Universität Stuttgart

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Open Access
Designing covalent organic framework‐based light‐driven microswimmers toward therapeutic applications
(2023) Sridhar, Varun; Yildiz, Erdost; Rodríguez‐Camargo, Andrés; Lyu, Xianglong; Yao, Liang; Wrede, Paul; Aghakhani, Amirreza; Akolpoglu, Birgul M.; Podjaski, Filip; Lotsch, Bettina V.; Sitti, Metin
While micromachines with tailored functionalities enable therapeutic applications in biological environments, their controlled motion and targeted drug delivery in biological media require sophisticated designs for practical applications. Covalent organic frameworks (COFs), a new generation of crystalline and nanoporous polymers, offer new perspectives for light‐driven microswimmers in heterogeneous biological environments including intraocular fluids, thus setting the stage for biomedical applications such as retinal drug delivery. Two different types of COFs, uniformly spherical TABP‐PDA‐COF sub‐micrometer particles and texturally nanoporous, micrometer‐sized TpAzo‐COF particles are described and compared as light‐driven microrobots. They can be used as highly efficient visible‐light‐driven drug carriers in aqueous ionic and cellular media. Their absorption ranging down to red light enables phototaxis even in deeper and viscous biological media, while the organic nature of COFs ensures their biocompatibility. Their inherently porous structures with ≈2.6 and ≈3.4 nm pores, and large surface areas allow for targeted and efficient drug loading even for insoluble drugs, which can be released on demand. Additionally, indocyanine green (ICG) dye loading in the pores enables photoacoustic imaging, optical coherence tomography, and hyperthermia in operando conditions. This real‐time visualization of the drug‐loaded COF microswimmers enables unique insights into the action of photoactive porous drug carriers for therapeutic applications.
Open Access
Magnetic putty as a reconfigurable, recyclable, and accessible soft robotic material
(2023) Li, Meng; Pal, Aniket; Byun, Junghwan; Gardi, Gaurav; Sitti, Metin
Magnetically hard materials are widely used to build soft magnetic robots, providing large magnetic force/torque and macrodomain programmability. However, their high magnetic coercivity often presents practical challenges when attempting to reconfigure magnetization patterns, requiring a large magnetic field or heating. In this study, magnetic putty is introduced as a magnetically hard and soft material with large remanence and low coercivity. It is shown that the magnetization of magnetic putty can be easily reoriented with maximum magnitude using an external field that is only one‐tenth of its coercivity. Additionally, magnetic putty is a malleable, autonomous self‐healing material that can be recycled and repurposed. The authors anticipate magnetic putty could provide a versatile and accessible tool for various magnetic robotics applications for fast prototyping and explorations for research and educational purposes.
Open Access
Acoustic streaming‐induced multimodal locomotion of bubble‐based microrobots
(2023) Mahkam, Nima; Aghakhani, Amirreza; Sheehan, Devin; Gardi, Gaurav; Katzschmann, Robert; Sitti, Metin
Acoustically‐driven bubbles at the micron scale can generate strong microstreaming flows in its surrounding fluidic medium. The tunable acoustic streaming strength of oscillating microbubbles and the diversity of the generated flow patterns enable the design of fast‐moving microrobots with multimodal locomotion suitable for biomedical applications. The acoustic microrobots holding two coupled microbubbles inside a rigid body are presented; trapped bubbles inside the L‐shaped structure with different orifices generate various streaming flows, thus allowing multiple degrees of freedom in locomotion. The streaming pattern and mean streaming speed depend on the intensity and frequency of the acoustic wave, which can trigger four dominant locomotion modes in the microrobot, denoted as translational and rotational, spinning, rotational, and translational modes. Next, the effect of various geometrical and actuation parameters on the control and navigation of the microrobot is investigated. Furthermore, the surface‐slipping multimodal locomotion, flow mixing, particle manipulation capabilities, the effective interaction of high flow rates with cells, and subsequent cancerous cell lysing abilities of the proposed microrobot are demonstrated. Overall, these results introduce a design toolbox for the next generation of acoustic microrobots with higher degrees of freedom with multimodal locomotion in biomedical applications.
Open Access
Immune cell‐based microrobots for remote magnetic actuation, antitumor activity, and medical imaging
(2024) Dogan, Nihal Olcay; Suadiye, Eylül; Wrede, Paul; Lazovic, Jelena; Dayan, Cem Balda; Soon, Ren Hao; Aghakhani, Amirreza; Richter, Gunther; Sitti, Metin
Translating medical microrobots into clinics requires tracking, localization, and performing assigned medical tasks at target locations, which can only happen when appropriate design, actuation mechanisms, and medical imaging systems are integrated into a single microrobot. Despite this, these parameters are not fully considered when designing macrophage‐based microrobots. This study presents living macrophage‐based microrobots that combine macrophages with magnetic Janus particles coated with FePt nanofilm for magnetic steering and medical imaging and bacterial lipopolysaccharides for stimulating macrophages in a tumor‐killing state. The macrophage‐based microrobots combine wireless magnetic actuation, tracking with medical imaging techniques, and antitumor abilities. These microrobots are imaged under magnetic resonance imaging and optoacoustic imaging in soft‐tissue‐mimicking phantoms and ex vivo conditions. Magnetic actuation and real‐time imaging of microrobots are demonstrated under static and physiologically relevant flow conditions using optoacoustic imaging. Further, macrophage‐based microrobots are magnetically steered toward urinary bladder tumor spheroids and imaged with a handheld optoacoustic device, where the microrobots significantly reduce the viability of tumor spheroids. The proposed approach demonstrates the proof‐of‐concept feasibility of integrating macrophage‐based microrobots into clinic imaging modalities for cancer targeting and intervention, and can also be implemented for various other medical applications.
