Investigation of in vivo Navigation of Microrobots Actuated by a Magnetic Gradient Field-Based Manipulation System under in vivo Imaging Feedback


Student thesis: Doctoral Thesis

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Award date29 Aug 2019


The precise delivery of targeted cells/drugs through magnetically-driven microrobots represents a promising technique for targeted therapy and tissue regeneration. Electromagnetic-based actuation and in vivo imaging technology have received increasing attention over the past decades to manipulate the microrobots. However, the previous electromagnetic manipulation system may not fulfill the requirements of the in vivo manipulation because of insufficient actuation force. The in vivo imaging technologies, which have been used in previous works, cannot detect the microrobot with a size of less than 100 μm in deep tissue in real time. In this study, we introduce an electromagnetic manipulation system with a new core shape design and two in vivo imaging technologies for the in vivo studies. This research is conducted on the basis of the following three aspects:

First, a magnetic gradient field-based actuation system adopting a new core shape design is utilized. The iron core shape and probe size are optimized on the basis of mathematical modeling to increase the magnetic field gradient. The performance evaluation of the developed electromagnetic manipulation system exhibits the correction of the theoretical part. The designed system is tested in different in vitro environments and in an in vivo one, namely, zebrafish yolk. Experimental results effectively demonstrate the capacity of the designed platform in manipulating microrobots for in vitro and in vivo applications.

Second, a study on the in vivo navigation of microrobots is performed by using optical coherence tomography (OCT) imaging feedback. The electromagnetic gradient field generated by the electromagnetic manipulation system is modeled. The magnetic force acting on the microrobot is calculated, and the relationship between this force and the velocity of the microrobot is characterized. The findings are verified by the in vitro experiments in three types of fluid with the help of the OCT imaging system. In vivo experiments are then performed to navigate the microrobot cultured with stem cells in mouse portal veins. The microrobot is navigated in the portal veins under the actuation of the electromagnetic manipulation system and the tracking of the OCT imaging system, under a tissue thickness of 2 mm and steadily moves 3 mm.

Third, a photoacoustic (PA) imaging system is also employed to navigate the microrobots. Employing the 800 nm pulsed laser, PA imaging has the deep imaging depth advantage, which can help navigate the microrobots in deep tissues. Microrobots are detected in tissues with different thicknesses to verify this feature. The PA signal can be further enhanced through coating gold onto the microrobots and adjusting the wavelength of the pulse laser. Optimization of the optical path greatly decrease the risk of the tissue damage caused by the pulsed laser. The microrobot cluster carrying functional steam cells is injected into the mouse portal veins and navigated by the electromagnetic manipulation system with the help of PA imaging. Experimental results show that PA imaging is a practical technique for navigating microrobots in vivo.

In summary, this study has demonstrated that the developed electromagnetic manipulation system and employed in vivo imaging technology can be effectively utilized to manipulate and track the microrobot, especially for the in vivo application. This work represents a significant progress for the manipulation and real-time positioning of the cell cultured microrobots in vivo. The success of this study will constitute a technological platform for cell-based therapy and tissue regeneration for precise medicine in the future.