34 results
(View BibTeX file of all listed publications)
2021
Magnetic Micro-/Nanopropellers for Biomedicine
Qiu, T., Jeong, M., Goyal, R., Kadiri, V., Sachs, J., Fischer, P.
In Field-Driven Micro and Nanorobots for Biology and Medicine, pages: 389-410, 16, (Editors: Sun, Y. and Wang, X. and Yu, J.), Springer Nature, November 2021 (inbook)
In nature, many bacteria swim by rotating their helical flagella. A particularly promising class of artificial micro- and nano-robots mimic this propeller-like propulsion mechanism to move through fluids and tissues for applications in minimally-invasive medicine. Several fundamental challenges have to be overcome in order to build micro-machines that move similar to bacteria for in vivo applications. Here, we review recent advances of magnetically-powered micro-/nano-propellers. Four important aspects of the propellers – the geometrical shape, the fabrication method, the generation of magnetic fields for actuation, and the choice of biocompatible magnetic materials – are highlighted. First, the fundamental requirements are elucidated that arise due to hydrodynamics at low Reynolds (Re) number. We discuss the role that the propellers’ shape and symmetry play in realizing effective propulsion at low Re. Second, the additive nano-fabrication method Glancing Angle Deposition is discussed as a versatile technique to quickly grow large numbers of designer nano-helices. Third, systems to generate rotating magnetic fields via permanent magnets or electromagnetic coils are presented. And finally, the biocompatibility of the magnetic materials is discussed. Iron-platinum is highlighted due to its biocompatibility and its superior magnetic properties, which is promising for targeted delivery, minimally-invasive magnetic nano-devices and biomedical applications.
Chemically active micromotors
University of Stuttgart, Stuttgart, July 2021 (phdthesis)
Motion is a mark of living systems. It is realised by energy conversion to perform vital tasks and is thus of great importance for all living systems. One approach to achieve motion is by including active motion of micro/nano objects. Unlike in the fluid at the macro scale, active swimming cannot be achieved by reciprocal movements at the micro scale. Breaking symmetry at the micro scale thus becomes a critical issue. The challenge is that this often requires outside intervention to build systems that already show symmetry breaking. And another challenge is that there are few examples where active microscale motion can cause a macroscopic effect, or facilitate a useful application.
In the first part of the thesis, the first challenge is addressed and a new route of spontaneous symmetry breaking is developed. Microscale motion in artificial chemical systems has thus far been realised in chemical motion. These are microparticles that are fabricated to possess two different halves, known as Janus particles. One half is catalytically active and drives the self-phoretics. The Janus micromotors are generally fabricated using fabrication techniques such as PVD, CVD. These techniques require deposition onto a surface, which limit the number of structures that can be fabricated.
In this work, we show that two species of isotropic (symmetric) micro particles, one is a photocatalytically active particle TiO2, the other is a passive SiO2 particle can spontaneously form a dimer structure. Under UV illumination, a chemical gradient is generated around the photo active particles. The passive particle is attracted toward the highest chemical concentration of the reaction product towards the active particle. A dimer forms that starts to self-propel. The speed of the dimer can be controlled by adjusting the UV intensity.
The mechanism of the dimer formation is examined and shown to be due to a diffusiophoretic interaction between the active and the passive particle. The interaction force and the propulsion of the dimer swimmers are examined. The role of salts, particle size and concentration are studied. An additional repulsion interaction is observed between two active particles. An optimal volumetric particle density of ≤ 2% is identified for dimer formation and the dimers remain active for > 20s. This thesis thereby demonstrates a self-assembly route where the chemical activity causes dimer formation and thus spontaneous symmetry breaking which does not require any physical fabrication steps.
Most work thus far has studied the behaviour of individual chemical micromotors (Janus particles) at the micro scale. To induce a macroscopic effect and facilitate an application using individual micro/nano active particles requires cooperative effects of many "micromotors". Therefore, we developed a novel fabrication method which allows a large number of Janus structures to be assembled in an ordered manner. We fabricated an array of photoactive Janus micro structures on a surface by glancing angle deposition (GLAD) onto a photolithography patterned substrate. Illuminating the surface of Janus array structures with UV light initiates the water splitting reaction, which produces an osmotic flow around the micro structures. The osmotic flow at each structure is coupled with the flows generated by the neighbouring particles. The microscopic osmotic flow thereby results in a macroscopic fluid flow. By adjusting the spacing between single micro structures, an optimised pumping velocity is achieved with a micro pillar diameter of 2 μm and a spacing of ∼ 2 μm. We compared the pumping performance of the micro pillar array with other topological chemical structures, such as micro Janus bar arrays and 2D micro Janus disk arrays, and find that the 3D structure is essential to generate a chemical gradient on the surface. We believe that this is the first chemical micropump formed by chemically active Janus structures. The active pumping surface can provide a flow speed of up to 4 μm/s.
This active surface consisting of micropillar arrays can be easily integrated in most microchannels and serve as an on-board micropump. A theoretical model and numerical simulations are presented to describe the microchannel pumping. The theory reproduces the experimentally measured flow profiles very well. We have thus established a new type of chemical pump, which can wirelessly pump fluid in a microchannel, and the pumping volume rate and flow profile can be modified simply by changing the nature and orientation of the self-pumping walls.
