Publications

Wireless trackers have emerged as a crucial technology in minimally invasive medical procedures with their remote localization capabilities. Existing trackers suffer from miniaturization issues and complex designs, which limit their integration into medical devices. We present nuclear magnetic resonance (NMR) magnetic sensing, a quantum sensing approach with nT sensitivity for wireless magnetic tracking. NMR magnetic sensing enables millimeter-scale tracking accuracy and versatile miniaturized tracker designs for minimally invasive medical devices in magnetic resonance imaging scanners. As examples, we demonstrate miniature magnetic trackers with submillimeter-scale diameters for guidewires and optic fibers, flexible magnetic trackers for soft devices, and ferrofluidic trackers for shape-morphing devices. With the demonstrated miniaturization and wide range of tracker design possibilities, wireless magnetic tracking with NMR is promising for future minimally invasive medical operations.

Precision drug delivery remains a significant challenge due to limitations in drug loading, targeted release, precise navigation, and real-time monitoring. Here, the study reports a magnetic microrobot platform (MMP) that integrates high-capacity drug loading, magnetically actuated collective navigation, controlled drug release, and real-time 3D optoacoustic imaging in a single system. The MMP exploits synergistic advantages by embedding hard-magnetic FePt nanoparticles in a degradable ZIF-8 shell, achieving a drug loading efficiency of ≈93.9% and enabling precise release in response to pH changes and radiofrequency-induced heating. Reconfigurable swarm behavior strategies significantly enhance the navigation efficiency of microrobots against physiological blood flows within complex cerebral vasculature. The ex vivo and in vivo experiments further demonstrate strong contrast characteristics of the microrobots, enabling high-resolution visualization of deep vascular structures and dynamic tracking of MMP with real-time 3D optoacoustic imaging. This multifunctional strategy paves the way for clinical translation and precision therapy in complex biological settings.

Giant unilamellar vesicles (GUVs), soft cell-sized compartments formed through the self-assembly of lipid molecules, have long been utilized as model systems and passive carriers in membrane biophysics and biomedical applications. However, their potential as dynamically responsive and motile systems remains largely untapped due to challenges in achieving controlled and sustained motion in soft, deformable structures. Here, an autonomous cell-like microrobot through the emergent self-assembly of GUVs (5-10 µm) and silica microparticles (1-3 µm) under alternating current electric fields is realized. Self-propulsion arises from asymmetric self-organization of the particles on the vesicle surface, enabling a reversible transformation of the assembly into an active structure. Unlike rigid colloidal systems, GUVs introduce unique features enabled by their soft lipid membranes: shape deformations, membrane tension-dependent motility, and field-triggered live bacteria release via vesicle bursting. Through experiments and simulations, the mechanisms underlying self-assembly and propulsion are investigated, and a dynamic phase diagram is constructed to map the motion regime as a function of field parameters. Finally, it is shown that these self-assembled structures are capable of reconfiguration in response to local constraints in the environment, suggesting potential applications in complex environments and advancing the potential of GUVs toward the rational design of cell-like microrobots or artificial cell systems.

Wireless neural interfaces are emerging as a minimally invasive treatment option for neurological disorders. Among the wireless technologies, magnetically powered systems are effective for targeting deep brain sites. However, dependence on high-frequency electromagnetic fields in such systems limits their safe implementation. In this study, we demonstrate the use of millimeter-scale magnetoelectric (ME) films as a direct neural interface for wireless neurostimulation, powered by static and alternating magnetic fields in the nonresonant regime (10 hertz). To accomplish this objective, electrical potential trends of the ME films under varying low-frequency magnetic fields are investigated and used to demonstrate neural stimulation by calcium imaging on primary neurons in vitro via a capacitive-like charge injection mechanism. In addition, electrical polarization orientation is revealed as a critical design parameter in direct neuron-ME interfaces. These findings collectively demonstrate the potential of nonresonant powering of ME films as a promising minimally invasive wireless neural stimulation technique.

