Micro, Nano, and Molecular Systems Members Publications

Members

Micro, Nano, and Molecular Systems
Micro, Nano, and Molecular Systems
PostDoc, now Center for Micro-BioRobotics@SSSA (Pisa, Italy) of Istituto Italiano di Tecnologia, Italy.
Micro, Nano, and Molecular Systems
Univ. of Stuttgart CyberValley Group Leader & MPI Senior Research Scientist
Micro, Nano, and Molecular Systems
Micro, Nano, and Molecular Systems
Professor

Publications

Micro, Nano, and Molecular Systems Article Comment on “Boosted molecular mobility during common chemical reactions” Günther, J., Fillbrook, L. L., MacDonald, T. S., Majer, G., Price, W. S., Fischer, P., Beves, J. E. Science, 371(6526):eabe8322, January 2021
The apparent “boosted mobility” observed by Wang et al. (Reports, 31 July 2020, p. 537) is the result of a known artifact. When signal intensities are changing during a nuclear magnetic resonance (NMR) diffusion measurement for reasons other than diffusion, the use of monotonically increasing gradient amplitudes produces erroneous diffusion coefficients. We show that no boosted molecular mobility is observed when shuffled gradient amplitudes are applied.
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Micro, Nano, and Molecular Systems Article Light-controlled micromotors and soft microrobots Palagi, S., Singh, D. P., Fischer, P. Adv. Opt. Mat., 7:1900370, August 2019
Mobile microscale devices and microrobots can be powered by catalytic reactions (chemical micromotors) or by external fields. This report is focused on the role of light as a versatile means for wirelessly powering and controlling such microdevices. Recent advances in the development of autonomous micromotors are discussed, where light permits their actuation with unprecedented control and thereby enables advances in the field of active matter. In addition, structuring the light field is a new means to drive soft microrobots that are based on (photo‐) responsive polymers. The behavior of the two main classes of thermo‐ and photoresponsive polymers adopted in microrobotics (poly(N‐isopropylacrylamide) and liquid‐crystal elastomers) is analyzed, and recent applications are reported. The advantages and limitations of controlling micromotors and microrobots by light are reviewed, and some of the remaining challenges in the development of novel photo‐active materials for micromotors and microrobots are discussed.
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Micro, Nano, and Molecular Systems Article Absolute diffusion measurements of active enzyme solutions by NMR Guenther, J., Majer, G., Fischer, P. J. Chem. Phys., 150(124201), March 2019
The diffusion of enzymes is of fundamental importance for many biochemical processes. Enhanced or directed enzyme diffusion can alter the accessibility of substrates and the organization of enzymes within cells. Several studies based on fluorescence correlation spectroscopy (FCS) report enhanced diffusion of enzymes upon interaction with their substrate or inhibitor. In this context, major importance is given to the enzyme fructose-bisphosphate aldolase, for which enhanced diffusion has been reported even though the catalysed reaction is endothermic. Additionally, enhanced diffusion of tracer particles surrounding the active aldolase enzymes has been reported. These studies suggest that active enzymes can act as chemical motors that self-propel and give rise to enhanced diffusion. However, fluorescence studies of enzymes can, despite several advantages, suffer from artefacts. Here we show that the absolute diffusion coefficients of active enzyme solutions can be determined with Pulsed Field Gradient Nuclear Magnetic Resonance (PFG-NMR). The advantage of PFG-NMR is that the motion of the molecule of interest is directly observed in its native state without the need for any labelling. Further, PFG-NMR is model-free and thus yields absolute diffusion constants. Our PFG-NMR experiments of solutions containing active fructose-bisphosphate aldolase from rabbit muscle do not show any diffusion enhancement for the active enzymes nor the surrounding molecules. Additionally, we do not observe any diffusion enhancement of aldolase in the presence of its inhibitor pyrophosphate.
