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2019


Thumb xl screenshot 2019 09 12 at 07.43.13
A Learnable Safety Measure

Heim, S., Rohr, A. V., Trimpe, S., Badri-Spröwitz, A.

Conference on Robot Learning, November 2019 (conference) Accepted

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[BibTex]

2019


[BibTex]


Thumb xl cell patterning with acoustic hologram
Acoustic Holographic Cell Patterning in a Biocompatible Hydrogel

Ma, Z., Holle, A., Melde, K., Qiu, T., Poeppel, K., Kadiri, V., Fischer, P.

Adv. Mat., October 2019 (article)

Abstract
Acoustophoresis is promising as a rapid, biocompatible, non-contact cell manipulation method, where cells are arranged along the nodes or antinodes of the acoustic field. Typically, the acoustic field is formed in a resonator, which results in highly symmetric regular patterns. However, arbitrary, non-symmetrically shaped cell assemblies are necessary to obtain the irregular cellular arrangements found in biological tissues. We show that arbitrarily shaped cell patterns can be obtained from the complex acoustic field distribution defined by an acoustic hologram. Attenuation of the sound field induces localized acoustic streaming and the resultant convection flow gently delivers the suspended cells to the image plane where they form the designed pattern. We show that the process can be implemented in a biocompatible collagen solution, which can then undergo gelation to immobilize the cell pattern inside the viscoelastic matrix. The patterned cells exhibit F-actin-based protrusions, which indicates that the cells grow and thrive within the matrix. Cell viability assays and brightfield imaging after one week confirm cell survival and that the patterns persist. Acoustophoretic cell manipulation by holographic fields thus holds promise for non-contact, long-range, long-term cellular pattern formation, with a wide variety of potential applications in tissue engineering and mechanobiology.

pf

[BibTex]


Thumb xl phantom surgery
A High-Fidelity Phantom for the Simulation and Quantitative Evaluation of Transurethral Resection of the Prostate

Choi, E., Adams, F., Gengenbacher, A., Schlager, D., Palagi, S., Müller, P., Wetterauer, U., Miernik, A., Fischer, P., Qiu, T.

Annals of Biomed. Eng., October 2019 (article)

Abstract
Transurethral resection of the prostate (TURP) is a minimally invasive endoscopic procedure that requires experience and skill of the surgeon. To permit surgical training under realistic conditions we report a novel phantom of the human prostate that can be resected with TURP. The phantom mirrors the anatomy and haptic properties of the gland and permits quantitative evaluation of important surgical performance indicators. Mixtures of soft materials are engineered to mimic the physical properties of the human tissue, including the mechanical strength, the electrical and thermal conductivity, and the appearance under an endoscope. Electrocautery resection of the phantom closely resembles the procedure on human tissue. Ultrasound contrast agent was applied to the central zone, which was not detectable by the surgeon during the surgery but showed high contrast when imaged after the surgery, to serve as a label for the quantitative evaluation of the surgery. Quantitative criteria for performance assessment are established and evaluated by automated image analysis. We present the workflow of a surgical simulation on a prostate phantom followed by quantitative evaluation of the surgical performance. Surgery on the phantom is useful for medical training, and enables the development and testing of endoscopic and minimally invasive surgical instruments.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


Thumb xl vision
Interactive Materials – Drivers of Future Robotic Systems

Fischer, P.

Adv. Mat., October 2019 (article)

Abstract
A robot senses its environment, processes the sensory information, acts in response to these inputs, and possibly communicates with the outside world. Robots generally achieve these tasks with electronics-based hardware or by receiving inputs from some external hardware. In contrast, simple microorganisms can autonomously perceive, act, and communicate via purely physicochemical processes in soft material systems. A key property of biological systems is that they are built from energy-consuming ‘active’ units. Exciting developments in material science show that even very simple artificial active building blocks can show surprisingly rich emergent behaviors. Active non-equilibrium systems are therefore predicted to play an essential role to realize interactive materials. A major challenge is to find robust ways to couple and integrate the energy-consuming building blocks to the mechanical structure of the material. However, success in this endeavor will lead to a new generation of sophisticated micro- and soft-robotic systems that can operate autonomously.

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[BibTex]


Thumb xl plasmonic dimers
Arrays of plasmonic nanoparticle dimers with defined nanogap spacers

Jeong, H., Adams, M. C., Guenther, J., Alarcon-Correa, M., Kim, I., Choi, E., Miksch, C., Mark, A. F. M., Mark, A. G., Fischer, P.

ACS Nano, September 2019 (article)

Abstract
Plasmonic molecules are building blocks of metallic nanostructures that give rise to intriguing optical phenomena with similarities to those seen in molecular systems. The ability to design plasmonic hybrid structures and molecules with nanometric resolution would enable applications in optical metamaterials and sensing that presently cannot be demonstrated, because of a lack of suitable fabrication methods allowing the structural control of the plasmonic atoms on a large scale. Here we demonstrate a wafer-scale “lithography-free” parallel fabrication scheme to realize nanogap plasmonic meta-molecules with precise control over their size, shape, material, and orientation. We demonstrate how we can tune the corresponding coupled resonances through the entire visible spectrum. Our fabrication method, based on glancing angle physical vapor deposition with gradient shadowing, permits critical parameters to be varied across the wafer and thus is ideally suited to screen potential structures. We obtain billions of aligned dimer structures with controlled variation of the spectral properties across the wafer. We spectroscopically map the plasmonic resonances of gold dimer structures and show that they not only are in good agreement with numerically modeled spectra, but also remain functional, at least for a year, in ambient conditions.

