Microswimmers That Flex: Advancing Microswimmers with Templated Assembly and Responsive DNA Nanostructures

The concept of micrometer-scale swimming robots, also known as microswimmers, navigating the human body to perform robotic tasks has captured the public imagination and inspired researchers through its numerous representations in popular media. This attention highlights the enormous interest in and potential of this technology for biomedical applications, such as cargo delivery, diagnostics, and minimally invasive surgery, as well as for applications in microfluidics and manufacturing. To achieve the collective behavior and control required for microswimmers to effectively perform such actions within complex, in vivo and microfluidic environments, they must meet a strict set of engineering criteria. These requirements include, but are not limited to, small size, structural monodispersity, flexibility, biocompatibility, and multifunctionality. Additionally, microswimmers must be able to adapt to delicate environments, such as human vasculature, while safely performing preprogrammed tasks in response to chemical and mechanical signals. Naturally information-bearing biopolymers, such as peptides, RNA, and DNA, can provide programmability, multifunctionality, and nanometer-scale precision for manufactured structures. In particular, DNA is a useful engineering material because of its predictable and well-characterized material properties, as well as its biocompatibility. Moreover, recent advances in DNA nanotechnology have enabled unprecedented abilities to engineer DNA nanostructures with tunable mechanics and responsiveness at nano- and micrometer scales. Incorporating DNA nanostructures as subcomponents in microswimmer systems can grant these structures enhanced deformability, reconfigurability, and responsiveness to biochemical signals while maintaining their biocompatibility, providing a versatile pathway for building programmable, multifunctional micro- and nanoscale machines with robotic capabilities. In this Account, we highlight our recent progress toward the experimental realization of responsive microswimmers made with compliant DNA components. We present a hybrid top-down, bottom-up fabrication method that combines templated assembly with structural DNA nanotechnology to address the manufacturing limitations of flexibly linked microswimmers. Using this method, we construct microswimmers with enhanced structural complexity and more controlled particle placement, spacing, and size, while maintaining the compliance of their DNA linkage. We also present a novel experimental platform that utilizes two-photon polymerization (TPP) to fabricate millimeter-scale swimmers (milliswimmers) with fully customizable shapes and integrated flexible linkers. This platform addresses limitations related to population-level heterogeneity in micrometer-scale systems, allowing us to isolate the effects of milliswimmer designs from variations in their physical dimensions. Using this platform, we interrogate established hydrodynamic models of microswimmer locomotion and explore how design and actuation parameters influence milliswimmer velocity. We next explore opportunities for enhancing microswimmer responsiveness, functionality, and physical intelligence through the inclusion of nucleic acid subcomponents. Finally, we highlight how our parallel research on xeno nucleic acids and interfacing DNA nanotechnology with living cells can enable the creation of fully organic, truly biocompatible microswimmers with enhanced functionality, improving the viability of microswimmers for applications in healthcare, manufacturing, and synthetic biology.