Covalent organic frameworks (COFs) have been emerging as versatile reticular materials due to their tunable structures and functionalities, enabled by precise molecular engineering at the atomic level. While the integration of multiple components into COFs has substantially expanded their structural complexity, the strategic engineering of diverse functionalities within a single framework via the random distribution of linkers with varying lengths remains largely unexplored. Here, we report a series of highly crystalline mixed-length multivariate COFs synthesized using azobenzene and bipyridine as linkers, where tuning the ratio of linkers and incorporating palladium effectively modulates the balance between near-infrared (NIR) light absorption and catalytic sites for NIR-generation of hydrogen peroxide (H2O2). Capitalizing on the deep tissue penetration of NIR light and the generated H2O2 as reactive oxygen species, as a proof of concept, the optimal mixed-length multivariate COF reduces breast cancer cell viability by almost 90% after 1 h of irradiation in a combined in vitro photodynamic therapy and drug delivery.

Magnetic soft robots offer considerable potential across various scenarios, such as biomedical applications and industrial tasks, because of their shape programmability and reconfigurability, safe interaction and biocompatibility1,2,3,4. Despite recent advances, magnetic soft robots are still limited by the difficulties in reprogramming their required magnetization profiles in real time on the spot (in situ), which is essential for performing multiple functions or executing diverse tasks5,6. Here we introduce a method for real-time in situ magnetization reprogramming that enables the rearrangement and recombination of magnetic units to achieve diverse magnetization profiles. We explore the applications of this method in structures of varying dimensions, from one-dimensional tubes to three-dimensional frameworks, showcasing a diverse and expanded range of configurations and their deformations. This method also demonstrates versatility in diverse scenarios, including navigating around objects without undesired contact, reprogramming cilia arrays, managing multiple instruments cooperatively or independently under the same magnetic field, and manipulating objects of various shapes. These abilities extend the range of applications for magnetic actuation technologies. Furthermore, this method frees magnetic soft robots from the sole reliance on external magnetic fields for shape change, facilitating unprecedented modes and varieties of deformation while simultaneously reducing the need for complex magnetic field generation systems, thereby opening avenues for the development of magnetic actuation technologies.

Bacterial biohybrid microrobots possess significant potential for targeted cargo delivery and minimally invasive therapy. However, many challenges, such as biocompatibility, stability, and effective cargo loading, remain. Bacterial membrane vesicles, also referred to as minicells, offer a promising alternative for creating sub-micron scale biohybrid swimmers (minicell biohybrids) due to their active metabolism, non-dividing nature, robust structure, and high cargo-carrying capacity. Here, a biohybrid system is reported that utilizes motile minicells, ≈400 nm in diameter, generated by aberrant cell division of engineered Escherichia coli (E. coli), for the first time. Achieving over 99% purification from their parental bacterial cells, minicells are functionalized with magnetic nanoparticles (MNPs) to enable external magnetic control. Minicell biohybrids are capable of swimming at an average speed of up to 13.3 µm s−1 and being steered under a uniform magnetic field of 26 mT. Furthermore, they exhibit a significantly high drug loading capacity (2.8 µg mL−1) while maintaining their motility and show pH-sensitive release of anticancer drug doxorubicin hydrochloride (DOX) under acidic conditions. Additionally, drug-loaded minicell biohybrids notably reduce the viability of SK-BR-3 breast cancer cells in vitro. This study introduces minicell biohybrids and establishes their potential as magnetically guided, drug-loaded biohybrid systems for targeted therapies in future medical applications.

Intraocular drug implants are increasingly used for retinal treatments, such as age-related macular degeneration and diabetic macular edema, due to the rapidly aging global population. Although these therapies show promise in arresting disease progression and improving vision, intraocular implant-based therapies can cause unexpected complications that require further surgery due to implant dislocation or uncontrolled drug release. These frequent complications of intraocular drug implants can be overcome using magnetically controllable degradable milliscale swimmers (MDMS) with a double-helix body morphology. A biodegradable hydrogel, polyethylene glycol diacrylate, is employed as the primary 3D printing material of MDMS, and it is magnetized by decorating it with biocompatible polydopamine-encapsulated iron-platinum nanoparticles. MDMS have comparable dimensions to commercial intraocular implants that achieve translational motions in both aqueous and vitreous bodies. They can be imaged in real-time using optical coherence tomography, ultrasound, and photoacoustic imaging. Thanks to their biodegradable hydrogel-based structure, they can be loaded with anti-inflammatory drug molecules and release the medications without disrupting retinal epithelial viability and barrier function, and decrease proinflammatory cytokine release significantly. These magnetically controllable swimmers, which degrade in a couple of months, can be used for less invasive and more precise intraocular drug delivery compared to commercial intraocular drug implants.