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link (url) DOI [BibTex]


Thumb xl screenshot 2019 08 30 at 15.45.28
Trunk Pitch Oscillations for Joint Load Redistribution in Humans and Humanoid Robots

Drama, Ö., Badri-Spröwitz, A.

Proceedings International Conference on Humanoid Robots, Humanoids, September 2019 (conference) Accepted

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link (url) [BibTex]

link (url) [BibTex]


Thumb xl enzyme nanonets toc
Genetically modified M13 bacteriophage nanonets for enzyme catalysis and recovery

Kadiri, V. M., Alarcon-Correa, M., Guenther, J. P., Ruppert, J., Bill, J., Rothenstein, D., Fischer, P.

Catalysts, 9, pages: 723, August 2019 (article)

Abstract
Enzyme-based biocatalysis exhibits multiple advantages over inorganic catalysts, including the biocompatibility and the unchallenged specificity of enzymes towards their substrate. The recovery and repeated use of enzymes is essential for any realistic application in biotechnology, but is not easily achieved with current strategies. For this purpose, enzymes are often immobilized on inorganic scaffolds, which could entail a reduction of the enzymes’ activity. Here, we show that immobilization to a nano-scaled biological scaffold, a nanonetwork of end-to-end cross-linked M13 bacteriophages, ensures high enzymatic activity and at the same time allows for the simple recovery of the enzymes. The bacteriophages have been genetically engineered to express AviTags at their ends, which permit biotinylation and their specific end-to-end self-assembly while allowing space on the major coat protein for enzyme coupling. We demonstrate that the phages form nanonetwork structures and that these so-called nanonets remain highly active even after re-using the nanonets multiple times in a flow-through reactor.

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link (url) DOI [BibTex]


Thumb xl special issue adv opt mat
Light-controlled micromotors and soft microrobots

Palagi, S., Singh, D. P., Fischer, P.

Adv. Opt. Mat., 7, pages: 1900370, August 2019 (article)

Abstract
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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link (url) DOI [BibTex]


Thumb xl screen shot 2019 04 18 at 5.55.23 pm
Series Elastic Behavior of Biarticular Muscle-Tendon Structure in a Robotic Leg

Ruppert, F., Badri-Spröwitz, A.

Frontiers in Neurorobotics, 64, pages: 13, 13, August 2019 (article)

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Frontiers YouTube link (url) DOI [BibTex]

Frontiers YouTube link (url) DOI [BibTex]


Thumb xl screen shot 2019 04 19 at 11.29.37 am
The positive side of damping

Heim, S., Millard, M., Le Mouel, C., Sproewitz, A.

Proceedings of AMAM, The 9th International Symposium on Adaptive Motion of Animals and Machines, August 2019 (conference) Accepted

dlg

[BibTex]

[BibTex]


Thumb xl screenshot 2019 08 19 at 13.54.21
Beyond Basins of Attraction: Quantifying Robustness of Natural Dynamics

Steve Heim, , Spröwitz, A.

IEEE Transactions on Robotics (T-RO) , 35(4), pages: 939-952, August 2019 (article)

Abstract
Properly designing a system to exhibit favorable natural dynamics can greatly simplify designing or learning the control policy. However, it is still unclear what constitutes favorable natural dynamics and how to quantify its effect. Most studies of simple walking and running models have focused on the basins of attraction of passive limit cycles and the notion of self-stability. We instead emphasize the importance of stepping beyond basins of attraction. In this paper, we show an approach based on viability theory to quantify robust sets in state-action space. These sets are valid for the family of all robust control policies, which allows us to quantify the robustness inherent to the natural dynamics before designing the control policy or specifying a control objective. We illustrate our formulation using spring-mass models, simple low-dimensional models of running systems. We then show an example application by optimizing robustness of a simulated planar monoped, using a gradient-free optimization scheme. Both case studies result in a nonlinear effective stiffness providing more robustness.

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arXiv preprint arXiv:1806.08081 T-RO link (url) DOI Project Page [BibTex]

arXiv preprint arXiv:1806.08081 T-RO link (url) DOI Project Page [BibTex]


Thumb xl marss 42 palagi
Soft Continuous Surface for Micromanipulation driven by Light-controlled Hydrogels

Choi, E., Jeong, H., Qiu, T., Fischer, P., Palagi, S.

