Medical microrobots in reproductive medicine from the bench to the clinic.

Medical microrobotics is an emerging field that aims at non-invasive diagnosis and therapy inside the human body through miniaturized sensors and actuators. Such microrobots can be tethered (e.g., smart microcatheters, microendoscopes) or untethered (e.g., cell-based drug delivery systems). Active motion and multiple functionalities, distinguishing microrobots from mere passive carriers and conventional nanomedicines, can be achieved through external control with physical fields such as magnetism or ultrasound. Here we give an overview of the key challenges in the field of assisted reproduction and how these new technologies could, in the future, enable assisted fertilization in vivo and enhance embryo implantation. As a case study, we describe a potential intervention in the case of recurrent embryo implantation failure, which involves the non-invasive delivery of an early embryo back to the fertilization site using magnetically-controlled microrobots. As the embryo will be in contact with the secretory oviduct fluid, it can develop under natural conditions and in synchrony with the endometrium preparation. We discuss the potential microrobot designs, including a proper selection of materials and processes, envisioning their translation from bench to animal studies and human medicine. Finally, we highlight regulatory and ethical considerations for bringing this technology to the clinic.

Magnetic soft micromachines made of linked microactuator networks.

Soft untethered micromachines with overall sizes less than 100 µm enable diverse programmed shape transformations and functions for future biomedical and organ-on-a-chip applications. However, fabrication of such machines has been hampered by the lack of control of microactuator's programmability. To address such challenge, we use two-photon polymerization to selectively link Janus microparticle-based magnetic microactuators by three-dimensional (3D) printing of soft or rigid polymer microstructures or links. Sequentially, we position each microactuator at a desired location by surface rolling and rotation to a desired position and orientation by applying magnetic field-based torques, and then 3D printing soft or rigid links to connect with other temporarily fixed microactuators. The linked 2D microactuator networks exhibit programmed 2D and 3D shape transformations, and untethered limbless and limbed micromachine prototypes exhibit various robotic gaits for surface locomotion. The fabrication strategy presented here can enable soft micromachine designs and applications at the cellular scales.