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Intelligent Control Systems Micro, Nano, and Molecular Systems Conference Paper Gait learning for soft microrobots controlled by light fields Rohr, A. V., Trimpe, S., Marco, A., Fischer, P., Palagi, S. In International Conference on Intelligent Robots and Systems (IROS) 2018, 6199-6206, Piscataway, NJ, USA, International Conference on Intelligent Robots and Systems, October 2018 (Published)
Soft microrobots based on photoresponsive materials and controlled by light fields can generate a variety of different gaits. This inherent flexibility can be exploited to maximize their locomotion performance in a given environment and used to adapt them to changing environments. However, because of the lack of accurate locomotion models, and given the intrinsic variability among microrobots, analytical control design is not possible. Common data-driven approaches, on the other hand, require running prohibitive numbers of experiments and lead to very sample-specific results. Here we propose a probabilistic learning approach for light-controlled soft microrobots based on Bayesian Optimization (BO) and Gaussian Processes (GPs). The proposed approach results in a learning scheme that is highly data-efficient, enabling gait optimization with a limited experimental budget, and robust against differences among microrobot samples. These features are obtained by designing the learning scheme through the comparison of different GP priors and BO settings on a semisynthetic data set. The developed learning scheme is validated in microrobot experiments, resulting in a 115% improvement in a microrobot’s locomotion performance with an experimental budget of only 20 tests. These encouraging results lead the way toward self-adaptive microrobotic systems based on lightcontrolled soft microrobots and probabilistic learning control.
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Micro, Nano, and Molecular Systems Article Diffusion Measurements of Swimming Enzymes with Fluorescence Correlation Spectroscopy Günther, J., Börsch, M., Fischer, P. Accounts of Chemical Research, 51(9):1911-1920, August 2018 (Published)
Self-propelled chemical motors are chemically powered micro- or nanosized swimmers. The energy required for these motors’ active motion derives from catalytic chemical reactions and the transformation of a fuel dissolved in the solution. While self-propulsion is now well established for larger particles, it is still unclear if enzymes, nature’s nanometer-sized catalysts, are potentially also self-powered nanomotors. Because of its small size, any increase in an enzyme’s diffusion due to active self-propulsion must be observed on top of the enzyme’s passive Brownian motion, which dominates at this scale. Fluorescence correlation spectroscopy (FCS) is a sensitive method to quantify the diffusion properties of single fluorescently labeled molecules in solution. FCS experiments have shown a general increase in the diffusion constant of a number of enzymes when the enzyme is catalytically active. Diffusion enhancements after addition of the enzyme’s substrate (and sometimes its inhibitor) of up to 80\% have been reported, which is at least 1 order of magnitude higher than what theory would predict. However, many factors contribute to the FCS signal and in particular the shape of the autocorrelation function, which underlies diffusion measurements by fluorescence correlation spectroscopy. These effects need to be considered to establish if and by how much the catalytic activity changes an enzyme’s diffusion.We carefully review phenomena that can play a role in FCS experiments and the determination of enzyme diffusion, including the dissociation of enzyme oligomers upon interaction with the substrate, surface binding of the enzyme to glass during the experiment, conformational changes upon binding, and quenching of the fluorophore. We show that these effects can cause changes in the FCS signal that behave similar to an increase in diffusion. However, in the case of the enzymes F1-ATPase and alkaline phosphatase, we demonstrate that there is no measurable increase in enzyme diffusion. Rather, dissociation and conformational changes account for the changes in the FCS signal in the former and fluorophore quenching in the latter. Within the experimental accuracy of our FCS measurements, we do not observe any change in diffusion due to activity for the enzymes we have investigated.We suggest useful control experiments and additional tests for future FCS experiments that should help establish if the observed diffusion enhancement is real or if it is due to an experimental or data analysis artifact. We show that fluorescence lifetime and mean intensity measurements are essential in order to identify the nature of the observed changes in the autocorrelation function. While it is clear from theory that chemically active enzymes should also act as self-propelled nanomotors, our FCS measurements show that the associated increase in diffusion is much smaller than previously reported. Further experiments are needed to quantify the contribution of the enzymes’ catalytic activity to their self-propulsion. We hope that our findings help to establish a useful protocol for future FCS studies in this field and help establish by how much the diffusion of an enzyme is enhanced through catalytic activity.