4th IEEE International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), July 2019 (conference)

Abstract
Remotely controlled, automated actuation and manipulation at the microscale is essential for a number of micro-manufacturing, biology, and lab-on-a-chip applications. To transport and manipulate micro-objects, arrays of remotely controlled micro-actuators are required, which, in turn, typically require complex and expensive solid-state chips. Here, we show that a continuous surface can function as a highly parallel, many-degree of freedom, wirelessly-controlled microactuator with seamless deformation. The soft continuous surface is based on a hydrogel that undergoes a volume change in response to applied light. The fabrication of the hydrogels and the characterization of their optical and thermomechanical behaviors are reported. The temperature-dependent localized deformation of the hydrogel is also investigated by numerical simulations. Static and dynamic deformations are obtained in the soft material by projecting light fields at high spatial resolution onto the surface. By controlling such deformations in open loop and especially closed loop, automated photoactuation is achieved. The surface deformations are then exploited to examine how inert microbeads can be manipulated autonomously on the surface. We believe that the proposed approach suggests ways to implement universal 2D micromanipulation schemes that can be useful for automation in microfabrication and lab-on-a-chip applications.

pf

[BibTex]

[BibTex]


Thumb xl kindney phantom
Soft Phantom for the Training of Renal Calculi Diagnostics and Lithotripsy

Li., D., Suarez-Ibarrola, R., Choi, E., Jeong, M., Gratzke, C., Miernik, A., Fischer, P., Qiu, T.

41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), July 2019 (conference)

Abstract
Organ models are important for medical training and surgical planning. With the fast development of additive fabrication technologies, including 3D printing, the fabrication of 3D organ phantoms with precise anatomical features becomes possible. Here, we develop the first high-resolution kidney phantom based on soft material assembly, by combining 3D printing and polymer molding techniques. The phantom exhibits both the detailed anatomy of a human kidney and the elasticity of soft tissues. The phantom assembly can be separated into two parts on the coronal plane, thus large renal calculi are readily placed at any desired location of the calyx. With our sealing method, the assembled phantom withstands a hydraulic pressure that is four times the normal intrarenal pressure, thus it allows the simulation of medical procedures under realistic pressure conditions. The medical diagnostics of the renal calculi is performed by multiple imaging modalities, including X-ray, ultrasound imaging and endoscopy. The endoscopic lithotripsy is also successfully performed on the phantom. The use of a multifunctional soft phantom assembly thus shows great promise for the simulation of minimally invasive medical procedures under realistic conditions.

pf

[BibTex]

[BibTex]


Thumb xl marss qiu
A Magnetic Actuation System for the Active Microrheology in Soft Biomaterials

Jeong, M., Choi, E., Li., D., Palagi, S., Fischer, P., Qiu, T.

4th IEEE International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), July 2019 (conference)

Abstract
Microrheology is a key technique to characterize soft materials at small scales. The microprobe is wirelessly actuated and therefore typically only low forces or torques can be applied, which limits the range of the applied strain. Here, we report a new magnetic actuation system for microrheology consisting of an array of rotating permanent magnets, which achieves a rotating magnetic field with a spatially homogeneous high field strength of ~100 mT in a working volume of ~20×20×20 mm3. Compared to a traditional electromagnetic coil system, the permanent magnet assembly is portable and does not require cooling, and it exerts a large magnetic torque on the microprobe that is an order of magnitude higher than previous setups. Experimental results demonstrate that the measurement range of the soft gels’ elasticity covers at least five orders of magnitude. With the large actuation torque, it is also possible to study the fracture mechanics of soft biomaterials at small scales.

pf

[BibTex]

[BibTex]


Thumb xl m13 bacteriophages
Self-Assembled Phage-Based Colloids for High Localized Enzymatic Activity

Alarcon-Correa, M., Guenther, J., Troll, J., Kadiri, V. M., Bill, J., Fischer, P., Rothenstein, D.

ACS Nano, March 2019 (article)

Abstract
Catalytically active colloids are model systems for chemical motors and active matter. It is desirable to replace the inorganic catalysts and the toxic fuels that are often used, with biocompatible enzymatic reactions. However, compared to inorganic catalysts, enzyme-coated colloids tend to exhibit less activity. Here, we show that the self-assembly of genetically engineered M13 bacteriophages that bind enzymes to magnetic beads ensures high and localized enzymatic activity. These phage-decorated colloids provide a proteinaceous environment for directed enzyme immobilization. The magnetic properties of the colloidal carrier particle permit repeated enzyme recovery from a reaction solution, while the enzymatic activity is retained. Moreover, localizing the phage-based construct with a magnetic field in a microcontainer allows the enzyme-phage-colloids to function as an enzymatic micropump, where the enzymatic reaction generates a fluid flow. This system shows the fastest fluid flow reported to date by a biocompatible enzymatic micropump. In addition, it is functional in complex media including blood where the enzyme driven micropump can be powered at the physiological blood-urea concentration.

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link (url) DOI [BibTex]


Thumb xl jcp pfg nmr
Absolute diffusion measurements of active enzyme solutions by NMR

Guenther, J., Majer, G., Fischer, P.

J. Chem. Phys., 150(124201), March 2019 (article)

Abstract
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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link (url) DOI [BibTex]


Thumb xl activeoptorheologicalmedium
Chemical Nanomotors at the Gram Scale Form a Dense Active Optorheological Medium

Choudhury, U., Singh, D. P., Qiu, T., Fischer, P.