Advanced Diffusion Studies of Active Enzymes and Nanosystems
Universität Stuttgart, Stuttgart (und Cuvillier Verlag, Göttingen), February 2021 (phdthesis)
Enzymes are fascinating chemical nanomachines that catalyze many reactions, which are essential for life. Studying enzymes is therefore important in a biological and medical context, but the catalytic potential of enzymes also finds use in organic synthesis. This thesis is concerned with the fundamental question whether the catalytic reaction of an enzyme or molecular catalyst can cause it to show enhanced diffusion. Diffusion measurements were performed with advanced fluorescence correlation spectroscopy (FCS) and diffusion nuclear magnetic resonance (NMR) spectroscopy techniques. The measurement results lead to the unraveling of artefacts in enzyme FCS and molecular NMR measurements, and thus seriously question several recent publications, which claim that enzymes and molecular catalysts are active matter and experience enhanced diffusion. In addition to these fundamental questions, this thesis also examines the use of enzymes as biocatalysts. A novel nanoconstruct – the enzyme-phage-colloid (E-P-C) – is presented, which utilizes filamentous viruses as immobilization templates for enzymes. E-P-Cs can be used for biocatalysis with convenient magnetic recovery of enzymes and serve as enzymatic micropumps. The latter can autonomously pump blood at physiological urea concentrations.
2020
Motion, Symmetry & Spectroscopy of Chiral Nanostructures
Universität Stuttgart, Stuttgart (und Springer, Cham), July 2020 (phdthesis)
Nanostructures are of interest for a broad spectrum of potential applications. For biomedical tasks, small nanoswimmers could help realize targeted drug delivery or minimally invasive surgery, which necessitates a comprehensive understanding and control of their motion. As an optical sensor, single plasmonic nanostructures can enhance the weak optical signals associated with biologically-important handed (chiral) molecules, and thus potentially lead to much higher detection sensitivities and improved selectivities. Both, the motion and spectroscopic behavior of nanostructures is closely related to the symmetry they possess. For propulsion at small scales it is well known that symmetry is important. For instance, the bacterial flagellum has a chiral corkscrew shape to allow non-reciprocal motion. One can therefore wonder if chirality is essential, and if indeed this is the simplest shape for propulsion, or if other structures – possibly ones that are simpler to fabricate – can also show propulsion when they are rotated. Another aspect that relates to the symmetry is the spectroscopic observation of nanostructures. Especially in chiral structures both the shape itself as well as the orientation in space determines optical signals. It is therefore important to be able to dis-entangle these effects.
To shed light on this, this thesis presents experiments that capture the active motion and chiroptical spectroscopy of artificial nanostructures at low Reynolds number (Re), and examines the role chirality plays in these phenomena. Against previous expectations and reports, it is shown that a propeller does not need to be chiral to locomote and the first truly achiral propeller at low Re is reported. Similarly, a careful examination of the spectroscopy of plasmonic nanostructures shows that structures do not need to be chiral to give rise to chiroptical signals. A novel spectrometer was constructed to observe individual nanostructures. Thereby it has been possible to identify an observable, which has not been measured previously – that permits the true chiroptical spectrum to be obtained from a single nanoparticle suspended in solution. The basis for the presented experiments is the fabrication of micro- and nanostructures with simple and complex, achiral and chiral shapes via Glancing Angle Deposition (GLAD).
The first part of this thesis considers active motion exhibited by highly symmetric micro- and nanoswimmers. Owing to the scallop theorem, reciprocal motion does not lead to a net translation at low Re, and other swimming strategies must be exploited, e.g. rotation-translation coupling. Previously, chirality was assumed to be required to efficiently couple rotation to translation at low Re, as is demonstrated by the corkscrew-shaped bacterial flagellum. However, a symmetry analysis suggested that much simpler shapes are potentially also propulsive if they are rotated in a non-trivial way. This would have important implications as then a novel class of micro- and nanoswimmers with highly symmetric, and easier to fabricate shapes, become feasible. Here, the propulsion characteristics of V-shaped objects that are driven by means of an external torque are investigated. The torque was either exerted by an external magnetic or an electric field and the ”V”-shaped particle had a corresponding dipole moment. Experiments with macroscopic as well as microscopic rigid bodies revealed that the orientation of the dipole with respect to the body plays a crucial role for their ability to convert a rotation into a translation. Symmetry arguments are developed, which accurately predict whether or not the object is propulsive at all, and additionally if it moves uni- or bi-directionally. It is thereby unequivocally shown by theory and experimental evidence that chirality is not a prerequisite for efficient rotation-translation coupling at low Re but that propulsive objects are necessarily chiral if they are driven magnetically. Surprisingly, rotation of a truly achiral object will also lead to a propulsion, which is experimentally demonstrated for the first time utilizing an electrically driven ”V”-shaped particle. Because chirality, i.e. Pb-odd symmetry, is not a requirement, an extended analysis that also includes the object’s symmetry under charge conjugation (CÒ) is employed to explain and predict the correct propulsion characteristics of arbitrary shaped objects by means of rotation-translation coupling.
