This study proposes a novel strategy for cross-scale position of robotic micromanipulation. The strategy utilizes multiple-scale augmented reality (AR) markers for locating the robotic manipulator on different scales. The macro-marker (3.0 cm-per side, 5 mm×5 mm each square) is applied to position the robot to the microscopic manipulation area. The micro-marker (2.4 mm-per side, 400 μm×400 μm each square) is used for positioning the end-effector under microscopic view. After the fabrication of the markers, the camera's internal parameter matrix was first calibrated. Subsequently, we conducted the detection effect of macro- and micro-markers. Since the observation effect of micro-markers is different under the microscope, the detection distance of the micro-marker was corrected and compensated, and the fixed reference marker was introduced for the correction in different focus heights. Finally, based on detection markers, a robotic manipulator, integrated with a microfluidic chip as an end-effector, was employed to demonstrate the micromanipulation of loading oocytes. The proposed strategy has a potential application in the biology laboratory automation.

This study proposes a novel movable microfluidic chip in which a microfluidic chip is integrated into a robotic manipulator for manipulating oocytes. The microfluidic device has the ability to release a single oocyte with a gap effect. The robotic manipulator can control the position of the microfluidic chip. The microfluidic chip with a pipette tip is directly fabricated using 3D printing. Xenopus oocyte was used in the experiment. When oocytes move from the back side of the channel to the front side, they generate gaps between each other. The gap distance can reach about 16 times the diameter of the oocyte. In addition, a capacitive sensor was used to detect oocytes in the manipulation processes. The results showed that oocytes were successfully released one by one with no deformation in shape using the movable microfluidic chip. The method has significant advantages in biomedicine engineering and micro-nano-manipulation.

Magnetic microrobots exhibit enormous potential in targeted drug delivery owing to the remote wireless manipulation and minimum invasion for medical treatment. High degree of freedom offers the magnetic propelled robots extraordinary application prospect since they can be controlled precisely when different magnetic fields sources working cooperatively. However, the biocompatibility of microrobots have attracted sustained and general concern. Therefore, it is highly necessary to develop a promising carrier with high biocompatibility and investigate the mechanism of drug loading-release triggered by special microenvironment in the targeted region. In this paper, we proposed a magnetically controlled cell robots (MCRs) based on macrophages propelled by a rotating magnetic field. The innovative MCRs exhibit good biocompatibility and low toxicity by optimizing the concentration of polylysine-coated Fe nanoparticles (PLL@FeNPs) to 40 µg/mL. These MCRs loaded with murine interleukin-12 (IL-12), murine chemokine (C-C motif) ligand 5 (CCL-5), and murine C-X-C motif chemokine ligand 10 (CXCL-10) which can stimulate T cell differentiation and recruitment of monocytes, respectively. The macrophages showed an obvious M1-polarization tendency of macrophages to phagocytose intracellular pathogens and resist the growth of tumor cells. Under the control of a magnetic propelling system composed of 3 pairs of Helmholtz coil, the cell robot can be propelled wirelessly and moved along a predefined path with high accuracy. Moreover, the MCRs could approach to cancer cells and stop at places of interest in vitro. In conclusion, we have accomplished the preliminary construction of a targeted drug delivery system which displays great immune-enhancing potential for targeted drug delivery.

In view of the magnetically actuated capsule robot applications in diagnoses of human stomach disease, the challenges that are associated with degrees-of-freedom (DOF), environmental adaptability, and the size of the entire system must be addressed. In this study, a new electromagnetic coil system that is based on adaptive magnetic levitation is presented; it is mainly composed of an independent orientation control electromagnetic coil and a magnetic levitation control electromagnetic coil. The system is designed to perform motion control of the capsule, including 3-DOF levitating translational motion control, and pitch and yaw motion control in levitation. In this manner, it compensates for the lack of previous magnetic levitation systems that were based on electromagnetic coils for the control of the tilt angle of the capsule. With torque-based actuation control, the tilt angle of the capsule can be controlled continuously with an angle increment of no more than 2° (within 30°) during levitation. The capsule under the magnetic levitation control, which is based on the fuzzy proportional-integral -derivative controller, can maintain the stability of levitation; the error between the actual capsule position and the required position did not exceed 0.1 mm when the capsule was out of water or completely immersed in it. Moreover, the experiment of the capsule levitating from air to water further verifies the adaptability of the system with regard to the environment; this provides a new examination method for capsule endoscopy. Note to Practitioners—This work is caused by the motion manipulation problem of a magnetically driven capsule robot. Most of the existing magnetically driven capsule robots use a rolling or sliding method that fits tightly against the stomach wall, and these forms of motion make it possible to risk missing diagnoses in the examination of gastric diseases, and the maneuverability limits its further application. This paper proposes an adaptive control strategy for a magnetically driven capsule robot based on magnetic levitation motion. It allows the magnetically driven capsule robot to levitate to any position in the stomach for photography and observation without external mechanical support, and this levitation motion is sufficiently stable. In addition, the proposed capsule robot has independent orientation and position control, which has the potential to achieve automated inspection.