Adv. Mat., (1807382), Febuary 2019 (article)

Abstract
The rheological properties of a colloidal suspension are a function of the concentration of the colloids and their interactions. While suspensions of passive colloids are well studied and have been shown to form crystals, gels, and glasses, examples of energy‐consuming “active” colloidal suspensions are still largely unexplored. Active suspensions of biological matter, such as motile bacteria or dense mixtures of active actin–motor–protein mixtures have, respectively, reveals superfluid‐like and gel‐like states. Attractive inanimate systems for active matter are chemically self‐propelled particles. It has so far been challenging to use these swimming particles at high enough densities to affect the bulk material properties of the suspension. Here, it is shown that light‐triggered asymmetric titanium dioxide that self‐propel, can be obtained in large quantities, and self‐organize to make a gram‐scale active medium. The suspension shows an activity‐dependent tenfold reversible change in its bulk viscosity.

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link (url) DOI [BibTex]


Thumb xl hyperrayleigh
First Observation of Optical Activity in Hyper-Rayleigh Scattering

Collins, J., Rusimova, K., Hooper, D., Jeong, H. H., Ohnoutek, L., Pradaux-Caggiano, F., Verbiest, T., Carbery, D., Fischer, P., Valev, V.

Phys. Rev. X, 9(011024), January 2019 (article)

Abstract
Chiral nano- or metamaterials and surfaces enable striking photonic properties, such as negative refractive index and superchiral light, driving promising applications in novel optical components, nanorobotics, and enhanced chiral molecular interactions with light. In characterizing chirality, although nonlinear chiroptical techniques are typically much more sensitive than their linear optical counterparts, separating true chirality from anisotropy is a major challenge. Here, we report the first observation of optical activity in second-harmonic hyper-Rayleigh scattering (HRS). We demonstrate the effect in a 3D isotropic suspension of Ag nanohelices in water. The effect is 5 orders of magnitude stronger than linear optical activity and is well pronounced above the multiphoton luminescence background. Because of its sensitivity, isotropic environment, and straightforward experimental geometry, HRS optical activity constitutes a fundamental experimental breakthrough in chiral photonics for media including nanomaterials, metamaterials, and chemical molecules.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


no image
Microrobotics and Microorganisms: Biohybrid Autonomous Cellular Robots

Alapan, Y., Yasa, O., Yigit, B., Yasa, I. C., Erkoc, P., Sitti, M.

Annual Review of Control, Robotics, and Autonomous Systems, 2019 (article)

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[BibTex]

[BibTex]


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X-ray Optics Fabrication Using Unorthodox Approaches

Sanli, U., Baluktsian, M., Ceylan, H., Sitti, M., Weigand, M., Schütz, G., Keskinbora, K.

Bulletin of the American Physical Society, APS, 2019 (article)

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[BibTex]

[BibTex]


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The near and far of a pair of magnetic capillary disks

Koens, L., Wang, W., Sitti, M., Lauga, E.

Soft Matter, 2019 (article)

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[BibTex]

[BibTex]


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Review of emerging concepts in nanotoxicology: opportunities and challenges for safer nanomaterial design

Singh, A. V., Laux, P., Luch, A., Sudrik, C., Wiehr, S., Wild, A., Santamauro, G., Bill, J., Sitti, M.

Toxicology Mechanisms and Methods, 2019 (article)

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[BibTex]

[BibTex]


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Graphene oxide synergistically enhances antibiotic efficacy in Vancomycin resistance Staphylococcus aureus

Singh, V., Kumar, V., Kashyap, S., Singh, A. V., Kishore, V., Sitti, M., Saxena, P. S., Srivastava, A.

ACS Applied Bio Materials, ACS Publications, 2019 (article)

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[BibTex]

[BibTex]


Thumb xl screen shot 2019 04 19 at 11.36.04 am
Quantifying the Robustness of Natural Dynamics: a Viability Approach

Heim, S., Sproewitz, A.

Proceedings of Dynamic Walking , Dynamic Walking , 2019 (conference) Accepted

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Submission DW2019 [BibTex]

Submission DW2019 [BibTex]


no image
Microfluidics Integrated Lithography‐Free Nanophotonic Biosensor for the Detection of Small Molecules

Sreekanth, K. V., Sreejith, S., Alapan, Y., Sitti, M., Lim, C. T., Singh, R.

Advanced Optical Materials, 2019 (article)

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[BibTex]

[BibTex]


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Mobile microrobots for active therapeutic delivery

Erkoc, P., Yasa, I. C., Ceylan, H., Yasa, O., Alapan, Y., Sitti, M.

Advanced Therapeutics, Wiley Online Library, 2019 (article)

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[BibTex]

[BibTex]


no image
Electromechanical actuation of dielectric liquid crystal elastomers for soft robotics

Davidson, Z., Shahsavan, H., Guo, Y., Hines, L., Xia, Y., Yang, S., Sitti, M.

Bulletin of the American Physical Society, APS, 2019 (article)

pi

[BibTex]

[BibTex]

2018


Thumb xl toc image
Role of symmetry in driven propulsion at low Reynolds number

Sachs, J., Morozov, K. I., Kenneth, O., Qiu, T., Segreto, N., Fischer, P., Leshansky, A. M.