In contrast, spherical objects are unable to utilize rotation-translation coupling. However, beads with unequal chemical reactivities on the two ”faces” of their spherical body, so called Janus particles, can show enhanced diffusion if a suitable chemical substrate is provided. A catalytic reaction converts the intrinsic asymmetry of the particles into a pressure gradient, which leads to a self-generated motion. Most reports of self-propulsion to date concern larger microparticles. In this thesis, it is examined if this means of propulsion can also be realized in sub-micron sized Janus particles. The exact propul-sion characteristics are not fully clear in most chemically-driven particles and how their enhanced diffusion scales with size. Because of their small size the observation of individual particles is not possible and thus high density particle ensembles are observed by light scattering techniques, i.e. Dynamic Light Scattering (DLS), Differential Dynamic Microscopy (DDM) and Super-Heterodyne Laser Doppler Velocimetry (SH-LDV). In contrast to DLS and DDM, SH-LDV is identified as a versatile and suitable technique for the characterisation of active motion exhibited by Janus nanoparticles. First results on their size-dependent enhanced diffusion are presented, which show that this form of symmetry-breaking is effective at the smallest of scales.
The second part of this thesis considers the spectroscopic response exhibited by chiral and achiral shaped nanoparticles measured in a novel single-particle spectrometer. It is based on dark-field microscopy and contains a balanced detection setup, which was built to record the Circular Differential Scattering Intensity (CDSI) of a single nanoparticle, i.e. the difference in scattering intensities for left- and right-circularly polarized light. This is known as chiroptical spectroscopy and typical setups are limited to the examination of stationary single particles. However, problems arise as their spectra appear distorted owing to a fixed light-object symmetry as well as interactions with the surface to which the particles are adhere. In contrast, the approach employed in this thesis opens up the possibility to record chiroptical spectra in ”one shot” and hence observe single mobile nanoparticles away from a surface. Crucially, a freely suspended particle in a liquid randomly reorients due to Brownian motion, which leads to an isotropic sampling of all spatial orientations. Based on this principle, this work presents time-resolved spectroscopic observations that yield snapshots for a particular alignment during the re-orientation of the particle, and the average of the time-series of snapshots provides a true chiroptical spectrum of a single nanoparticle in bulk solution away from a surface. Remarkably, this is the first time that the chiroptical spectrum of a freely diffusing nanoparticle has been observed. Experiments confirm that the novel approach detects intrinsic chirality of a single nanoparticle and additionally it is shown how even achiral particles can exhibit apparent chirality for stationary orientations. A magnetic and plasmonic nanohelix, whose alignment is controlled in an external magnetic field validates the crucial dependence of the chiroptical spectra on the light-object symmetry. Finally, the ergodicity of this chiroptical spectroscopy is demonstrated by showing the equality between time-averaged single-particle and traditional ensemble-averaged spectra. This has important consequences as now the same information de-duced by typical measurements conducted on many particles in a cuvette is recovered by utilizing only one nanoparticle. The results presented herein show that the single-particle spectrometer is a promising platform for novel sensing applications.
Evaluation of nanorobots for targeted delivery into the retina
Schnichels, S., Goyal, R., Hurst, F., Ziemsen, F., Qiu, T., Fischer, P.
61, pages: 1355, Investigative Ophthalmology & Visual Science,The Association for Research in Vision and Ophthalmology, June 2020 (conference)
A major challenge in the treatment of eye diseases in general and retinal diseases in particular, is to deliver drugs to their target sites. Traditional intravitreal injection is based on random, passive diffusion of molecules. In order to specifically address certain structures of the retina, the use of novel particles from biomaterial research promises a more targeted application. The major challenge for such particles is the narrow macromolecular matrix of ocular tissue (including the vitreous body), which acts as a barrier and prevents the penetration of particles. Novel nanorobots from material research - more precisely: nanopropellers - that can be actively controlled through the vitreous body to reach the retina present a chance to reach desired targets in the retina.
Acoustofluidic Tweezers for the 3D Manipulation of Microparticles
Guo, X., Ma, Z., Goyal, R., Jeong, M., Pang, W., Fischer, P., Dian, X., Qiu, T.
2020 IEEE International Conference on Robotics and Automation (ICRA 2020), pages: 11392-11397, IEEE, Piscataway, NJ, IEEE International Conference on Robotics and Automation (ICRA 2020), 2020 (conference)
Non-contact manipulation is of great importance in the actuation of micro-robotics. It is challenging to contactless manipulate micro-scale objects over large spatial distance in fluid. Here, we describe a novel approach for the dynamic position control of microparticles in three-dimensional (3D) space, based on high-speed acoustic streaming generated by a micro-fabricated gigahertz transducer. Due to the vertical lifting force and the horizontal centripetal force generated by the streaming, microparticles are able to be stably trapped at a position far away from the transducer surface, and to be manipulated over centimeter distance in all three directions. Only the hydrodynamic force is utilized in the system for particle manipulation, making it a versatile tool regardless the material properties of the trapped particle. The system shows high reliability and manipulation velocity, revealing its potentials for the applications in robotics and automation at small scales.