Open Access
Learning soft millirobot multimodal locomotion with sim‐to‐real transfer
(2024) Demir, Sinan Ozgun; Tiryaki, Mehmet Efe; Karacakol, Alp Can; Sitti, Metin
With wireless multimodal locomotion capabilities, magnetic soft millirobots have emerged as potential minimally invasive medical robotic platforms. Due to their diverse shape programming capability, they can generate various locomotion modes, and their locomotion can be adapted to different environments by controlling the external magnetic field signal. Existing adaptation methods, however, are based on hand‐tuned signals. Here, a learning‐based adaptive magnetic soft millirobot multimodal locomotion framework empowered by sim‐to‐real transfer is presented. Developing a data‐driven magnetic soft millirobot simulation environment, the periodic magnetic actuation signal is learned for a given soft millirobot in simulation. Then, the learned locomotion strategy is deployed to the real world using Bayesian optimization and Gaussian processes. Finally, automated domain recognition and locomotion adaptation for unknown environments using a Kullback‐Leibler divergence‐based probabilistic method are illustrated. This method can enable soft millirobot locomotion to quickly and continuously adapt to environmental changes and explore the actuation space for unanticipated solutions with minimum experimental cost.
Open Access
Task space adaptation via the learning of gait controllers of magnetic soft millirobots
(2021) Demir, Sinan O.; Culha, Utku; Karacakol, Alp C.; Pena-Francesch, Abdon; Trimpe, Sebastian; Sitti, Metin
Untethered small-scale soft robots have promising applications in minimally invasive surgery, targeted drug delivery, and bioengineering applications as they can directly and non-invasively access confined and hard-to-reach spaces in the human body. For such potential biomedical applications, the adaptivity of the robot control is essential to ensure the continuity of the operations, as task environment conditions show dynamic variations that can alter the robot’s motion and task performance. The applicability of the conventional modeling and control methods is further limited for soft robots at the small-scale owing to their kinematics with virtually infinite degrees of freedom, inherent stochastic variability during fabrication, and changing dynamics during real-world interactions. To address the controller adaptation challenge to dynamically changing task environments, we propose using a probabilistic learning approach for a millimeter-scale magnetic walking soft robot using Bayesian optimization (BO) and Gaussian processes (GPs). Our approach provides a data-efficient learning scheme by finding the gait controller parameters while optimizing the stride length of the walking soft millirobot using a small number of physical experiments. To demonstrate the controller adaptation, we test the walking gait of the robot in task environments with different surface adhesion and roughness, and medium viscosity, which aims to represent the possible conditions for future robotic tasks inside the human body. We further utilize the transfer of the learned GP parameters among different task spaces and robots and compare their efficacy on the improvement of data-efficient controller learning.
Open Access
Microrobot collectives with reconfigurable morphologies, behaviors, and functions
(2022) Gardi, Gaurav; Ceron, Steven; Wang, Wendong; Petersen, Kirstin; Sitti, Metin
Mobile microrobots, which can navigate, sense, and interact with their environment, could potentially revolutionize biomedicine and environmental remediation. Many self-organizing microrobotic collectives have been developed to overcome inherent limits in actuation, sensing, and manipulation of individual microrobots; however, reconfigurable collectives with robust transitions between behaviors are rare. Such systems that perform multiple functions are advantageous to operate in complex environments. Here, we present a versatile microrobotic collective system capable of on-demand reconfiguration to adapt to and utilize their environments to perform various functions at the air-water interface. Our system exhibits diverse modes ranging from isotropic to anisotrpic behaviors and transitions between a globally driven and a novel self-propelling behavior. We show the transition between different modes in experiments and simulations, and demonstrate various functions, using the reconfigurability of our system to navigate, explore, and interact with the environment. Such versatile microrobot collectives with globally driven and self-propelled behaviors have great potential in future medical and environmental applications.
Open Access
Micro- and nanofabrication of dynamic hydrogels with multichannel information
(2023) Zhang, Mingchao; Lee, Yohan; Zheng, Zhiqiang; Khan, Muhammad Turab Ali; Lyu, Xianglong; Byun, Junghwan; Giessen, Harald; Sitti, Metin
Creating micro/nanostructures containing multi-channel information within responsive hydrogels presents exciting opportunities for dynamically changing functionalities. However, fabricating these structures is immensely challenging due to the soft and dynamic nature of hydrogels, often resulting in unintended structural deformations or destruction. Here, we demonstrate that dehydrated hydrogels, treated by a programmable femtosecond laser, can allow for a robust fabrication of micro/nanostructures. The dehydration enhances the rigidity of the hydrogels and temporarily locks the dynamic behaviours, significantly promoting their structural integrity during the fabrication process. By utilizing versatile dosage domains of the femtosecond laser, we create micro-grooves on the hydrogel surface through the use of a high-dosage mode, while also altering the fluorescent intensity within the rest of the non-ablated areas via a low-dosage laser. In this way, we rationally design a pixel unit containing three-channel information: structural color, polarization state, and fluorescent intensity, and encode three complex image information sets into these channels. Distinct images at the same location were simultaneously printed onto the hydrogel, which can be observed individually under different imaging modes without cross-talk. Notably, the recovered dynamic responsiveness of the hydrogel enables a multi-information-encoded surface that can sequentially display different information as the temperature changes.

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