Phys. Rev. E, 98(6):063105, American Physical Society, December 2018 (article)

Abstract
We theoretically and experimentally investigate low-Reynolds-number propulsion of geometrically achiral planar objects that possess a dipole moment and that are driven by a rotating magnetic field. Symmetry considerations (involving parity, $\widehat{P}$, and charge conjugation, $\widehat{C}$) establish correspondence between propulsive states depending on orientation of the dipolar moment. Although basic symmetry arguments do not forbid individual symmetric objects to efficiently propel due to spontaneous symmetry breaking, they suggest that the average ensemble velocity vanishes. Some additional arguments show, however, that highly symmetrical ($\widehat{P}$-even) objects exhibit no net propulsion while individual less symmetrical ($\widehat{C}\widehat{P}$-even) propellers do propel. Particular magnetization orientation, rendering the shape $\widehat{C}\widehat{P}$-odd, yields unidirectional motion typically associated with chiral structures, such as helices. If instead of a structure with a permanent dipole we consider a polarizable object, some of the arguments have to be modified. For instance, we demonstrate a truly achiral ($\widehat{P}$- and $\widehat{C}\widehat{P}$-even) planar shape with an induced electric dipole that can propel by electro-rotation. We thereby show that chirality is not essential for propulsion due to rotation-translation coupling at low Reynolds number.

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link (url) DOI Project Page [BibTex]

2018


link (url) DOI Project Page [BibTex]


Thumb xl screenshot 2018 5 9 swimming back and forth using planar flagellar propulsion at low reynolds numbers   khalil   2018   adv ...
Swimming Back and Forth Using Planar Flagellar Propulsion at Low Reynolds Numbers

Khalil, I. S. M., Tabak, A. F., Hamed, Y., Mitwally, M. E., Tawakol, M., Klingner, A., Sitti, M.

Advanced Science, 5(2):1700461, 2018 (article)

Abstract
Abstract Peritrichously flagellated Escherichia coli swim back and forth by wrapping their flagella together in a helical bundle. However, other monotrichous bacteria cannot swim back and forth with a single flagellum and planar wave propagation. Quantifying this observation, a magnetically driven soft two‐tailed microrobot capable of reversing its swimming direction without making a U‐turn trajectory or actively modifying the direction of wave propagation is designed and developed. The microrobot contains magnetic microparticles within the polymer matrix of its head and consists of two collinear, unequal, and opposite ultrathin tails. It is driven and steered using a uniform magnetic field along the direction of motion with a sinusoidally varying orthogonal component. Distinct reversal frequencies that enable selective and independent excitation of the first or the second tail of the microrobot based on their tail length ratio are found. While the first tail provides a propulsive force below one of the reversal frequencies, the second is almost passive, and the net propulsive force achieves flagellated motion along one direction. On the other hand, the second tail achieves flagellated propulsion along the opposite direction above the reversal frequency.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


Thumb xl toc image
Optical and Thermophoretic Control of Janus Nanopen Injection into Living Cells

Maier, C. M., Huergo, M. A., Milosevic, S., Pernpeintner, C., Li, M., Singh, D. P., Walker, D., Fischer, P., Feldmann, J., Lohmüller, T.

Nano Letters, 18, pages: 7935–7941, November 2018 (article) Accepted

Abstract
Devising strategies for the controlled injection of functional nanoparticles and reagents into living cells paves the way for novel applications in nanosurgery, sensing, and drug delivery. Here, we demonstrate the light-controlled guiding and injection of plasmonic Janus nanopens into living cells. The pens are made of a gold nanoparticle attached to a dielectric alumina shaft. Balancing optical and thermophoretic forces in an optical tweezer allows single Janus nanopens to be trapped and positioned on the surface of living cells. While the optical injection process involves strong heating of the plasmonic side, the temperature of the alumina stays significantly lower, thus allowing the functionalization with fluorescently labeled, single-stranded DNA and, hence, the spatially controlled injection of genetic material with an untethered nanocarrier.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


Thumb xl content nanoroboter werden ins auge injiziert
A swarm of slippery micropropellers penetrates the vitreous body of the eye

Wu, Z., Troll, J., Jeong, H. H., Wei, Q., Stang, M., Ziemssen, F., Wang, Z., Dong, M., Schnichels, S., Qiu, T., Fischer, P.

Science Advances, 4(11):eaat4388, November 2018 (article)

Abstract
The intravitreal delivery of therapeutic agents promises major benefits in the field of ocular medicine. Traditional delivery methods rely on the random, passive diffusion of molecules, which do not allow for the rapid delivery of a concentrated cargo to a defined region at the posterior pole of the eye. The use of particles promises targeted delivery but faces the challenge that most tissues including the vitreous have a tight macromolecular matrix that acts as a barrier and prevents its penetration. Here, we demonstrate novel intravitreal delivery microvehicles slippery micropropellers that can be actively propelled through the vitreous humor to reach the retina. The propulsion is achieved by helical magnetic micropropellers that have a liquid layer coating to minimize adhesion to the surrounding biopolymeric network. The submicrometer diameter of the propellers enables the penetration of the biopolymeric network and the propulsion through the porcine vitreous body of the eye over centimeter distances. Clinical optical coherence tomography is used to monitor the movement of the propellers and confirm their arrival on the retina near the optic disc. Overcoming the adhesion forces and actively navigating a swarm of micropropellers in the dense vitreous humor promise practical applications in ophthalmology.