Soft Microrobots Based on Photoresponsive Materials
In Mechanically Responsive Materials for Soft Robotics, pages: 327-362, (Editors: Koshima, Hideko), Wiley-VCH, Weinheim, 2020 (incollection)
2019
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)
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.
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)
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.
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)
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.
The acoustic hologram and particle manipulation with structured acoustic fields
Karlsruher Institut für Technologie (KIT), May 2019 (phdthesis)
This thesis presents holograms as a novel approach to create arbitrary ultrasound fields. It is shown how any wavefront can simply be encoded in the thickness profile of a phase plate. Contemporary 3D-printers enable fabrication of structured surfaces with feature sizes corresponding to wavelengths of ultrasound up to 7.5 MHz in water—covering the majority of medical and industrial applications. The whole workflow for designing and creating acoustic holograms has been developed and is presented in this thesis. To reconstruct the encoded fields a single transducer element is sufficient. Arbitrary fields are demonstrated in transmission and reflection configurations in water and air and validated by extensive hydrophone scans. To complement these time-consuming measurements a new approach, based on thermography, is presented, which enables volumetric sound field scans in just a few seconds. Several original experiments demonstrate the advantages of using acoustic holograms for particle manipulation. Most notably, directed parallel assembly of microparticles in the shape of a projected acoustic image has been shown and extended to a fabrication method by fusing the particles in a polymerization reaction. Further, seemingly dynamic propulsion from a static hologram is demonstrated by controlling the phase gradient along a projected track. The necessary complexity to create ultrasound fields with set amplitude and phase distributions is easily managed using acoustic holograms. The acoustic hologram is a simple and cost-effective tool for shaping ultrasound fields with high-fidelity. It is expected to have an impact in many applications where ultrasound is employed.
Dynamics of self-propelled colloids and their application as active matter
University of Groningen, Zernike Institute for Advanced Materials, 2019 (phdthesis)
In this thesis, the behavior of active particles spanning from single particle dynamics to collective behavior of many particles is explored. Active colloids are out-of equilibrium systems that have been studied extensively over the past 15 years. This thesis addresses several phenomena that arise in the field of active colloids.
2018
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, Piscataway, NJ, USA, International Conference on Intelligent Robots and Systems 2018, October 2018 (inproceedings)
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.
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)
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.
Colloidal Chemical Nanomotors
Colloidal Chemical Nanomotors, Cuvillier Verlag, Univ. of Stuttgart, June 2018 (phdthesis)
Synthetic sophisticated nanostructures represent a fundamental building block for the development of nanotechnology. The fabrication of nanoparticles complex in structure and material composition is key to build nanomachines that can operate as man-made nanoscale motors, which autonomously convert external energy into motion.
To achieve this, asymmetric nanoparticles were fabricated combining a physical vapor deposition technique known as NanoGLAD and wet chemical synthesis.
This thesis primarily concerns three complex colloidal systems that have been developed:
i)Hollow nanocup inclusion complexes that have a single Au nanoparticle in their pocket. The Au particle can be released with an external trigger.
ii)The smallest self-propelling nanocolloids that have been made to date, which give rise to a local concentration gradient that causes enhanced diffusion of the particles.
iii)Enzyme-powered pumps that have been assembled using bacteriophages as biological nanoscaffolds. This construct also can be used for enzyme recovery after heterogeneous catalysis.
Soft Miniaturized Linear Actuators Wirelessly Powered by Rotating Permanent Magnets
Qiu, T., Palagi, S., Sachs, J., Fischer, P.
In 2018 IEEE International Conference on Robotics and Automation (ICRA), 2018 IEEE International Conference on Robotics and Automation (ICRA), pages: 3595-3600, Piscataway, NJ, USA, May 2018 (inproceedings)
Wireless actuation by magnetic fields allows for the operation of untethered miniaturized devices, e.g. in biomedical applications. Nevertheless, generating large controlled forces over relatively large distances is challenging. Magnetic torques are easier to generate and control, but they are not always suitable for the tasks at hand. Moreover, strong magnetic fields are required to generate a sufficient torque, which are difficult to achieve with electromagnets. Here, we demonstrate a soft miniaturized actuator that transforms an externally applied magnetic torque into a controlled linear force. We report the design, fabrication and characterization of both the actuator and the magnetic field generator. We show that the magnet assembly, which is based on a set of rotating permanent magnets, can generate strong controlled oscillating fields over a relatively large workspace. The actuator, which is 3D-printed, can lift a load of more than 40 times its weight. Finally, we show that the actuator can be further miniaturized, paving the way towards strong, wirelessly powered microactuators.
Nanorobots propel through the eye
Wu, Z., Troll, J., Jeong, H., Qiang, W., Stang, M., Ziemssen, F., Wang, Z., Dong, M., Schnichels, S., Qiu, T., Fischer, P.
Max Planck Society, 2018 (mpi_year_book)
Scientists at the Max Planck Institute for Intelligent Systems in Stuttgart developed specially coated nanometer-sized robots that could be moved actively through dense tissue like the vitreous of the eye. So far, the transport of such nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. Our work constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.
