarity in PdSe2 FETs can be modulated simply by changing the metal contact due to the weak Fermi-level pinning in PdSe2. We demonstrate a complementary metal-oxidesemiconductor (CMOS) inverter using the same channel material PdSe2, for n- and p-MOSFETs but with different metal contacts, suggesting the possible realization of PdSe2-based CMOS logic circuits