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Video: Nanorobots propel through the eye link (url) DOI [BibTex]

Video: Nanorobots propel through the eye link (url) DOI [BibTex]


Thumb xl universal custom complex magnetic spring design methodology
Universal Custom Complex Magnetic Spring Design Methodology

Woodward, M. A., Sitti, M.

IEEE Transactions on Magnetics, 54(1):1-13, October 2018 (article)

Abstract
A design methodology is presented for creating custom complex magnetic springs through the design of force-displacement curves. This methodology results in a magnet configuration, which will produce a desired force-displacement relationship. Initially, the problem is formulated and solved as a system of linear equations. Then, given the limited likelihood of a single solution being feasibly manufactured, key parameters of the solution are extracted and varied to create a family of solutions. Finally, these solutions are refined using numerical optimization. Given the properties of magnets, this methodology can create any well-defined function of force versus displacement and is model-independent. To demonstrate this flexibility, a number of example magnetic springs are designed; one of which, designed for use in a jumping-gliding robot's shape memory alloy actuated clutch, is manufactured and experimentally characterized. Due to the scaling of magnetic forces, the displacement region which these magnetic springs are most applicable is that of millimeters and below. However, this region is well situated for miniature robots and smart material actuators, where a tailored magnetic spring, designed to compliment a component, can enhance its performance while adding new functionality. The methodology is also expendable to variable interactions and multi-dimensional magnetic field design.

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DOI [BibTex]

DOI [BibTex]


Thumb xl toc image
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, pages: 6199-6206, International Conference on Intelligent Robots and Systems 2018, October 2018 (inproceedings)

Abstract
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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arXiv IEEE Xplore DOI Project Page [BibTex]

arXiv IEEE Xplore DOI Project Page [BibTex]


Thumb xl encyclop med robotics
Nanoscale robotic agents in biological fluids and tissues

Palagi, S., Walker, D. Q. T., Fischer, P.

In The Encyclopedia of Medical Robotics, 2, pages: 19-42, 2, (Editors: Desai, J. P. and Ferreira, A.), World Scientific, October 2018 (inbook)

Abstract
Nanorobots are untethered structures of sub-micron size that can be controlled in a non-trivial way. Such nanoscale robotic agents are envisioned to revolutionize medicine by enabling minimally invasive diagnostic and therapeutic procedures. To be useful, nanorobots must be operated in complex biological fluids and tissues, which are often difficult to penetrate. In this chapter, we first discuss potential medical applications of motile nanorobots. We briefly present the challenges related to swimming at such small scales and we survey the rheological properties of some biological fluids and tissues. We then review recent experimental results in the development of nanorobots and in particular their design, fabrication, actuation, and propulsion in complex biological fluids and tissues. Recent work shows that their nanoscale dimension is a clear asset for operation in biological tissues, since many biological tissues consist of networks of macromolecules that prevent the passage of larger micron-scale structures, but contain dynamic pores through which nanorobots can move.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Fast spatial scanning of 3D ultrasound fields via thermography

Melde, K., Qiu, T., Fischer, P.

Applied Physics Letters, 113(13):133503, September 2018 (article)

Abstract
We propose and demonstrate a thermographic method that allows rapid scanning of ultrasound fields in a volume to yield 3D maps of the sound intensity. A thin sound-absorbing membrane is continuously translated through a volume of interest while a thermal camera records the evolution of its surface temperature. The temperature rise is a function of the absorbed sound intensity, such that the thermal image sequence can be combined to reveal the sound intensity distribution in the traversed volume. We demonstrate the mapping of ultrasound fields, which is several orders of magnitude faster than scanning with a hydrophone. Our results are in very good agreement with theoretical simulations.

pf

link (url) DOI Project Page [BibTex]


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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 (article)

Abstract
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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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Uphill production of dihydrogen by enzymatic oxidation of glucose without an external energy source

Suraniti, E., Merzeau, P., Roche, J., Gounel, S., Mark, A. G., Fischer, P., Mano, N., Kuhn, A.

Nature Communications, 9(1):3229, August 2018 (article)

Abstract
Chemical systems do not allow the coupling of energy from several simple reactions to drive a subsequent reaction, which takes place in the same medium and leads to a product with a higher energy than the one released during the first reaction. Gibbs energy considerations thus are not favorable to drive e.g., water splitting by the direct oxidation of glucose as a model reaction. Here, we show that it is nevertheless possible to carry out such an energetically uphill reaction, if the electrons released in the oxidation reaction are temporarily stored in an electromagnetic system, which is then used to raise the electrons' potential energy so that they can power the electrolysis of water in a second step. We thereby demonstrate the general concept that lower energy delivering chemical reactions can be used to enable the formation of higher energy consuming reaction products in a closed system.

pf

link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Chemical micromotors self-assemble and self-propel by spontaneous symmetry breaking

Yu, T., Chuphal, P., Thakur, S., Reigh, S. Y., Singh, D. P., Fischer, P.