2017
Locomotion of light-driven soft microrobots through a hydrogel via local melting
Palagi, S., Mark, A. G., Melde, K., Qiu, T., Zeng, H., Parmeggiani, C., Martella, D., Wiersma, D. S., Fischer, P.
In 2017 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), pages: 1-5, Piscataway, NJ, USA, July 2017 (inproceedings)
Soft mobile microrobots whose deformation can be directly controlled by an external field can adapt to move in different environments. This is the case for the light-driven microrobots based on liquid-crystal elastomers (LCEs). Here we show that the soft microrobots can move through an agarose hydrogel by means of light-controlled travelling-wave motions. This is achieved by exploiting the inherent rise of the LCE temperature above the melting temperature of the agarose gel, which facilitates penetration of the microrobot through the hydrogel. The locomotion performance is investigated as a function of the travelling-wave parameters, showing that effective propulsion can be obtained by adapting the generated motion to the specific environmental conditions.
Programmable chiral nanocolloids
EPFL, July 2017 (phdthesis)
Nanoparticles promise a variety of application in energy, medicine, and biology. However, most nanoparticles’ material composition and shape cannot be tuned and so functions have thus far been limited. Moreover they are often also chemically unstable in solution. Therefore, the overall goal of this thesis is to develop nanoparticles whose function and shape can be programmed and that can be corrosion protected, and to then apply these nanoparticles to sensing tasks in complex biological fluids. A special focus of this thesis is chiral nanostructures. A promising technique to address this is physical vapour shadow growth, namely nano glancing angle deposition (nanoGLAD). This scheme allows the design of new three-dimensional (3D) hybrid nanoparticles as it permits the control over both the shape and material composition of the nanoparticles. Although this method offers the possibility to grow nanoparticles that are functionally programmed, it has so far not allowed the use of many materials that are chemically unstable in solution, which limits the scope of potential applications.
This thesis starts with describing the nanoGLAD growth procedure. A first application is the wafer-scale patterning of unconventional nanoshapes, e.g. tri-layer particles, holes, rings, and hollow domes, which are not possible using state of the art 3D nanofabrication methods (chapter 2). Then, in conjunction with atomic layer deposition (ALD), this thesis shows how the nanoGLAD scheme can be adapted for the fabrication of ‘3D core-shell nanoparticles and nanocolloids’ using unstable and reactive materials. The key concept here is that the core consists of the unstable material which is grown such that the shell contains no voids or defects (chapter 3). Notably, the shapes that can be grown include symmetry-broken chiral nanoparticles, which possess unique spectral properties that make them useful for sensing applications. This thesis uses chiral nanocolloids to realise extremely sensitive plasmonic nanosensors and nanocolloids that can also be used as a nanomechanical probes for active nanorheology. By forming a composite of two materials during growth – one that gives a strong plasmonic response and the other to tune the composite’s dielectric function – plasmonic nanoparticles are presented that show record local surface plasmon resonance (LSPR) sensitivities to date (chapter 4). With the same alloying principle a plasmonic and a ferromagnetic material are combined. The resulting ‘chiral plasmonic ferromagnetic’ particles can be actuated using a magnetic field and this is used to measure the viscosity of blood plasma in the presence of blood cells. The viscosity of blood serum is an important disease indicator, but the measurement using commercial rheometers requires the separation of the blood cells. This is not needed in the nanorheological measurements shown in this thesis (chapter 5).
A Wirelessly Actuated Robotic Arm for Endoscopy
Qiu, T., Palagi, S., Adams, F., Wetterauer, U., Miernik, A., Fischer, P.
pages: 29, The Hamlyn Symposium on Medical Robotics, June 2017 (conference)
Endoscopy enables a number of important minimally invasive medical procedures. Current commercial flexible endoscopes with small diameter often have only one bending section near the tip with only one degree of freedom (DoF). This strongly limits the area that can be reached by the endoscope. Researchers have made many efforts to develop multi-DoF miniaturized robotic endoscopes that can be controlled in multiple bending sections and that still possess an overall size small enough to enter the body through a single-port [1]. Robotic endoscopes are normally actuated by tendons [2], pneumatics [3] or the rotation of concentric tubes [4]. In comparison to these tethered approaches, wireless actuation allows for more flexibility and easier miniaturization.
Ultrasound is a promising way to transfer power wirelessly in vivo. Recently, we reported an active surface actuator that directly converts ultrasound power into mechanical work via acoustic streaming from an array of micro-bubbles [5]. Here, we apply such wireless actuators to a miniaturized robotic arm, which works as an endoscopic tip (Fig. 1). The active surfaces consisting of arrays of micro-bubbles are attached to the arm and generate streaming of the adjacent fluid under ultrasound excitation. The recoil force actuates the arm. Different bubble sizes are addressed by different ultrasound frequencies, thus multiple DoFs are realized by the arm and require only one tunable ultrasound source.
Chapter 8 - Micro- and nanorobots in Newtonian and biological viscoelastic fluids
Palagi, S., (Walker) Schamel, D., Qiu, T., Fischer, P.
