Existing approaches for robotic control of magnetic swarms are not capable of generating magnetic aggregates precisely in an arbitrarily specified target region in a fluidic flow environment. Such a swarm control capability is demanded by medical applications such as clinical embolization (i.e., localized clogging of blood vessels). This paper presents a new magnetic swarm control strategy to generate aggregates only in a specified target region under fluidic flow. Within the target region, the magnetic field generates sufficiently large magnetic forces among magnetic particles to maintain the aggregates' integrity at the junctions of blood vessels. In contrast, unintended aggregates outside the target region are disassembled by fluidic shear. The aggregation control approach achieved a mean absolute error of 0.15 mm in positioning a target region and a mean absolute error of 0.30 mm in controlling the target region's radius. With thrombin coating, 1 μm magnetic particles were controlled to perform embolization both in vitro (using microfluidic channel networks) and ex vivo (using porcine tissue). Experiments proved the effectiveness of the swarm control technique for on-demand, targeted embolization.

Magnetic micromanipulation is an untethered technique and has enabled numerous applications in the scale of millimeters to micrometers from the tissue level to cell level. However, existing systems are not capable of maneuvering a sub-micrometer object for precise force control, preventing the realization of intracellular manipulation or `fantastic voyage' inside a single cell. The magnetic micromanipulation task achieved in this work is sub-micrometer position control and piconewton force control of a sub-micron (0.7 μm) magnetic bead inside a single human bladder cancer cell (RT4). The magnetic bead was 3D positioned in the cell using a generalized predictive controller that effectively tackled the control challenge caused by the slow visual feedback (1 Hz) from high-resolution confocal microscopy. The average positioning error was quantified to be 0.43 μm, which is slightly larger than Brownian motion-imposed constraint (0.31 μm). The system is capable of three-dimensionally applying a maximum force of 60 pN with a resolution of 4 pN. In experiments, a 0.7 μm magnetic bead was controlled to move from an initial position in a cell to target positions on the cell nucleus. Force-displacement data were obtained from multiple locations along the cell nucleus' major and minor axes. The results revealed, for the first time, significantly higher stiffness exists in the cell nucleus' major axis than the minor axis. This stiffness polarity was likely attributed to the aligned stress fibers of actin filament inside the cells.

Magnetic micromanipulation has the advantage of untethered control, high precision, and biocompatibility and has recently undergone great advances. The magnetic micromanipulation task to tackle in this paper is to three dimensionally navigate a 5-μm magnetic bead inside a mouse embryo and accurately apply forces to intraembryonic structures to perform mechanical measurements at multiple locations. Existing technologies are not able to achieve these navigation and measurement goals because of poor magnetic force scaling and/or lacking the capability of applying an accurately controlled force. This paper reports a three-dimensional magnetic tweezer system that enables, for the first time, intraembryonic magnetic navigation and force application. A single magnetic bead was introduced into a mouse embryo via robotic microinjection. The magnetic tweezer system accurately controlled the position of the magnetic bead via visually servoed magnetic control. By moving the magnetic bead with known forces inside the embryo, cytoplasm viscosity was measured, which is eight times the viscosity of water. For performing mechanical measurements on the cellular structures inside the mouse embryo, the system should be capable of applying forces up to 120 pN with a resolution of 4 pN. The results revealed that the middle region is significantly more deformable than the side regions of the inner cell mass.

Magnetic micromanipulation has the advantage of untethered control, high precision, and biocompatibility and has recently undergone great advances. The magnetic micromanipulation task to tackle in this work is to three-dimensionally navigate a 5-micrometer magnetic bead inside a mouse embryo and perform mechanical measurements at multiple locations. Existing technologies are not able to achieve these navigation and measurement goals because of poor magnetic force scaling and/or lacking the capability of applying an accurately controlled force. This paper reports a robotic magnetic tweezer system that enables, for the first time, intra- embryonic magnetic navigation and force application. A single magnetic bead was introduced into a mouse embryo via robotic microinjection. The robotic magnetic tweezer system accurately controls the position of the magnetic bead via visually servoed magnetic control. The system is also capable of applying forces up to 120 pN with a resolution of 1.78 pN for performing mechanical measurements on the cellular structures inside the mouse embryo, revealing that the middle region is more deformable than the side regions of the inner cell mass.