Chem. Comm., 54, pages: 11933-11936, August 2018 (article)

Abstract
Self-propelling chemical motors have thus far required the fabrication of Janus particles with an asymmetric catalyst distribution. Here, we demonstrate that simple, isotropic colloids can spontaneously assemble to yield dimer motors that self-propel. In a mixture of isotropic titanium dioxide colloids with photo-chemical catalytic activity and passive silica colloids, light illumination causes diffusiophoretic attractions between the active and passive particles and leads to the formation of dimers. The dimers constitute a symmetry-broken motor, whose dynamics can be fully controlled by the illumination conditions. Computer simulations reproduce the dynamics of the colloids and are in good agreement with experiments. The current work presents a simple route to obtain large numbers of self-propelling chemical motors from a dispersion of spherically symmetric colloids through spontaneous symmetry breaking.

pf

link (url) DOI [BibTex]

link (url) DOI [BibTex]


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A machine from machines

Fischer, P.

Nature Physics, 14, pages: 1072–1073, July 2018 (misc)

Abstract
Building spinning microrotors that self-assemble and synchronize to form a gear sounds like an impossible feat. However, it has now been achieved using only a single type of building block -- a colloid that self-propels.

pf

link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Chemotaxis of Active Janus Nanoparticles

Popescu, M. N., Uspal, W. E., Bechinger, C., Fischer, P.

Nano Letters, 18(9):5345–5349, July 2018 (article)

Abstract
While colloids and molecules in solution exhibit passive Brownian motion, particles that are partially covered with a catalyst, which promotes the transformation of a fuel dissolved in the solution, can actively move. These active Janus particles are known as “chemical nanomotors” or self-propelling “swimmers” and have been realized with a range of catalysts, sizes, and particle geometries. Because their active translation depends on the fuel concentration, one expects that active colloidal particles should also be able to swim toward a fuel source. Synthesizing and engineering nanoparticles with distinct chemotactic properties may enable important developments, such as particles that can autonomously swim along a pH gradient toward a tumor. Chemotaxis requires that the particles possess an active coupling of their orientation to a chemical gradient. In this Perspective we provide a simple, intuitive description of the underlying mechanisms for chemotaxis, as well as the means to analyze and classify active particles that can show positive or negative chemotaxis. The classification provides guidance for engineering a specific response and is a useful organizing framework for the quantitative analysis and modeling of chemotactic behaviors. Chemotaxis is emerging as an important focus area in the field of active colloids and promises a number of fascinating applications for nanoparticles and particle-based delivery.

pf

link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Programmable collective behavior in dynamically self-assembled mobile microrobotic swarms

B Yigit, , Y Alapan, , Sitti, M.

Advanced Science, July 2018 (article)

Abstract
Collective control of mobile microrobotic swarms is indispensable for their potential high-impact applications in targeted drug delivery, medical diagnostics, parallel micromanipulation, and environmental sensing and remediation. Lack of on-board computational and sensing capabilities in current microrobotic systems necessitates use of physical interactions among individual microrobots for local physical communication and cooperation. Here, we show that mobile microrobotic swarms with well-defined collective behavior can be designed by engineering magnetic interactions among individual units. Microrobots, consisting of a linear chain of self-assembled magnetic microparticles, locomote on surfaces in response to a precessing magnetic field. Control over the direction of precessing magnetic field allows engineering attractive and repulsive interactions among microrobots and, thus, collective order with well-defined spatial organization and parallel operation over macroscale distances (~ 1 cm). These microrobotic swarms can be guided through confined spaces, while preserving microrobot morphology and function. These swarms can further achieve directional transport of large cargoes on surfaces and small cargoes in bulk fluids. Described design approach, exploiting physical interactions among individual robots, enables facile and rapid formation of self-organized and reconfigurable microrobotic swarms with programmable collective order.

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link (url) [BibTex]


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3D-Printed Biodegradable Microswimmer for Drug Delivery and Targeted Cell Labeling

Hakan Ceylan, , I. Ceren Yasa, , Oncay Yasa, , Ahmet Fatih Tabak, , Joshua Giltinan, , Sitti, M.

bioRxiv, pages: 379024, July 2018 (article)

Abstract
Miniaturization of interventional medical devices can leverage minimally invasive technologies by enabling operational resolution at cellular length scales with high precision and repeatability. Untethered micron-scale mobile robots can realize this by navigating and performing in hard-to-reach, confined and delicate inner body sites. However, such a complex task requires an integrated design and engineering strategy, where powering, control, environmental sensing, medical functionality and biodegradability need to be considered altogether. The present study reports a hydrogel-based, biodegradable microrobotic swimmer, which is responsive to the changes in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical magnetic microswimmer of 20 micrometers length, which is 3D-printed with complex geometrical and compositional features. At normal physiological concentrations, matrix metalloproteinase-2 (MMP-2) enzyme can entirely degrade the microswimmer body in 118 h to solubilized non-toxic products. The microswimmer can respond to the pathological concentrations of MMP-2 by swelling and thereby accelerating the release kinetics of the drug payload. Anti-ErbB 2 antibody-tagged magnetic nanoparticles released from the degraded microswimmers serve for targeted labeling of SKBR3 breast cancer cells to realize the potential of medical imaging of local tissue sites following the therapeutic intervention. These results represent a leap forward toward clinical medical microrobots that are capable of sensing, responding to the local pathological information, and performing specific therapeutic and diagnostic tasks as orderly executed operations using their smart composite material architectures.