In Microbiorobotics, pages: 133 - 162, 8, Micro and Nano Technologies, Second edition, Elsevier, Boston, March 2017 (incollection)
Swimming microorganisms are a source of inspiration for small scale robots that are intended to operate in fluidic environments including complex biomedical fluids. Nature has devised swimming strategies that are effective at small scales and at low Reynolds number. These include the rotary corkscrew motion that, for instance, propels a flagellated bacterial cell, as well as the asymmetric beat of appendages that sperm cells or ciliated protozoa use to move through fluids. These mechanisms can overcome the reciprocity that governs the hydrodynamics at small scale. The complex molecular structure of biologically important fluids presents an additional challenge for the effective propulsion of microrobots. In this chapter it is shown how physical and chemical approaches are essential in realizing engineered abiotic micro- and nanorobots that can move in biomedically important environments. Interestingly, we also describe a microswimmer that is effective in biological viscoelastic fluids that does not have a natural analogue.
Wireless micro-robots for endoscopic applications in urology
Adams, F., Qiu, T., Mark, A. G., Melde, K., Palagi, S., Miernik, A., Fischer, P.
In Eur Urol Suppl, 16(3):e1914, March 2017 (inproceedings)
Endoscopy is an essential and common method for both diagnostics and therapy in Urology. Current flexible endoscope is normally cable-driven, thus it is hard to be miniaturized and its reachability is restricted as only one bending section near the tip with one degree of freedom (DoF) is allowed. Recent progresses in micro-robotics offer a unique opportunity for medical inspections in minimally invasive surgery. Micro-robots are active devices that has a feature size smaller than one millimeter and can normally be actuated and controlled wirelessly. Magnetically actuated micro-robots have been demonstrated to propel through biological fluids.Here, we report a novel micro robotic arm, which is actuated wirelessly by ultrasound. It works as a miniaturized endoscope with a side length of ~1 mm, which fits through the 3 Fr. tool channel of a cystoscope, and successfully performs an active cystoscopy in a rabbit bladder.
Akustische Hologramme steuern Partikel
Melde, K., Qiu, T., Mar, A., Fischer, P.
January 2017 (misc)
Hologramme sind vor allem im optischen Bereich zur Darstellung räumlicher Bilder bekannt. Das Prinzip lässt sich aber auf andere Wellenvorgänge übertragen. Das von unserer Gruppe am Max‐Planck‐Institut für Intelligente Systeme in Stuttgart entwickelte akustische Hologramm ist ein neues Bauelement, das Schallwellen in bisher unerreichter Komplexität und Auflösung formen kann [1]. Es funktioniert sowohl in Transmission als auch Reflexion und eignet sich besonders gut für Ultraschall.
2016
Soft continuous microrobots with multiple intrinsic degrees of freedom
Palagi, S., Mark, A. G., Melde, K., Zeng, H., Parmeggiani, C., Martella, D., Wiersma, D. S., Fischer, P.
In 2016 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), pages: 1-5, Piscataway, NJ, USA, July 2016 (inproceedings)
One of the main challenges in the development of microrobots, i.e. robots at the sub-millimeter scale, is the difficulty of adopting traditional solutions for power, control and, especially, actuation. As a result, most current microrobots are directly manipulated by external fields, and possess only a few passive degrees of freedom (DOFs). We have reported a strategy that enables embodiment, remote powering and control of a large number of DOFs in mobile soft microrobots. These consist of photo-responsive materials, such that the actuation of their soft continuous body can be selectively and dynamically controlled by structured light fields. Here we use finite-element modelling to evaluate the effective number of DOFs that are addressable in our microrobots. We also demonstrate that by this flexible approach different actuation patterns can be obtained, and thus different locomotion performances can be achieved within the very same microrobot. The reported results confirm the versatility of the proposed approach, which allows for easy application-specific optimization and online reconfiguration of the microrobot's behavior. Such versatility will enable advanced applications of robotics and automation at the micro scale.
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), pages: 1-5, Piscataway, NJ, USA, July 2016 (inproceedings)
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.
Auxetic Metamaterial Simplifies Soft Robot Design
Mark, A. G., Palagi, S., Qiu, T., Fischer, P.
In 2016 IEEE Int. Conf. on Robotics and Automation (ICRA), pages: 4951-4956, Piscataway, NJ, USA, May 2016 (inproceedings)
Soft materials are being adopted in robotics in order to facilitate biomedical applications and in order to achieve simpler and more capable robots. One route to simplification is to design the robot's body using `smart materials' that carry the burden of control and actuation. Metamaterials enable just such rational design of the material properties. Here we present a soft robot that exploits mechanical metamaterials for the intrinsic synchronization of two passive clutches which contact its travel surface. Doing so allows it to move through an enclosed passage with an inchworm motion propelled by a single actuator. Our soft robot consists of two 3D-printed metamaterials that implement auxetic and normal elastic properties. The design, fabrication and characterization of the metamaterials are described. In addition, a working soft robot is presented. Since the synchronization mechanism is a feature of the robot's material body, we believe that the proposed design will enable compliant and robust implementations that scale well with miniaturization.