Synthetic microrobots have gained significant attention due to their potential in various applications in biomedicine and lab-on-a-chip technologies. As a fundamental requirement, microrobots must navigate in 3D, effectively counteracting gravity to execute their tasks. However, locomotion at small scales presents numerous counterintuitive behaviors, primarily governed by the interactions between the microrobot's body and its surrounding boundaries. In this study, the locomotion of surface-rolling microrobots is investigated in 3D, particularly focusing on their ability to climb walls. Through a combination of experiments and computational fluid dynamics analyzes, it is demonstrated that the influence of gravity plays a secondary role in enabling surface-rolling microrobots to climb walls. Instead, locomotion capability in 3D settings is primarily determined by interactions with surrounding boundaries. The fundamental principles of surface-rolling locomotion in 3D spaces is elucidated and a design strategy aimed at optimizing fluid flow for efficient propulsion in future applications is proposed.

Magnetic surface microrollers have demonstrated promise as active drug delivery agents for targeted and minimally invasive disease treatment. Specifically, it can be employed in the circulatory system to locally release therapeutic agents at disease sites, minimizing systemic exposure and reducing side effects, particularly in the treatment of diseases like cancer. Previous research indicates that the design and shape of microrollers play a crucial role in safe navigation within blood vessels, with anisotropic microrollers exhibiting superiority due to favorable hydrodynamic interactions with nearby boundaries. In this study, the navigation potential of anisotropic microrollers is investigated in veins, venules, and capillaries through computational fluid dynamics analyses. These results indicate that robust locomotion is only achievable in larger vessels, such as veins. Subsequently, their performance is explored in a clinically relevant scenario – the hepatic circulation toward treating primary liver cancer or metastatic nodes of distant tumors (e.g., pancreatic cancer). Computational fluid dynamics analyses using the data from five different patients demonstrate that robust navigation can be achieved with high actuation frequencies. Overall, the findings presented in this study lay a preliminary foundation for the potential future application of surface microrollers in vivo.

In the natural world, microorganisms constantly navigate through confined spaces—such as those found in tissues, biological gels, and soil—yet their behavior in such environments remains poorly understood. Here, we explore this phenomenon by examining the navigation of magnetic microalgal biohybrids in constrained microenvironments. By leveraging the inherent propulsion of green microalgae and external steering capabilities acquired through the magnetization of microalgal cells, our biohybrids exhibit efficient navigation in viscous and confined microenvironments. Through high-yield fabrication and magnetic manipulation, we show precise control over their movement. Our findings reveal distinct navigation patterns influenced by magnetic guidance, namely backtracking and crossing, shedding light on the unexplored dynamics of confined locomotion assisted by magnetism. Our work highlights the significance of understanding microalgal biohybrid swimming behavior, offering crucial insights for future biotechnological and biomedical applications requiring precise navigation in confined environments.

Wireless neuromodulation techniques are widely investigated to address the challenges associated with conventional neurostimulation devices. Previous research has relied on ultrasound, light and magnetic fields as the modalities for remotely powering neuronal implants. Use of magnetic fields has been promising for wireless neuronal interfaces since they have excellent tissue penetration. Magnetically powered devices typically work with >100 kHz electromagnetic fields; therefore, they are heavily dependent on the on-board electronics to regulate output signal. Moreover, use of such high frequency is a limiting factor for safe use, especially in deeper areas due to tissue absorption. Magnetoelectric (ME) approach is a promising method that stems from the magneto-electrical coupling. It is a high throughput approach for power delivery through magnetic fields in low frequency regimes compared to far-field or inductive coupling. In this study, we aim to understand how ME approach can be used to modulate neuronal behavior in non-resonant frequency regimes. We fabricated ME planar films through laminating magnetostrictive and piezoelectric components. We initially defined the output electrical potential as the main design parameter and subsequently optimize the device geometry and applied magnetic field profile to achieve the best possible performance. We were able to observe current density of ∼ 4-6 μA/cm2 in phosphate-buffered saline environment under 10 Hz input magnetic field. Lastly, we investigated neuromodulation potential of the ME films in-vitro through calcium imaging studies. Our preliminary results show that primary hippocampal neurons have significantly increased calcium influx during stimulation compared to pre-stimulation phase. Stimulation efficiency was further investigated with changing stimulation duration and input magnetic field waveforms. Overall, these results show that ME films are promising candidates of neuronal interfaces for wireless electrical modulation. Future work will be conducted to understand exact mechanisms of neuromodulation and design such interfaces in an implantable miniature form for in-vivo studies.