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DOI Project Page [BibTex]


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Innate turning preference of leaf-cutting ants in the absence of external orientation cues

Endlein, T., Sitti, M.

Journal of Experimental Biology, The Company of Biologists Ltd, June 2018 (article)

Abstract
Many ants use a combination of cues for orientation but how do ants find their way when all external cues are suppressed? Do they walk in a random way or are their movements spatially oriented? Here we show for the first time that leaf-cutting ants (Acromyrmex lundii) have an innate preference of turning counter-clockwise (left) when external cues are precluded. We demonstrated this by allowing individual ants to run freely on the water surface of a newly-developed treadmill. The surface tension supported medium-sized workers but effectively prevented ants from reaching the wall of the vessel, important to avoid wall-following behaviour (thigmotaxis). Most ants ran for minutes on the spot but also slowly turned counter-clockwise in the absence of visual cues. Reconstructing the effectively walked path revealed a looping pattern which could be interpreted as a search strategy. A similar turning bias was shown for groups of ants in a symmetrical Y-maze where twice as many ants chose the left branch in the absence of optical cues. Wall-following behaviour was tested by inserting a coiled tube before the Y-fork. When ants traversed a left-coiled tube, more ants chose the left box and vice versa. Adding visual cues in form of vertical black strips either outside the treadmill or on one branch of the Y-maze led to oriented walks towards the strips. It is suggested that both, the turning bias and the wall-following are employed as search strategies for an unknown environment which can be overridden by visual cues.

pi

link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Motility and chemotaxis of bacteria-driven microswimmers fabricated using antigen 43-mediated biotin display

Schauer, O., Mostaghaci, B., Colin, R., Hürtgen, D., Kraus, D., Sitti, M., Sourjik, V.

Scientific Reports, 8(1):9801, Nature Publishing Group, June 2018 (article)

Abstract
Bacteria-driven biohybrid microswimmers (bacteriabots) combine synthetic cargo with motile living bacteria that enable propulsion and steering. Although fabrication and potential use of such bacteriabots have attracted much attention, existing methods of fabrication require an extensive sample preparation that can drastically decrease the viability and motility of bacteria. Moreover, chemotactic behavior of bacteriabots in a liquid medium with chemical gradients has remained largely unclear. To overcome these shortcomings, we designed Escherichia coli to autonomously display biotin on its cell surface via the engineered autotransporter antigen 43 and thus to bind streptavidin-coated cargo. We show that the cargo attachment to these bacteria is greatly enhanced by motility and occurs predominantly at the cell poles, which is greatly beneficial for the fabrication of motile bacteriabots. We further performed a systemic study to understand and optimize the ability of these bacteriabots to follow chemical gradients. We demonstrate that the chemotaxis of bacteriabots is primarily limited by the cargo-dependent reduction of swimming speed and show that the fabrication of bacteriabots using elongated E. coli cells can be used to overcome this limitation.

pi

link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Multifunctional ferrofluid-infused surfaces with reconfigurable multiscale topography

Wang, W., Timonen, J. V. I., Carlson, A., Drotlef, D., Zhang, C. T., Kolle, S., Grinthal, A., Wong, T., Hatton, B., Kang, S. H., Kennedy, S., Chi, J., Blough, R. T., Sitti, M., Mahadevan, L., Aizenberg, J.

Nature, June 2018 (article)

Abstract
Developing adaptive materials with geometries that change in response to external stimuli provides fundamental insights into the links between the physical forces involved and the resultant morphologies and creates a foundation for technologically relevant dynamic systems1,2. In particular, reconfigurable surface topography as a means to control interfacial properties 3 has recently been explored using responsive gels 4 , shape-memory polymers 5 , liquid crystals6-8 and hybrid composites9-14, including magnetically active slippery surfaces12-14. However, these designs exhibit a limited range of topographical changes and thus a restricted scope of function. Here we introduce a hierarchical magneto-responsive composite surface, made by infiltrating a ferrofluid into a microstructured matrix (termed ferrofluid-containing liquid-infused porous surfaces, or FLIPS). We demonstrate various topographical reconfigurations at multiple length scales and a broad range of associated emergent behaviours. An applied magnetic-field gradient induces the movement of magnetic nanoparticles suspended in the ferrofluid, which leads to microscale flow of the ferrofluid first above and then within the microstructured surface. This redistribution changes the initially smooth surface of the ferrofluid (which is immobilized by the porous matrix through capillary forces) into various multiscale hierarchical topographies shaped by the size, arrangement and orientation of the confining microstructures in the magnetic field. We analyse the spatial and temporal dynamics of these reconfigurations theoretically and experimentally as a function of the balance between capillary and magnetic pressures15-19 and of the geometric anisotropy of the FLIPS system. Several interesting functions at three different length scales are demonstrated: self-assembly of colloidal particles at the micrometre scale; regulated flow of liquid droplets at the millimetre scale; and switchable adhesion and friction, liquid pumping and removal of biofilms at the centimetre scale. We envision that FLIPS could be used as part of integrated control systems for the manipulation and transport of matter, thermal management, microfluidics and fouling-release materials.

pi

link (url) DOI [BibTex]

link (url) DOI [BibTex]