Chiral Metamaterials
Univ. of Stuttgart, April 2016 (phdthesis)
Als Teil meiner Promotion habe ich die Effekte der Lichtabsorption mit zirkularer Polarisation auf kolloidalen Suspensionen und Beschichtungen untersucht, die als Anordnung spiralförmiger Nanopartikel auftreten, welche durch die Nutzung von plasmon aktive Metallen angeordnet werden. Wir haben gezeigt, dass diese Nanopartikel sehr ausgeprägte chirooptische Eigenschaften haben können. Mithilfe spezifischer Anordnungen verschiedener Metalle wie Gold, Silber und Kupfer können diese spektral justiert werden. Hierzu werden die geometrischen Formparameter der spiralförmigen Nanostrukturen der verwendeten Metalle angepasst. Des Weiteren habe ich das Zusammenspiel von Magnetismus und Plasmonen untersucht. Da die Streuung freier Elektronen und das ferromagnetische Feld in der selben größen ordnung liegen, wird der Eintritt interessanter Phänomene erwartet. Es ist mir gelungen, ein Metamaterial herzustellen, in dem zum ersten Mal die Präsenz eines magnetochiralen Dichroismus in Raumkonditionen nachgewiesen werden konnte. Das finale Ziel zukünftiger Forschungsprojekte in diesem Bereich wäre es festzustellen, ob die dünnen Filme plasmonischer Nanohelices dazu verwendet werden können, ein Metamaterial herzustellen, das einen negativen Brechungsindex für sichtbares Licht hat.
Towards Photo-Induced Swimming: Actuation of Liquid Crystalline Elastomer in Water
cerretti, G., Martella, D., Zeng, H., Parmeggiani, C., Palagi, S., Mark, A. G., Melde, K., Qiu, T., Fischer, P., Wiersma, D.
In Proc. of SPIE 9738, pages: Laser 3D Manufacturing III, 97380T, Bellingham, Washington, April 2016 (inproceedings)
Liquid Crystalline Elastomers (LCEs) are very promising smart materials that can be made sensitive to different external stimuli, such as heat, pH, humidity and light, by changing their chemical composition. In this paper we report the implementation of a nematically aligned LCE actuator able to undergo large light-induced deformations. We prove that this property is still present even when the actuator is submerged in fresh water. Thanks to the presence of azo-dye moieties, capable of going through a reversible trans-cis photo-isomerization, and by applying light with two different wavelengths we managed to control the bending of such actuator in the liquid environment. The reported results
represent the first step towards swimming microdevices powered by light.
Microdevices for Locomotion in Complex Biological Fluids
EPFL, 2016 (phdthesis)
Locomotion is an essential feature for survival of many organisms, and it is also a technical requirement for untethered biomedical microdevices to operate inside the human body for targeted drug delivery and minimally invasive surgery. The overall goal of this thesis is to develop microdevices that are capable of actively propelling themselves through and performing tasks in complex biological fluids. Two major challenges are encountered: the complex fluidic environment and the small length scale. The first part of the thesis addresses the first challenge: the diverse rheological properties of biological fluids. Most biological fluids are non-Newtonian, and to move in these fluids, the propulsion scheme is highly dependent on the size of the device: 1) When it is comparable or smaller than the mesh size of the biopolymeric network, then the device experiences purely viscous drag, thus the schemes for propulsion in Newtonian fluids will still be effective. To study the active microrheology of porous biological fluids, a magnetic tweezer set-up is constructed to pull magnetic beads of varying size through the porcine vitreous. It is found that for unhindered propulsion through the vitreous, nanodevices with a cross-section of less than 500 nm are needed. 2) When the size of the device is larger than the fluidic mesh size, non-Newtonian properties of the fluid become important and can be utilized for propulsion. We design the first symmetric micro-swimmer actuated by reciprocal motion and demonstrate its propulsion in biologically-relevant fluids. A larger scale low Reynolds number swimmer model is also built and excellent agreement between measurements and theory indicates that the net propulsion is caused by modulation of the fluid viscosity upon varying the shear rate. It opens new possibilities of using a simple actuation scheme for propulsion in non-Newtonian biological fluids. The second challenge is the small size of the device which severely limits the choice of available miniaturized actuators. We explore a novel wireless ultrasonic actuation scheme and a prototype is tested for application in the urinary tract. In order to test the prototype, a general technique is first developed to build a phantom of the human kidney. Based on high resolution medical imaging data, a three dimensional (3D) model is constructed using 3D printing and polymer casting techniques. The phantom not only faithfully reproduces the anatomical structural details, but also mimics the mechanical properties of the real tissue. To address the challenge of powering untethered microdevices, a novel bubble array streaming surface (BASS) actuator is developed. Under ultrasonic excitation, the oscillation of micro gas bubbles results in acoustic streaming and provides a propulsive force that drives the device. Ultrasonic actuators with different bubble sizes are fabricated, and individual driving frequency and propulsive force are measured. The actuator operates as an end-effector of a miniaturized endoscope, which has a cross-sectional side length of only 1 mm, thinner than the endoscopes currently in use. The tip of the end-effector is equipped with a miniaturized camera, its orientation is controlled wirelessly by the actuator, and active cystoscopy is successfully performed inside a rabbit bladder. Miniaturized medical instruments and micro-robots will benefit from the wireless actuation schemes demonstrated herein.