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Micro, Nano, and Molecular Systems Article Bioinspired microrobots Palagi, S., Fischer, P. Nature Reviews Materials, 3:113–124, May 2018 (Published)
Microorganisms can move in complex media, respond to the environment and self-organize. The field of microrobotics strives to achieve these functions in mobile robotic systems of sub-millimetre size. However, miniaturization of traditional robots and their control systems to the microscale is not a viable approach. A promising alternative strategy in developing microrobots is to implement sensing, actuation and control directly in the materials, thereby mimicking biological matter. In this Review, we discuss design principles and materials for the implementation of robotic functionalities in microrobots. We examine different biological locomotion strategies, and we discuss how they can be artificially recreated in magnetic microrobots and how soft materials improve control and performance. We show that smart, stimuli-responsive materials can act as on-board sensors and actuators and that ‘active matter’ enables autonomous motion, navigation and collective behaviours. Finally, we provide a critical outlook for the field of microrobotics and highlight the challenges that need to be overcome to realize sophisticated microrobots, which one day might rival biological machines.
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Micro, Nano, and Molecular Systems Patent Ultrasonic actuator device and applications thereof Qiu, T., Fischer, P. (US10008960B2), January 2018
ltrasonic actuator device (100) includes actuator arm arrangement (10) including first and second actuator sections (11,12), wherein the first section is arranged for coupling with support structure (50) and the second section is movable relative to the first section, and ultrasonic driver device (20) including at least one ultrasonic driver unit (21-28) coupled with at least one of first and second sections for driving actuator arm arrangement (10) and for providing movement of the second section relative to the first section, and wherein actuator arm arrangement (10) is movable with at least two degrees of freedom and the at least one ultrasonic driver unit includes an array of oscillating elements being arranged for creating an acoustic stream in an adjacent medium in response to application of ultrasound. Furthermore, an operational instrument including at least one ultrasonic actuator device (100) and a method of using the device are described.
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Micro, Nano, and Molecular Systems Article Wireless Acoustic-Surface Actuators for Miniaturized Endoscopes Qiu, T., Adams, F., Palagi, S., Melde, K., Mark, A. G., Wetterauer, U., Miernik, A., Fischer, P. ACS Applied Materials & Interfaces, 9(49):42536 - 42543, November 2017 (Published)
Endoscopy enables minimally invasive procedures in many medical fields, such as urology. However, current endoscopes are normally cable-driven, which limits their dexterity and makes them hard to miniaturize. Indeed current urological endoscopes have an outer diameter of about 3 mm and still only possess one bending degree of freedom. In this paper, we report a novel wireless actuation mechanism that increases the dexterity and that permits the miniaturization of a urological endoscope. The novel actuator consists of thin active surfaces that can be readily attached to any device and are wirelessly powered by ultrasound. The surfaces consist of two-dimensional arrays of micro-bubbles, which oscillate under ultrasound excitation and thereby generate an acoustic streaming force. Bubbles of different sizes are addressed by their unique resonance frequency, thus multiple degrees of freedom can readily be incorporated. Two active miniaturized devices (with a side length of around 1 mm) are demonstrated: a miniaturized mechanical arm that realizes two degrees of freedom, and a flexible endoscope prototype equipped with a camera at the tip. With the flexible endoscope, an active endoscopic examination is successfully performed in a rabbit bladder. This results show the potential medical applicability of surface actuators wirelessly powered by ultrasound penetrating through biological tissues.
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Micro, Nano, and Molecular Systems Article Non-Equilibrium Assembly of Light-Activated Colloidal Mixtures Singh, D. P., Choudhury, U., Fischer, P., Mark, A. G. Advanced Materials, 29:1701328, June 2017, 32 (Published)
The collective phenomena exhibited by artificial active matter systems present novel routes to fabricating out-of-equilibrium microscale assemblies. Here, the crystallization of passive silica colloids into well-controlled 2D assemblies is shown, which is directed by a small number of self-propelled active colloids. The active colloids are titania–silica Janus particles that are propelled when illuminated by UV light. The strength of the attractive interaction and thus the extent of the assembled clusters can be regulated by the light intensity. A remarkably small number of the active colloids is sufficient to induce the assembly of the dynamic crystals. The approach produces rationally designed colloidal clusters and crystals with controllable sizes, shapes, and symmetries. This multicomponent active matter system offers the possibility of obtaining structures and assemblies that cannot be found in equilibrium systems.