Macrophage immunotherapy is a promising clinical approach to treat cancer. However, low targeting efficiency severely limits the immunotherapeutic effect of macrophages. Here, we report a unique macrophage robot that can target and kill cancer cells using a combination of external acoustic and magnetic fields. First, the inactive macrophages (Mø) are magnetized by endocytosis of the$\gamma$-Fe2O3nanoparticles (FeNPs). Then, the magnetized M⊘can be moved towards the capillary wall under the influence of an acoustic radiation force generated from a lead zirconate titanate piezoelectric (PZT) transducer. Finally, the magnetized cells rotate forward under the action of alternating magnetic fields (AMF). During the process of magnetizing macrophages, FeNPs activate the anti-tumor immune activity of macrophages (M1) to induce cancer cell death. Overall, the present study highlights a novel cell robot that can target and kill cancer cells. Considering that the nanoparticles, macrophages, magnetic fields, and ultrasound technology have all been FDA approved for clinical settings, our targeted delivery system has tremendous clinical translational potential.

Micro-nano-robots are considered to be a promising platform for drug delivery in biological organisms, but there are still urgent technical problems in biocompatibility and degradability of 3D-printed-based micro-robots that need to be solved. Therefore, in this paper, we design a magnetized bio-hybrid robot, which uses mouse macrophages as carriers, and allowed it to swallow Fe2O3particles with a diameter of 10 nm. The robot takes advantage of macrophage’s natural biocompatibility and targeting characteristics to reach and function in complex environments such as: eye, knee, tumor, etc., and finally being able to be actively metabolized by the organism. More importantly, the cell robot can move precisely along a preplanned path under the control of a three-dimensional magnetic control system built in this study, and be delivered accurately to the vicinity of cancer cells in vitro environment. In future work, cellular robots could be allowed to carry anti-cancer drugs and release them in a targeted manner at the lesion. These microrobots have shown great potential for tumor reginal targeted drug delivery.

Circulating tumor cells (CTCs) are the primary cause of tumor metastasis after surgery. Metastatic tumor recurrence is the leading reason of cancer death. It is prerequisite to develop a platform for CTCs separation to predict the cancer cell transfer in important organs. Herein, a novel acoustic microfluidic device was designed to capture the "true" CTCs from the whole blood sample. The blood got from the mice with breast tumors removed. There are some CTCs that have escaped from the solid tumor contained in these blood samples, instead of artificially mixing individual tumor cells into normal blood. In addition, the predictions of tumor prognosis are made based on the number of CTCs captured by the acoustofluidic device. Finally, the prediction has been confirmed through long-term observation of mice with tumor excised. The acoustofluidic device can efficiently capture CTCs and predict the tumor metastasis, which can help clinicians plan follow-up treatment for patients who have had their tumors surgically removed.

In this paper, we present a magnetized cell-robot using macrophages as templates, which can be controlled under a strong gradient magnetic field, to approach and kill cancer cells in both vitro and vivo environment. Firstly, we establish a magnetic control system using only four coils which can generate gradient field up to 4.14 T/m utilizing the coupled field contributed by multiple electromagnets acting in concert. Most importantly, the cell-robot which is based on the macrophage is proposed, and can be transported to the vicinity of cancer cells precisely using strong gradient magnetic field. Then the cell-robot will actively phagocytose the cancer cells and eventually kill them, achieving the cancer treatment at the cellular level. It has important significance for guiding accurate targeted therapy in vivo for the future, under the premise of zero harm to the human body.

Magnetic microrobots can be propelled precisely and wirelessly in vivo using magnetic field for targeted drug delivery and early detection. They are promising for clinical trials since magnetic fields are capable of penetrating most materials with minimal interaction, and are nearly harmless to human beings. However, challenges like the biocompatibility, biodegradation and therapeutic effects of these robots must be resolved before this technique is allowed for preclinical development. In this study, we proposed a cell-robot based on macrophages for carrying drugs to kill tumors propelled by magnetic gradient-based pulling. A custom-designed system with strong gradient magnetic field system in three-dimensional (3D) space using the minimum number of coils is used for precise control of the cell-based microrobot. The cell-based microrobots were fabricated by assembling magnetic nanoparticles (Fe3O4), anti-cancer drugs (DOX) into macrophages for magnetic actuation and therapeutic effects. Vitro experiments show that cell-based microrobots can be accurately transported to the destination or approaching a targeted cancer cell. The magnetic nanoparticles have negligible effects on the cell-based microrobot and the organism, which makes the cell-based microrobot safe for in vivo experiments. The carried drugs in the cell-based microrobot can be released by the irradiation of the near-field infrared and kill the cancer cells. Further in vivo experiments prove that the cell-based microrobot can be transported to tumor area and release drugs to kill cancer effectively. The research provides biocompatible and biodegradable cell-based microrobots for early tumor prevention and targeted precision therapy.