2015
3D-printed Soft Microrobot for Swimming in Biological Fluids
Qiu, T., Palagi, S., Fischer, P.
In Conf. Proc. IEEE Eng. Med. Biol. Soc., pages: 4922-4925, Piscataway, NJ, USA, August 2015 (inproceedings)
Microscopic artificial swimmers hold the potential to enable novel non-invasive medical procedures. In order to ease their translation towards real biomedical applications, simpler designs as well as cheaper yet more reliable materials and fabrication processes should be adopted, provided that the functionality of the microrobots can be kept. A simple single-hinge design could already enable microswimming in non-Newtonian fluids, which most bodily fluids are. Here, we address the fabrication of such single-hinge microrobots with a 3D-printed soft material. Firstly, a finite element model is developed to investigate the deformability of the 3D-printed microstructure under typical values of the actuating magnetic fields. Then the microstructures are fabricated by direct 3D-printing of a soft material and their swimming performances are evaluated. The speeds achieved with the 3D-printed microrobots are comparable to those obtained in previous work with complex fabrication procedures, thus showing great promise for 3D-printed microrobots to be operated in biological fluids.
2014
3D nanofabrication on complex seed shapes using glancing angle deposition
Hyeon-Ho, J., Mark, A. G., Gibbs, J. G., Reindl, T., Waizmann, U., Weis, J., Fischer, P.
In 2014 IEEE 27th International Conference on Micro Electro Mechanical Systems (MEMS), pages: 437-440, Piscataway, NJ, USA, January 2014 (inproceedings)
Three-dimensional (3D) fabrication techniques promise new device architectures and enable the integration of more components, but fabricating 3D nanostructures for device applications remains challenging. Recently, we have performed glancing angle deposition (GLAD) upon a nanoscale hexagonal seed array to create a variety of 3D nanoscale objects including multicomponent rods, helices, and zigzags [1]. Here, in an effort to generalize our technique, we present a step-by-step approach to grow 3D nanostructures on more complex nanoseed shapes and configurations than before. This approach allows us to create 3D nanostructures on nanoseeds regardless of seed sizes and shapes.
Active Microrheology of the Vitreous of the Eye applied to Nanorobot Propulsion
Qiu, T., Schamel, D., Mark, A. G., Fischer, P.
In 2014 IEEE INTERNATIONAL CONFERENCE ON ROBOTICS AND AUTOMATION (ICRA), pages: 3801-3806, IEEE International Conference on Robotics and Automation ICRA, Piscataway, NJ, USA, 2014, Best Automation Paper Award – Finalist. (inproceedings)
Biomedical applications of micro or nanorobots require active movement through complex biological fluids. These are generally non-Newtonian (viscoelastic) fluids that are characterized by complicated networks of macromolecules that have size-dependent rheological properties. It has been suggested that an untethered microrobot could assist in retinal surgical procedures. To do this it must navigate the vitreous humor, a hydrated double network of collagen fibrils and high molecular-weight, polyanionic hyaluronan macromolecules. Here, we examine the characteristic size that potential robots must have to traverse vitreous relatively unhindered. We have constructed magnetic tweezers that provide a large gradient of up to 320 T/m to pull sub-micron paramagnetic beads through biological fluids. A novel two-step electrical discharge machining (EDM) approach is used to construct the tips of the magnetic tweezers with a resolution of 30 mu m and high aspect ratio of similar to 17:1 that restricts the magnetic field gradient to the plane of observation. We report measurements on porcine vitreous. In agreement with structural data and passive Brownian diffusion studies we find that the unhindered active propulsion through the eye calls for nanorobots with cross-sections of less than 500 nm.
Best Automation Paper Award – Finalist.
2006
NONLINEAR OPTICAL PROPERTIES OF CHIRAL LIQUIDS Electric-dipolar pseudoscalars in nonlinear optics
Fischer, P., Champagne, B.
In NON-LINEAR OPTICAL PROPERTIES OF MATTER: FROM MOLECULES TO CONDENSED PHASES, 1, pages: 359-381, Challenges and Advances in Computational Chemistry and Physics, 2006 (incollection)
We give all overview of linear and nonlinear optical processes that can be specific to chiral molecules in isotropic media. Specifically, we discuss the pseudoscalars that underlie nonlinear optical activity and chiral frequency conversion processes in fluids. We show that nonlinear optical techniques open entirely new ways of exploring chirality: Sum-frequency-generation (SFG) at second-order and BioCARS at fourth-order arise in the electric-dipole approximation and do not require circularly polarized light to detect chiral molecules in solution. Here the frequency conversion in itself is a measure of chirality. This is in contrast to natural optical activity phenomena which are based on the interference of radiation from induced oscillating electric and magnetic dipoles, and which are observed as a differential response to right and left circularly polarized light. We give examples from our SFG experiments in optically active solutions and show how the application of an additional static electric field to sum-frequency generation allows the absolute configuration of the chiral solute to be determined via all electric-dipolar process. Results from ab initio calculations of the SFG pseudoscalar are presented for a number of chiral molecules