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Micro, Nano, and Molecular Systems Article Wireless actuation with functional acoustic surfaces Qiu, T., Palagi, S., Mark, A. G., Melde, K., Adams, F., Fischer, P. Appl. Phys. Lett., 109(19):191602, November 2016, APL Editor's pick. APL News. (Published)
Miniaturization calls for micro-actuators that can be powered wirelessly and addressed individually. Here, we develop functional surfaces consisting of arrays of acoustically resonant microcavities, and we demonstrate their application as two-dimensional wireless actuators. When remotely powered by an acoustic field, the surfaces provide highly directional propulsive forces in fluids through acoustic streaming. A maximal force of similar to 0.45mN is measured on a 4 x 4 mm(2) functional surface. The response of the surfaces with bubbles of different sizes is characterized experimentally. This shows a marked peak around the micro-bubbles' resonance frequency, as estimated by both an analytical model and numerical simulations. The strong frequency dependence can be exploited to address different surfaces with different acoustic frequencies, thus achieving wireless actuation with multiple degrees of freedom. The use of the functional surfaces as wireless ready-to-attach actuators is demonstrated by implementing a wireless and bidirectional miniaturized rotary motor, which is 2.6 x 2.6 x 5 mm(3) in size and generates a stall torque of similar to 0.5 mN.mm. The adoption of micro-structured surfaces as wireless actuators opens new possibilities in the development of miniaturized devices and tools for fluidic environments that are accessible by low intensity ultrasound fields.
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Micro, Nano, and Molecular Systems Article Structured light enables biomimetic swimming and versatile locomotion of photoresponsive soft microrobots Palagi, S., Mark, A. G., Reigh, S. Y., Melde, K., Qiu, T., Zeng, H., Parmeggiani, C., Martella, D., Sanchez-Castillo, A., Kapernaum, N., Giesselmann, F., Wiersma, D. S., Lauga, E., Fischer, P. Nature Materials, 15(6):647–653, November 2016, Max Planck press release, Nature News & Views. (Published)
Microorganisms move in challenging environments by periodic changes in body shape. In contrast, current artificial microrobots cannot actively deform, exhibiting at best passive bending under external fields. Here, by taking advantage of the wireless, scalable and spatiotemporally selective capabilities that light allows, we show that soft microrobots consisting of photoactive liquid-crystal elastomers can be driven by structured monochromatic light to perform sophisticated biomimetic motions. We realize continuum yet selectively addressable artificial microswimmers that generate travelling-wave motions to self-propel without external forces or torques, as well as microrobots capable of versatile locomotion behaviours on demand. Both theoretical predictions and experimental results confirm that multiple gaits, mimicking either symplectic or antiplectic metachrony of ciliate protozoa, can be achieved with single microswimmers. The principle of using structured light can be extended to other applications that require microscale actuation with sophisticated spatiotemporal coordination for advanced microrobotic technologies.
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Micro, Nano, and Molecular Systems Conference Paper Wireless actuator based on ultrasonic bubble streaming Qiu, T., Palagi, S., Mark, A. G., Melde, K., Fischer, P. In 2016 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), 1-5, Piscataway, NJ, USA, July 2016 (Published)
Miniaturized actuators are a key element for the manipulation and automation at small scales. Here, we propose a new miniaturized actuator, which consists of an array of micro gas bubbles immersed in a fluid. Under ultrasonic excitation, the oscillation of micro gas bubbles results in acoustic streaming and provides a propulsive force that drives the actuator. The actuator was fabricated by lithography and fluidic streaming was observed under ultrasound excitation. Theoretical modelling and numerical simulations were carried out to show that lowing the surface tension results in a larger amplitude of the bubble oscillation, and thus leads to a higher propulsive force. Experimental results also demonstrate that the propulsive force increases 3.5 times when the surface tension is lowered by adding a surfactant. An actuator with a 4×4 mm 2 surface area provides a driving force of about 0.46 mN, suggesting that it is possible to be used as a wireless actuator for small-scale robots and medical instruments.
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